S21 all

Mortality Attributable to tobacco ndash

A Global Report

E Tursan drsquoEspaignet

Tobacco Free Initiative

WHO Geneva

tursandespaignetwhoint

WHO Global Report Mortality Attributable

to Tobacco

Estimates for high low and middle income countries

Effects of direct use of smoking (and smokeless) tobacco among adults aged 30+ for communicable and non-communicable diseases

Contents of the Report

Builds on global estimates

for 2004 provided in WHO

Report ldquoGlobal Health

Risks Mortality and

burden of disease

attributable to selected

major risksrdquo 2009

Expansion to provide data

at WHO Regional and

country levels

The global burden of tobacco use

Tobacco is the only legal drug that kills many of its users when used exactly as intended by manufacturers

Tobacco kills ndash Direct tobacco smoking 5 million people year

ndash Second hand smoke 600000 people year

ndash More than tuberculosis HIVAIDS and malaria combined

If effective measures are not urgently taken tobacco could in the 21st century kill over 1 billion people

999999999 + 1


Use of tobacco among adults in developing

countries is increasing

Accelerating rates of tobacco among women

Significant social and economic handicap for

families communities and governments

Contributes to family poverty

Global Voluntary NCD Targets for 2025

under consideration by Member States

Relative reduction in current tobacco smoking by

40 by 2025

Relative reduction in age-standardised death rate

from non-communicable diseases by 25

(using 2010 as baseline)

Surveillance of tobacco

Art 20 of the WHO FCTC requires parties to adopt standard methods of data collection to measure magnitude patterns determinants and consequences of tobacco use and exposure

Much of WHO activities until now has been on measuring the magnitude of the problem through youth and adult surveys

WHO is now also monitoring outcomes - Mortality report - Pregnancy report (mid-late 2012)

Method of calculating mortality

attributable to tobacco

The Population Attributable Fraction (PAF) method is

the proportion of deaths that may be attributed to

exposure to tobacco (or any other risk factor)

The PAF formula is made up of two factors

ndash The prevalence (P) of tobacco use in the population

ndash The relative risk (RR) of developing a disease among those

who smoke or consume smokeless tobacco compared with

those who do not use tobacco

The Smoking Impact Ratio (SIR) method

To estimate the excess mortality from lung cancer in

smokers in a countryrsquos population relative to the excess

mortality in smokers in the reference population

The resulting SIR estimate is then used instead of P in

the PAF formula

bull- CLC and NLC are lung cancer rates in the population and in

never smokers in a countryrsquos population

- SLC and NLC are lung cancer rates in smokers and never

smokers of the reference population

Causes of death are categorised into

3 broad groups

Group 1 Communicable diseases - Tuberculosis - Lower respiratory tract infection

Group 2 Non-communicable diseases - Cancers Lung cancer - Cardiovascular diseases Heart disease Stroke - Respiratory diseases ndash Chronic Obstructive Pulmonary Disease

Does not include Group 3 Injuries (external causes)

Report Layout

Report Layout

Major Findings

In 2004 about 5 million adults aged 30 years and

over died from direct tobacco use (smoking and

smokeless) around the globe 1 DEATH EVERY

6 SECONDS

12 of all 30+ deaths attributed to tobacco

Mortality higher among men than among women

Findings

Source WHO Global Report Mortality Attributable to Tobacco 2012

httpwwwwhointtobaccopublicationssurveillancerep_mortality_attributable_tobaccoeni

ndexhtml

Communicable disease findings

5 of all deaths from communicable diseases

7 of all deaths due to tuberculosis

12 of deaths due to lower respiratory infections

NCD Findings

NCDs account for 14 of all deaths are attributed to tobacco

Cardiovascular diseases 10

Of those adults aged 30-44 years who died from ischemic heart

disease 38 of the deaths were attributable to tobacco

Cancer deaths 22

71 of all lung cancer deaths are attributable to tobacco use

Respiratory diseases 36

42 of all chronic obstructive pulmonary disease are attributable to

tobacco use

Thank you for your attention

Stages of the Cigarette Epidemic

on Entering Its Second Century

Michael Thun

Richard Peto

Jillian Boreham

Alan Lopez

WCTOH

Singapore

March 2012

Full article in 20th Anniversary Edition

of Tobacco Control

20122196-101

Original WHO Model

Four Stages of the Cigarette Epidemic

Source Lopez et al Tobacco Control 1994

Value of this Model

bull Portrays epidemic as a continuum rather than as a

series of isolated events

bull Allows each country to find itself on this continuum

bull Communicates the long delay between the uptake

of widespread smoking and the full eventual

consequences for mortality

bull Indicates the paradoxical period in which

prevalence falls but mortality continues to increase

bull Shows that without effective tobacco control the

problem will get much worse

Disadvantages of original model

bull Based on the experience in

economically developed countries

bull No corresponding model could be

proposed for developing countries

bull The staging criteria based on the

comparative levels of smoking amp

mortality in men and women

bull Clearly not applicable in China or India

Methods

bull Assess trends in smoking-attributed mortality

by sex in 41 developed countries from 1950-

rdquopresentrdquo using Peto-Lopez indirect method

bull Emphasize ages 35-69

bull Review data on smoking prevalence in GATS

amp GYTS

bull Assess applicability of the model in countries

at various levels of economic development

bull Project the trends in prevalence amp smoking-

attributed mortality forward through 2025

Results

1 The original model still provides a

reasonably useful description of the

epidemic in many developed

countries

bull Prevalence has decreased in both sexes

although more slowly than predicted

bull Smoking-attributed deaths are decreasing in

men but increasing or have reached a plateau

in women

Male and female smoking prevalence

have converged at younger ages in

most high resource countries (amp have

crossed over at all ages in Sweden)

Trends in smoking-attributed deaths in

four high resource countries 1950-2005

US

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Australia

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Netherlands

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

UK

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Percent indicates percentage of all deaths attributed to smoking in age range 35-69

However the staging system in original

model does not fit China or India


Solution

bull Allow the stage of the epidemic to differ in

men and women

bull Designate these stages based on sex-

specific data

Evolution of the Smoking Epidemic

in Men

0

10

20

30

40

50

60

70

0 10 20 30 40 50 60 70 80 90 100 110 120

0

5

10

15

20

25

30

35

40

of deaths caused by

smoking

of smokers among adults

STAGE 1 STAGE 2 STAGE 3 STAGE 4

male smokers

male deaths

Sub-Saharan Africa

Southeast Asia

China Norway

Greece Latin American

Western Europe USA UK Australia


in Women

0

10

20

30

40

50

60

70

0 10 20 30 40 50 60 70 80 90 100 110 120

0

5

10

15

20

25

30

35

40

of deaths caused by

smoking of smokers among adults


female smokers

female deaths

Sub-Saharan Africa

Southeast Asia China

Eastern and Southern

Europe Western Europe USA UK

Australia

Conclusions

1 Predictions from the model fit well qualitatively

with recent trends in high resource countries

2 Also reasonably compatible with trends among

men in developing countries

3 The stages as defined by the original model are

not applicable to China or India

4 Modifying the model to allow different stages for

men and women will improve its generalizability

to developing countries

Thank You

Updated data on smoking-related

deaths in 41 countries available at

bull httptobaccocontrolbmjcomcontent212toc

bull httpwwwctsuoxacuk~tobacco

By 2030 7 of every 10 tobacco attributable deaths

projected to be in developing countries

Tobacco deaths 2000

Developed 2 million

Developing 2 million

The global burden of deaths from tobacco is

shifting from developed to developing

countries

Tobacco deaths 2030

3 million

7 million

World Health Organization 1999 Making a Difference World Health Report 1999 Geneva Switzerland

Smoking-attributed mortality estimates

in original model based on US data

0

10

20

30

40

50

60

70

0 10 20 30 40 50 60 70 80 90 100

0

5

10

15

20

25

30

35

40

of deaths caused by

smoking



19601900 1920 1940 1980 2000

male smokers

female smokers

male deaths

female deaths

US data updated to most recent year available

Prevalence through 2010 Smoking-Attributed Mortality

through 2005

Trends in Cigarette Smoking Prevalence ()

by Sex Adults 18 and Older US 1965-2010

0

10

20

30

40

50

60

1965

1974

1979

1983

1985

1990

1992

1994

1995

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

2009

2010

Year

Pre

vale

nce (

)

Source National Health Interview Survey 1965-2010 National Center for Health Statistics Centers for Disease

Control and Prevention 2011

Men

Women

(52)

(34) (215)

(173)

Prevalence of smoking - UK Men

0

10

20

30

40

50

60

70

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Women

0

10

20

30

40

50

60

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Pre

vale

nce

Source IMASS v4 2010

Australia

Men

0

10

20

30

40

50

60

70

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Women

0

10

20

30

40

50

60

70

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Pre

vale

nce


Epidemic lags in women in all Southern

and most Eastern European countries

Romania

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Greece

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Poland

0

5

10

15

20

25

30

35

40

45

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Russia

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Trends in lung cancer death rates

among men in US UK and Commonwealth

United Kingdom

United States

Canada

New Zealand

Australia

Lung cancer mortality age 35-69

for selected countries 1960-2000

UK US France Hungary

Peto R Lopez AD et al httpwwwctsuoxacuk~tobaccoindexhtm

Trends in lung cancer death rates among

men in Southern Europe

Greece

Italy

Spain

Source Li et al (2011) NEJM Vol 36425

Active Smoking Secondhand Smoke and Breast Cancer Risk

Kenneth C Johnson PhD

Department of Epidemiology and

Community Medicine

Faculty of Medicine

University of Ottawa

March 23 2012

World Conference on Tobacco or Health

Singapore

Overview

Passive smoking meta-analyses

3 Interpretations 2004 2005 2006

Canadian Expert Panel 2009

Active smoking risk

Conclusions

Passive smoking

Secondhand smoke

Involuntary smoking

Environmental tobacco smoke (ETS)

Expert Panel Approach

Based on the weight of evidence from

- epidemiologic studies

- toxicological studies and

- understanding of biological mechanisms

What can be concluded about the relationships between

- passive smoking and breast cancer

- active smoking and breast cancer

20 Mammary Carcinogens in SHS

Acrylamide

Acrylonitrile

13-Butadiene

Isoprene

Nitromethane

Propylene Oxide

Dibenz[ah]anthracene

Vinyl chloride

4-Aminobiphenyl

Urethane

Benzene

Nitrobenzene

Benzo[a]pyrene

ortho-Toluidine

Dibenzo[ae]pyrene

Dibenzo[ai]pyrene

Dibenzo[al]pyrene

N-Nitrosodiethylamine

N-Nitrosodi-n-butylamine

Undiluted Sidestream Tobacco

Smoke versus Mainstream Smoke

Examples Ratio in Sidestream to

Mainstream Smoke

- Carbon monoxide

- Nitrogen Oxides

- Nicotine

25-15 times as much

37-128 times

13-21 as much

- Benzene

- Formaldehyde

- NNK

- Benz(a)pyrene

- Nickel

- Tar

8-10 times as much

50 times as much

1-22 times as much

25-20 times as much

13-30 times as much

11-157 times

Source Hoffmann and Hecht 1989

bull 20 Studies published by end of 2004

bull 8 cohort studies 12 case control studies

bull 7 in Asia 3 in Europe 10 in North America

bull 9 before 2000 11 since 2000

bull Disease endpoint (18 diagnosis 2 death)

bull Significant age restrictions in 7 studies

bull Control for potential confounders in most studies

Meta-analysis of Studies of Passive

Smoking and Breast Cancer

Reference Johnson KC Accumulating Evidence on Passive and

Active Smoking and Breast Cancer Risk Int J Cancer May 2005

01

1

10H

iray

am

a 199

2W

arte

nb

erg

et

al

200

0R

eyn

old

s e

t a

l 20

04

Ha

nao

ka e

t al

200

4S

an

dle

r e

t al 1

985

Millik

an

et

al 1

998

De

lfin

o e

t al

2000

Scru

bso

le e

t al

2004

Gam

mon

et a

l 200

4S

mit

h e

t al

1994

Mo

rab

ia e

t al 1

996

Zh

ao

et

al

1999

Jo

hn

so

n e

t al

200

0K

ro

pp

et

al

200

2L

isso

wsk

a e

t al 2

00

6M

issed

Ex

po

su

re -

Co

ho

rt

Stu

die

s

Mis

sed

Ex

po

su

re -

Cas

e-C

on

tro

l

Be

tte

r E

xp

osu

re

Asses

sm

en

t

Relative risk (95 CI)

Studies of Passive Smoking and Premenopausal Breast Cancer Risk

|______________________________________|

Studies unlikely to have missed important sources of

passive smoking exposure

|_____________________|

Cohort

|___________________________|

Case-control

Studies likely to have missed important sources of


Thank god A panel of experts



Conclusions ndash Cal EPA Report (2005)

Passive Smoking amp Breast Cancer

ldquoOverall the weight of evidence

(including toxicology of tobacco

smoke constituents epidemiological

studies and breast biology) is

consistent with a causal association

between ETS exposure and breast

cancer in younger primarily

premenopausal womenrdquo


Thank god A panel of expertsThank god A panel of experts

Surgeon Generalrsquos Conclusion

ldquo The evidence is suggestive but not

sufficient to infer a causal relationship

between secondhand smoke and breast

cancerrdquo

California EPA and Surgeon General

found similar passive risk estimates California EPA Report

2005 1

Surgeon Generals

Report 20062

Exposure n Relative Risk

(95 CI)

N Relative Risk

(95 CI)

All studies 19 125 (108-144) 21 120 (108-135)

Premenopausal

Women lt 50

14 168 (131-215) 11 164 (125-214)

Premenopausal

with lifetime

exposure

assessment

5 220 (169-287) 6 185 (119-287)

A Question of Interpretation

Balancing Concerns

Results from Cohort Studies versus Case-control Studies

Exposure misclassification versus Recall and Response Bias

Confounding by Alcohol

Is the unexposed group different in other ways

Premenopausal risk and No Postmenopausal Risk

Passive but No Active Smoking Risk

Reference Rothman amp Greenland Modern Epidemiology 2nd

Ed

Studies of Excess Lung Cancer Risk for

Non-Smokers From Second-Hand Smoke

0

50

100

150

200

250

USA 1994

Europe 1998

Sweden 1998

Germany 1998

China 1999

Germany 2000

China 2000

Canada 2001

Excess Lung

Cancer Risk

(Percentage)

Spousal Home and Work -

Higher Exposure

Work Only -

Higher Exposure

Type and Level of Exposure

+1-25

+35-220 +50-210

SHS and Breast Cancer Studies since 2006

Lissowska et al (2007 2007b) lifetime SHS assessment

women under age 45 total SHS 100 136 152 202 (094-436)

Roddam et al (2007) spousal exposure only (41 exposed)

risk increases not found

Lin et al (2008) Japan Collaborative Cohort Study age 40-79 196 never smoker cases 8 ever smoker cases

no analyses with unexposed referent group

Pirie et al (2008) SHS age 0 10 current spousal (age 53-67) (11 exposed) risk increases not found

Pirie et al (2008) Meta-analysis retrospectiveprospective no subcategories

SHS and Breast Cancer Studies Since 2009 Ahern et al (2009) lifetime assessment

No consistent risk increases found

Reynolds et al (2010) California Teachers Cohort

ndash Updated evaluation of SHS

ndash Lifetime exposure assessment

Luo et al (2011) ndash Womenrsquos Health Initiative Cohort (US)

- Lifetime Exposure Assessment

Xue et al (2011) ndash Updated evaluation of the Harvard Nursesrsquo Health Cohort

- exposure assessment limited

- occupational assessment limited to current exposure in 1982

Secondhand Smoke and Breast

Cancer Risk ndash New Cohort Studies

SHS Exposure California

Teachers Cohort[48]

Adjusted HR

(95 CI)

Womenrsquos Health

Initiative Cohort[27]

Adjusted HR (95

CI)

No reported lifetime

exposure

100 100

Any childhood exposure 106 (094-119) 119 (093-153)

Any adult home exposure 104 (092-116) 091 (070-119)

Any workplace exposure 102 (093-113) 101 (082-126)

Highest cumulative lifetime

exposure (vs no lifetime

exposure from any source)

126 (099-160) 132(104-167)

Surgeon Generalrsquos Basic Premise

ldquoThere is substantial evidence that active

smoking is not associated with an

increased risk of breast cancer in studies

that compare active smokers with persons

who have never smokedrdquo

Surgeon Generalrsquos Report 2006 (p 446)

Surgeon General Relies Heavily on

53 Study Collaborative Reanalysis

ldquoIn a pooled analysis of data from 53 studies the

relative risk for women who were current smokers

versus life-time non-smokers was 099 (95 CI

092-105) for the 22225 cases and 40832 controls

who reported not drinking alcohol The effect of

smoking did not vary by menopausal statusrdquo


Overall risk for premenopausal

breast cancer and smoking ndash greater

than overall alcohol risk

Active smoking (non-drinkers) Relative Risk

current vs never 099 (092-105)

ever vs never 103 (098-107)

ever vs never premenopausal 107 (08-14)

Alcohol Relative Risk

ever vs never drinkers 106

Alcohol risk = 71 risk increase per drinkday

Increased Breast Cancer Risk with Active

Smoking in Recent Cohort Studies

Exposure

Study Measure Relative Risk (95 CI)

Cancer Prevention II 40+ years

40+ cigday

138 (105-183)

174 (115-262)

Nurses Health Study 15+ cigday 15 (11-20)

California Teachers 31 pack-yrs (premeno)

205 (120-349)

Canadian Breast Screening Cohort 40+ years and

gt20 cigday 183 (129-261)

NorwegianSwedish Cohort Study 20+ pack-yrs

Initiation 10-14 146 (111-193)

148 (103-213)

Japanese Public Health Center Ever active

(premeno) 39 (15-99)

References Calle et al 1994 Hunter et al 1997 Reynolds et al 2004 Terry et al 2002 Gram et al 2005

Hanaoka et al 2004

NAT2 Slow Acetylators NAT2 Rapid Acetylators

Premenopausal Postmenopausal Premenopausal Postmenopausal

Type of

Analysis

Pack-

years RR (95 CI) RR (95 CI) RR (95 CI) RR (95 CI)

Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)

Smoking Pack-years NAT2 Acetylators Status

Menopausal Status and Breast Cancer Risk

Source Ambrosone et al 2008



Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)

Pooled

Analysis

Never

active

100 100 100 100

lt20 105 (086-128) 123 (103-146) 091 (072-116) 110 (089-135)

gt20 149 (108-204) 142 (116-174) 129 (089-186) 088 (069-113)




Cohort Studies of Active Smoking and Breast Cancer Risk (gt500 cases) by Highest Exposure Categories

First author year Youngest age of

initiation

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137)

Al-Delaimy(2004) 129 (097-171)

Reynolds (2004) 117 (105-130)

Lawlor (2004)

Gram (2005) 148 (103-213)

Olson (2005) 112 (092-136)

Cui (2006) 111 (097-128)

Ha (2007) 148 (077-284)

8 of 8 positive

4 of 8 Stat Sig

Source Canadian Expert Panel on Tobacco Smoke and Breast Cancer Risk 2009

Cohort Studies of Active Smoking and Breast Cancer Risk by Highest Exposure Categories


initiation

Longest duration

before pregnancy

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131)

Al-Delaimy(2004) 129 (097-171) 110 (080-152)

Reynolds (2004) 117 (105-130) 113 (100-125)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137)

Olson (2005) 112 (092-136) 121 (101-125)

Cui (2006) 111 (097-128) 113 (101-125)

Ha (2007) 148 (077-284) 178 (127-249)11

9 of 9 positive

4 of 9 Stat Sig




initiation

Longest duration

before pregnancy

Longest

duration

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189)

Ha (2007) 148 (077-284) 178 (127-249)11

6 of 6 positive

3 of 6 Stat Sig




initiation

Longest duration

Before pregnancy

Longest

duration

Highest pack-

years

Calle (1994) 159 (117-215) 138 (105-183)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133) 125 (106-147)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174) 146 (111-193)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138) 115 (096-137)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189) 117 (102-134)

Ha (2007) 148 (077-284) 178 (127-249)11


5 of 5 positive

4 of 5 statistically sig

Table 13 Cohort Studies ndash Age of Smoking

Initiation And Breast Cancer Risk

First Author Year

Earliest Age Smoking

Began Category Cutoff

Relative Risk

(95 CI)

Reynolds et al (2004) lt20 117 (105-130)

Olson et al (2005) lt19 112 (092-136)

Xue et al (2011) lt18 104 (099-111)

Cui et al (2006) lt16 111 (097-128)

Al-Delaimy et al (2004) lt15 129 (097-171)

Gram et al (2005) lt15 148 (103-213)

Ha et al (2007) lt15 148 (077-284)

US Radiologic Technologists Cohort

Smoking Before 1st Birth

Reference M Ha K Mabuchi A J Sigurdson D M Freedman M S Linet M M Doody and M Hauptmann

Smoking cigarettes before first childbirth and risk of breast cancer Am J Epidemiol 166 55-61 (2007)


Smoking After 1st Birth




Smoking Risk Before and After 1st Birth



Source Xue et al Cigarette smoking and the incidence of breast cancer Arch Intern Med 2011 171(2)125-133

Harvard Nurses Health Study Cohort

Smoking before First Birth and

Increased Breast Cancer Risk

Lung Cancer and Passive Smoking

Reference Wald et al BMJ 1986 293 1217-22

i

14 Studies of Passive Smoking and Lung Cancer

Causal connection established 1986

Cumulative Meta-analysis of Spousal ETS

Exposure and Lung Cancer Risk 1981-1999

Secondhand Smoke Conclusion

Based on the weight of evidence presented by

- the California EPA

- the Surgeon General and

- strong recent evidence of an active smoking- breast cancer risk

The Expert Panel concluded that

The relationship between secondhand smoke and breast cancer in younger primarily premenopausal women is consistent with causality

Active Smoking Conclusion






The relationships between active smoking and both pre- and postmenopausal breast cancer are consistent with causality

Tobacco Control 2011

Lung disease in relation to tobacco exposure

Ioana Munteanu Fl Mihaltan

ldquoMarius Nastardquo Institute of pneumology Bucharest Romania

bull Effects of cigarette smoke on the lung

bull History

bull Lung diseases


bull History

bull Lung disease

Europe - 650000 deaths year are attribute to smoking

THE MECHANISM OF INDUCED LUNG INJURY

TOBACCO SMOKE

OXIDE ALDEHYDES ACIDS AMMONIA

CILIARY CLEARANCE DISTURBANCE

OXIDANTS AROMATIC HYDROCARBONS NITROSAMINES

Pathology of the Lung European Respiratory Society Monograph Vol 39 2007E dited by W Timens and HH Popper

LOCAL IRRITATION OF THE RESPIRATORY EPITHELIUM INJURY CELL DEATH INFLUX OF NEUTROPHILS

RETENTION OF MUCUS AND TOXINS

GROWTH SIGNALS DESTRUCTION OF CHROMOSOME AND DNA EXPRESSION OF ONCOGENES

INFLAMMATION

INFECTION CARCINOGENESIS

COPD AND OTHER INFLAMMATORY LUNG DISEASES

LUNG CANCER

850-900 4000 chemicals 60 carcinogenic

Pulmonary disease in relation to smoking

bull Diseases in which smoking is directly involved and has negative effects on their evolution

ndash COPD

ndash Lung cancer

httpwwwcdcgovtobaccodata_statisticsfact_sheetshealth_effectseffects_cig_smoking

Risk of developing a disease caused by smoking

bull As compared to nonsmokers smoking is

estimated to increase the risk of

ndash men developing lung cancer by 23 times

ndash women developing lung cancer by 13 times and

ndash dying of chronic obstructive lung diseases (such as

chronic bronchitis and emphysema) by 12 to 13

times


bull Diseases whose evolution is worsened by smoking bull Chronic inflammatory diseases

Asthma Emphysema due to α1-antitrypsin deficiency Chronic bronchitis

bull Neoplasms Cavum tumors Tumors of the mouth Laryngeal tumors

bull Infectious Diseases Rhinitis pharyngitis pneumonia influenza tuberculosis

bull Interstitial lung Disease Pneumoconiosis idiopathic pulmonary fibrosis idiopathic interstitial pneumonia bronchiolitis


bull History

bull Lung disease

History In 1950 Prof R Doll began his studies on the role

of smoking as risk factor in lung cancer He published in the British Medical Journal his conclusions The risk of developing the disease increases in proportion to the amount smoked It may be 50 times as great among those who smoke 25 or more cigarettes a day as among non-smokers

In 1964 the Association of Surgeons of the US presents the first cause and effect relationship between smoking and lung cancer

bull 1992 Environmental Protection Agencys Respiratory Health Effects of Passive Smoking Lung Cancer and Other Disorders complete their research on ETS

bull ETS was included in class A carcinogens in the same category as asbestos benzene and radon

bull More than 3000 lung cancer deaths per year

were attributed to ETS

bull The US Surgeon General The lung cancer risk

for a nonsmoker whose spouse is a smoker is 20-30 higher

1981 Earliest evidence of the passive smoking involvement in lung cancer development Takeshi Hirayama (Japan)


bull History

bull Lung diseases

bull COPD

PATHOGENESIS AND PATHOPHYSIOLOGY OF LUNG LESIONS INDUCED BY TOBACCO

Cigarette smoke Oxidants

Inflammation in the airways and lung

Bronchial biopsies showed Chronic inflammatory changes with increased no of specific inflammatory cells Structural remodeling due to repeated injury and repair mechanisms

Int J Environ Res Public Health 2009

bull Prospective study All individuals free of COPD in 1996 were monitored for up to 14 years

bull The cumulative incidence of physician-diagnosed COPD over a lifetime adjusted for the competing risk of death was calculated

bull Results were stratified by sex socioeconomic status and a rural or urban setting

bull Findings

A total of 579 466 individuals were diagnosed with COPD by a physician over the study period

ndash The overall lifetime risk of physician-diagnosed COPD at age 80 years was 276

ndash Lifetime risk was higher in men than in women (297 vs 256)

ndash Individuals of lower socioeconomic status had an increased risk as compared to those of higher socioeconomic status (321 vs 230)

ndash The risk was higher in individuals who lived in a rural setting than in those who lived in an urban setting (324 vs 267)

bull Interpretation

bull About one in four individuals are likely to be diagnosed and receive medical attention for COPD during their lifetime Clinical evidence-based approaches public health

action and more research are needed to identify effective strategies to prevent COPD and ensure that those with the disease have the highest quality of life possible

Lifetime risk of developing chronic obstructive pulmonary disease Dr Andrea S Gershon 2010

Smoking Cessation Improvement in

Postbronchodilator FEV1 Decline

Anthonisen et al JAMA 1994272(19)1497-1505 Kanner et al Am J Med 1999106(4)410-416

Follow up (y)

Po

stb

ron

cho

dila

tor

FEV

1 L

24

25

26

27

28

29

Screen 2 1 2 3 4 5

Sustained Quitters

Continuous Smokers

Susceptible smokers develop significant lung function decline

The Lung Health Study (LHS) (N=5887) aged 35 to 60 years 5 years follow up

COPD

The exact role of smoking cessation on airway inflammation in patients with COPD remains unknown

Studies- Inflammation persists despite smoking cessation

EXPLANATION bullPersistence of an inflammatory trigger that maintains ongoing local inflammatory response bullIn COPD persistent inflammation may be due to destruction of tissue in the airways induced by smoking

NEW HYPOTHESES - COPD may have an autoimmune component contributing to persistent inflammation even after smoking cessation


Predictors of Mortality in Patients with Stable COPD Esteban 2008

Five-year prospective cohort study

600 stable COPD patients recruited consecutively

Which clinical factors are associated with mortality in patients with stable COPD

bull Asthma

Asthma

Eur Respir J 2004 24 822ndash833

smoking is a risk candidate for development of asthma

smoking is more prevalent in individuals with asthma than in those without

smoking is associated with decreased asthma control and increased risk of mortality and asthma attacks and exacerbations

smokers with and without asthma may have different risk factors for smoking onset as well as different smoking motives and outcome expectancies

smoking cessation is associated with improvements in lung functioning and asthma symptoms

Effects of smoking cessation on airflow obstruction and quality of life in asthmatic smokers Jang ASKorea 2010

32 subjects

22 continue to smoke

10 quit smoking

Lung cancer

The lung cancer risks of smoking vary with the quantitative aspects of smoking

bull Duration of smoking is the stronger

determinant of lung cancer risk in some

analyses ( Doll and Peto)

bull Starting age is linked to duration of smoking

bull Depth of inhalation

bull Number of cigarettes smoked

bull Years as nonsmoker

bull The cigarette type

THE LUNG CANCER RISK INCREASEs EXPONENTIALLY WITH THE NUMBER OF YEARS

AND THE NUMBER OF CIGARETTE SMOKED BY DAY

Lubin J H Caporaso N E Cancer Epidemiol Biomarkers Prev

200615517-523

Lung Cancer in Patients with Chronic Obstructive Pulmonary Disease Incidence and Predicting Factors

Juan P de Torres Am J Respir Crit Care Med October 15 2011

bull A cohort of 2507 patients without initial clinical or radiologic evidence of lung cancer was monitored over a period of 60 months on average (30ndash90)

bull 215 patients with COPD developed lung cancer (incidence density of 167 cases per 1000 person-years)

bull Squamous cell carcinoma is the most frequent histologic type

bull Older patients with milder airflow obstruction (GOLD I and II) and lower body mass index

bull Lung cancer incidence was lower in patients with worse severity of airflow obstruction

Tobacco-attributable cancer burden in the UK in 2010 DM Parkin

2010 patients with stage IIIBIV NSCLC between June 2003 and March 2006

Pack-Years of Cigarette Smoking as a Prognostic Factor in Patients With Stage IIIBIV Nonsmall Cell Lung Cancer Janjigian Cancer 2010

Infectious diseases - tuberculosis

The association between smoking and tuberculosis has been investigated since 1918

Int J Tuberc Lung Dis 2007 Mar11(3)258-62 Associations between tobacco and tuberculosis

The reduction of tuberculosis risks by smoking cessation

Wen et al--2010

Smoking and mortality from tuberculosis and other diseases in India retrospective study of 43 000 adult male deaths and 35 000 controls

Gajalakshmi et al--2009

Tobacco smoking and pulmonary tuberculosis

Kolappan Gopi--2002

Thank you

Genetic and Lifestyle Modifiers of Smoking on Disease Risk

Woon-Puay Koh Saw Swee Hock School of Public Health

National University of Singapore

Cancer

List of cancers associated with cigarette smokinghelliphelliphellip

Lung

Mouth and pharynx

Larynx

Esophagus

Stomach

Pancreas

Liver

Cervix

Bladder

Kidney

Colorectum

Breast

Do all smokers get cancer

What modifies a smokerrsquos risk of cancer

Risk of lung cancer in smokers

Body mass index

Risk of colorectal cancer in smokers

Genetic polymorphism

Findings from The Singapore Chinese Health Study

Singapore Chinese Health Study

Eligibility criteria Singapore Chinese housing estate residents ages

45-74 years

Recruitment period April 1993 to December 1998

Cohort size Total of 63257 with 35298 women and 27959 men

Baseline data In-person interview focus on current diet-using

validated 165-item food frequency questionnaire

smoking alcohol physical activity occupational

exposures detailed menstrual and reproductive

history from women

Biospecimen Bloodbuccal cells and spot urine from consenting

subjects between 1999 and 2004 A total of 32575

subjects contributed biospecimens representing

51 of the cohort

Follow-up Disease registry death registry addressphone

updates via linkage and 2 follow-up interviews

Cigarette smoking 31 ever smokers among the 61321 subjects

Heavy smokers (12)

Started to smoke before 15 years of age AND smoked at least 13 cigarettes per day

Light smokers (88)

Started to smoke after 15 years of age OR smoked 12 or less cigarettes per day

Compared to never smokers heavy smokers were older

less educated more likely to be male had lower body

mass index (leaner) and drank more alcohol

Men (n=27292) Women (n=34028)

Never Former Current Never Former Current

Percent 422 214 364 913 25 62

Cigarettes and Lung Cancer Risk

Lung cancer

sticksday RR (95 CI)

Never 100

1-12 432 (355-523)

13-22 661 (546-802)

23+ 949 (758-1188)

P for trend lt00001

Smoking status

Lung cancer

RR (95 CI)

Never 100

Former 224 (181-278)

Current 585 (499-687)

Hazard ratios (HRs) were adjusted for age at baseline sex

dialect group and year of interview CI confidence interval

Koh et al Br J Cancer (2010)102610-4

1042 incident lung cancer cases in this cohort

after a mean follow-up of 107 years

Body Mass Index in Relation to Lung Cancer Risk by Smoking Status

Body Mass

Index (kgm2)

Never

smokers

Former

smokers

Current

smokers

Adj HR

(95 CI)

Adj HR

(95 CI)

Adj HR

(95 CI)

lt20 100 100 100

20-lt24 102 (071-146) 092 (057-148) 081 (067-099)

24-lt28 072 (046-110) 101 (059-174) 062 (046-082)

28+ 081 (046-144) 097 (044-212) 050 (028-088)

P for trend 008 089 00001


Smoking and lung cancer risk by levels of BMI

Smoking

status

lt20 kgm2 20-lt24 kgm2 24-lt28 kgm2 gt=28 kgm2

HR (95 CI) HR (95 CI) HR (95 CI) HR (95 CI)

Never 100 100 100 100

Former 246

(140-432)

197

(148-262)

296

(184-476)

199

(088-452)

Current 721

(484-1075)

520

(422-641)

550

(364-832)

321

(158-651)


Smoking and lung cancer risk by levels of BMI lt20 kgm2 20-lt24 kgm2 24-lt28 kgm2 gt=28 kgm2


Cigarettes per day (risk relative to never smokers)

1-12 618

(398-958)

365

(282-473)

365

(212-628)

290

(115-727)

13-22 792

(501-1253)

639

(498-820)

541

(323-905)

221

(071-686)

23+ 1112

(660-1870)

853

(635-1150)

901

(504-1610)

637

(210-1930)

P trend lt00001 lt00001 lt00001 00001


Biological plausibility

Body mass index influences a smokerrsquos risk

of lung cancer

Lean smokers have increased oxidative DNA

damage relative to obese smokers

Lean smokers have increased susceptibility

to tobacco carcinogens-induced DNA

damage

Public Health Implication

Rapid increase in smoking prevalence in

developing countries such as China and India

in which people still have relatively low body

weights

The adverse effect of smoking would be

stronger in the developing countries than the

developed world

Smoking and Colorectal Cancer Risk

ldquoLifestylerdquo cancer

Obesity

Western diet

Physical inactivity

Smoking

Current smoking and colorectal cancer risk Meta-analysis (18 cohort studies)

Tsoi KK et al Clin Gastroenterol Hepatol 20097682-688

Colonic carcinogens in cigarette

Polycyclic aromatic hydrocarbons (PAHs) and heterocyclic aromatic amines (HAAs)

Metabolic activation to form highly reactive mutagens that readily react with DNA bases

Undergo detoxification through conjugation reactions with the phase II enzymes to be excreted

GST enzymes

5 main classes alpha (GSTA) mu (GSTM) pi (GSTP) theta (GSTT) and zeta (GSTZ)

GSTM1 GSTT1 and GSTP1 are detoxification enzymes that have been known to metabolize a wide range of carcinogens from tobacco smoke and diet including HAAs and PAHs

High expression in the intestinal tract

These GSTs are polymorphic enzymes with inter-individual variations in enzymatic level and activity

GSTM1 and GSTT1 polymorphisms

The homozygous deletion genotypes of GSTM1 and GSTT1 result in an absence of GSTM1 and GSTT1 expression

GSTP1 polymorphism

A transition of adenine (A) to guanine (G) at nucleotide 313 in exon 5 of the GSTP1 gene results in a change from isoleucine (Ile) to valine (Val) at position 104 in the amino acid sequence of the corresponding protein

GSTP1 BB and the heterozygous variant GSTP1 AB have been shown to possess decreased specific activity and affinity for substrates

HAAs and PAHs in cigarette smoke

GSTs can deactivate HAAs and PAHs

Increased risk of Colorectal Cancer

GSTSmokingColorectal Cancer

Smokers

Hence individuals with genetically

determined decrease in GST

enzyme activity may have increased

risk of colorectal cancer risk

associated with smoking

Nested case-control study within the Singapore Chinese Health Study

480 incident colorectal cancer cases within

the cohort diagnosed as of April 30 2005

identified by linkage with nationwide cancer

registry and confirmed by verification of

histological reports or medical notes

1167 controls from a random 3 of the

cohort population and who consented to give

us blood

Cigarettes and Colorectal Cancer

Koh et al Carcinogenesis 2011 321507-11

Colorectal Colon Rectal

Smoking level OR (95 CI) OR (95 CI)

OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001

Intensity of smoking is associated with

colorectal cancer risk

GSTs and Colorectal Cancer Colorectal Colon Rectal

GSTM1 OR (95 CI) OR (95 CI) OR (95 CI)

Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)


GSTT1 OR (95 CI) OR (95 CI) OR (95 CI)

Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)


GSTP1 OR (95 CI) OR (95 CI) OR (95 CI)

AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)

No clear association between

polymorphisms of GSTM1 GSTT1 or

GSTP1 and colorectal cancer risk

No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498

GSTs and Colorectal Cancer

Null or low activity genotypes GSTM1 Null GSTT1 Null GSTP1 ABBB


No clear association between number of

genetic polymorphisms of GST enzymes

and colorectal cancer risk

GSTs Cigarettes and Colorectal Cancer



OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085



With zero GST ldquonull or low activityrdquo genotype (225)




OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052



With one GST ldquonull or low activityrdquo genotype (414)




OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003


With two or three GST ldquonull or low activityrdquo genotypes (361)

Biological Plausibility

The GSTM1GSTT1GSTP1 genotypic profile of a cigarette smoker affects hisher risk of developing colorectal cancer due to exposure from colorectal procarcinogens present in tobacco smoke

GST enzymes play important role in the detoxification of colorectal carcinogens in tobacco smoke

Wide variation in cancer incidence among smokers

A range of genetic and lifestyle factors act as determinants of a smokerrsquos risk to cancer by influencing the uptake and metabolism of tobacco carcinogens inflammatory response to the tobacco-induced lung damage and DNA repair

Gene-Environment-Smoking Interaction

Understand the mechanistic pathway of tobacco-linked carcinogenesis

Identify important pathways of activation andor deactivation of tobacco-related carcinogens

Explain heterogeneity in risk of smoking-related cancer

Identify smokers at higher risk of cancer risk

Provide strong motivation to quit smoking


Acknowledgement

Cohort Study Team

Singapore Cancer Registry

Professor Lee Hin Peng

Professor Mimi Yu

Assoc Prof Yuan Jian-Min

Dr Renwei Wang

Supported by Grants from the National Cancer Institute (NIH)

S21-1 Monitoring tobacco attributable mortality contribution to deaths for both communicable and non-communicable diseases- Edouard Tursan dEspaignet

S21-2 An updated assessment of the 4-stage model of the cigarette epidemic- Michael Thun

S21-3 Breast cancer and tobacco exposure- Kenneth C Johnson

S21-4 Lung disease in relation to tobacco exposure- Ioana Munteanu

S21-5 Genetic and Lifestyle Modifiers of Smoking on Disease Risk- Koh Woon Puay

WHO Global Report Mortality Attributable

to Tobacco

Estimates for high low and middle income countries

Effects of direct use of smoking (and smokeless) tobacco among adults aged 30+ for communicable and non-communicable diseases





Risks Mortality and

burden of disease




at WHO Regional and

country levels







999999999 + 1











40 by 2025























the PAF formula






3 broad groups




Report Layout

Report Layout

Major Findings




6 SECONDS



Findings



ndexhtml





NCD Findings





Cancer deaths 22




tobacco use




Michael Thun

Richard Peto

Jillian Boreham

Alan Lopez

WCTOH

Singapore

March 2012


of Tobacco Control

20122196-101

Original WHO Model



Value of this Model




















Methods






amp GYTS





Results




countries





in women







US

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Australia

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Netherlands

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

UK

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female





Solution


men and women


specific data


in Men

0

10

20

30

40

50

60

70

0 10 20 30 40 50 60 70 80 90 100 110 120

0

5

10

15

20

25

30

35

40

of deaths caused by

smoking



male smokers

male deaths

Sub-Saharan Africa

Southeast Asia

China Norway




in Women

0

10

20

30

40

50

60

70

0 10 20 30 40 50 60 70 80 90 100 110 120

0

5

10

15

20

25

30

35

40

of deaths caused by



female smokers

female deaths

Sub-Saharan Africa




Australia

Conclusions










Thank You







Tobacco deaths 2000

Developed 2 million




countries

Tobacco deaths 2030

3 million

7 million




0

10

20

30

40

50

60

70

0 10 20 30 40 50 60 70 80 90 100

0

5

10

15

20

25

30

35

40

of deaths caused by

smoking



19601900 1920 1940 1980 2000

male smokers

female smokers

male deaths

female deaths



through 2005



0

10

20

30

40

50

60

1965

1974

1979

1983

1985

1990

1992

1994

1995

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

2009

2010

Year

Pre

vale

nce (

)



Men

Women

(52)

(34) (215)

(173)


0

10

20

30

40

50

60

70

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Women

0

10

20

30

40

50

60

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Pre

vale

nce


Australia

Men

0

10

20

30

40

50

60

70

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Women

0

10

20

30

40

50

60

70

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Pre

vale

nce




Romania

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Greece

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Poland

0

5

10

15

20

25

30

35

40

45

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Russia

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female



United Kingdom

United States

Canada

New Zealand

Australia







Greece

Italy

Spain





Community Medicine

Faculty of Medicine


March 23 2012


Singapore

Overview




Active smoking risk

Conclusions

Passive smoking

Secondhand smoke

Involuntary smoking











Acrylamide

Acrylonitrile

13-Butadiene

Isoprene

Nitromethane

Propylene Oxide


Vinyl chloride

4-Aminobiphenyl

Urethane

Benzene

Nitrobenzene

Benzo[a]pyrene

ortho-Toluidine

Dibenzo[ae]pyrene

Dibenzo[ai]pyrene

Dibenzo[al]pyrene






Mainstream Smoke

- Carbon monoxide

- Nitrogen Oxides

- Nicotine

25-15 times as much

37-128 times

13-21 as much

- Benzene

- Formaldehyde

- NNK

- Benz(a)pyrene

- Nickel

- Tar

8-10 times as much

50 times as much

1-22 times as much

25-20 times as much

13-30 times as much

11-157 times













01

1

10H

iray

am

a 199

2W

arte

nb

erg

et

al

200

0R

eyn

old

s e

t a

l 20

04

Ha

nao

ka e

t al

200

4S

an

dle

r e

t al 1

985

Millik

an

et

al 1

998

De

lfin

o e

t al

2000

Scru

bso

le e

t al

2004

Gam

mon

et a

l 200

4S

mit

h e

t al

1994

Mo

rab

ia e

t al 1

996

Zh

ao

et

al

1999

Jo

hn

so

n e

t al

200

0K

ro

pp

et

al

200

2L

isso

wsk

a e

t al 2

00

6M

issed

Ex

po

su

re -

Co

ho

rt

Stu

die

s

Mis

sed

Ex

po

su

re -

Cas

e-C

on

tro

l

Be

tte

r E

xp

osu

re

Asses

sm

en

t



|______________________________________|



|_____________________|

Cohort

|___________________________|

Case-control






















cancerrdquo



2005 1

Surgeon Generals

Report 20062


(95 CI)

N Relative Risk

(95 CI)

All studies 19 125 (108-144) 21 120 (108-135)

Premenopausal

Women lt 50

14 168 (131-215) 11 164 (125-214)

Premenopausal

with lifetime

exposure

assessment

5 220 (169-287) 6 185 (119-287)


Balancing Concerns








Ed



0

50

100

150

200

250

USA 1994

Europe 1998

Sweden 1998

Germany 1998

China 1999

Germany 2000

China 2000

Canada 2001

Excess Lung

Cancer Risk

(Percentage)


Higher Exposure

Work Only -

Higher Exposure


+1-25

+35-220 +50-210























Teachers Cohort[48]

Adjusted HR

(95 CI)

Womenrsquos Health


Adjusted HR (95

CI)


exposure

100 100







126 (099-160) 132(104-167)





























Exposure



40+ cigday

138 (105-183)

174 (115-262)



205 (120-349)


gt20 cigday 183 (129-261)


Initiation 10-14 146 (111-193)

148 (103-213)


(premeno) 39 (15-99)


Hanaoka et al 2004



Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)






Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)

Pooled

Analysis

Never

active

100 100 100 100

lt20 105 (086-128) 123 (103-146) 091 (072-116) 110 (089-135)

gt20 149 (108-204) 142 (116-174) 129 (089-186) 088 (069-113)






initiation

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137)

Al-Delaimy(2004) 129 (097-171)

Reynolds (2004) 117 (105-130)

Lawlor (2004)

Gram (2005) 148 (103-213)

Olson (2005) 112 (092-136)

Cui (2006) 111 (097-128)

Ha (2007) 148 (077-284)

8 of 8 positive

4 of 8 Stat Sig




initiation

Longest duration

before pregnancy

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131)

Al-Delaimy(2004) 129 (097-171) 110 (080-152)

Reynolds (2004) 117 (105-130) 113 (100-125)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137)

Olson (2005) 112 (092-136) 121 (101-125)

Cui (2006) 111 (097-128) 113 (101-125)

Ha (2007) 148 (077-284) 178 (127-249)11

9 of 9 positive

4 of 9 Stat Sig




initiation

Longest duration

before pregnancy

Longest

duration

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189)

Ha (2007) 148 (077-284) 178 (127-249)11

6 of 6 positive

3 of 6 Stat Sig




initiation

Longest duration

Before pregnancy

Longest

duration

Highest pack-

years

Calle (1994) 159 (117-215) 138 (105-183)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133) 125 (106-147)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174) 146 (111-193)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138) 115 (096-137)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189) 117 (102-134)

Ha (2007) 148 (077-284) 178 (127-249)11


5 of 5 positive




First Author Year



Relative Risk

(95 CI)

Reynolds et al (2004) lt20 117 (105-130)

Olson et al (2005) lt19 112 (092-136)

Xue et al (2011) lt18 104 (099-111)

Cui et al (2006) lt16 111 (097-128)


Gram et al (2005) lt15 148 (103-213)

Ha et al (2007) lt15 148 (077-284)



















i
























bull History

bull Lung diseases


bull History

bull Lung disease



TOBACCO SMOKE








INFLAMMATION



LUNG CANCER




ndash COPD

ndash Lung cancer









times








bull History

bull Lung disease












bull History

bull Lung diseases

bull COPD









bull Findings






bull Interpretation







Follow up (y)

Po

stb

ron

cho

dila

tor

FEV

1 L

24

25

26

27

28

29

Screen 2 1 2 3 4 5

Sustained Quitters

Continuous Smokers



COPD










bull Asthma

Asthma








32 subjects


10 quit smoking

Lung cancer













200615517-523















Wen et al--2010




Kolappan Gopi--2002

Thank you




Cancer


Lung

Mouth and pharynx

Larynx

Esophagus

Stomach

Pancreas

Liver

Cervix

Bladder

Kidney

Colorectum

Breast




Body mass index






45-74 years







history from women




51 of the cohort




Heavy smokers (12)


Light smokers (88)





Men (n=27292) Women (n=34028)


Percent 422 214 364 913 25 62


Lung cancer


Never 100

1-12 432 (355-523)

13-22 661 (546-802)

23+ 949 (758-1188)

P for trend lt00001

Smoking status

Lung cancer

RR (95 CI)

Never 100

Former 224 (181-278)

Current 585 (499-687)







Body Mass

Index (kgm2)

Never

smokers

Former

smokers

Current

smokers

Adj HR

(95 CI)

Adj HR

(95 CI)

Adj HR

(95 CI)

lt20 100 100 100

20-lt24 102 (071-146) 092 (057-148) 081 (067-099)

24-lt28 072 (046-110) 101 (059-174) 062 (046-082)

28+ 081 (046-144) 097 (044-212) 050 (028-088)

P for trend 008 089 00001



Smoking

status



Never 100 100 100 100

Former 246

(140-432)

197

(148-262)

296

(184-476)

199

(088-452)

Current 721

(484-1075)

520

(422-641)

550

(364-832)

321

(158-651)





1-12 618

(398-958)

365

(282-473)

365

(212-628)

290

(115-727)

13-22 792

(501-1253)

639

(498-820)

541

(323-905)

221

(071-686)

23+ 1112

(660-1870)

853

(635-1150)

901

(504-1610)

637

(210-1930)

P trend lt00001 lt00001 lt00001 00001




of lung cancer





damage





weights



developed world



Obesity

Western diet

Physical inactivity

Smoking







GST enzymes







GSTP1 polymorphism







Smokers














us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang











Risks Mortality and

burden of disease




at WHO Regional and

country levels







999999999 + 1











40 by 2025























the PAF formula






3 broad groups




Report Layout

Report Layout

Major Findings




6 SECONDS



Findings



ndexhtml





NCD Findings





Cancer deaths 22




tobacco use




Michael Thun

Richard Peto

Jillian Boreham

Alan Lopez

WCTOH

Singapore

March 2012


of Tobacco Control

20122196-101

Original WHO Model



Value of this Model




















Methods






amp GYTS





Results




countries





in women







US

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Australia

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Netherlands

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

UK

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female





Solution


men and women


specific data


in Men

0

10

20

30

40

50

60

70

0 10 20 30 40 50 60 70 80 90 100 110 120

0

5

10

15

20

25

30

35

40

of deaths caused by

smoking



male smokers

male deaths

Sub-Saharan Africa

Southeast Asia

China Norway




in Women

0

10

20

30

40

50

60

70

0 10 20 30 40 50 60 70 80 90 100 110 120

0

5

10

15

20

25

30

35

40

of deaths caused by



female smokers

female deaths

Sub-Saharan Africa




Australia

Conclusions










Thank You







Tobacco deaths 2000

Developed 2 million




countries

Tobacco deaths 2030

3 million

7 million




0

10

20

30

40

50

60

70

0 10 20 30 40 50 60 70 80 90 100

0

5

10

15

20

25

30

35

40

of deaths caused by

smoking



19601900 1920 1940 1980 2000

male smokers

female smokers

male deaths

female deaths



through 2005



0

10

20

30

40

50

60

1965

1974

1979

1983

1985

1990

1992

1994

1995

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

2009

2010

Year

Pre

vale

nce (

)



Men

Women

(52)

(34) (215)

(173)


0

10

20

30

40

50

60

70

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Women

0

10

20

30

40

50

60

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Pre

vale

nce


Australia

Men

0

10

20

30

40

50

60

70

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Women

0

10

20

30

40

50

60

70

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Pre

vale

nce




Romania

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Greece

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Poland

0

5

10

15

20

25

30

35

40

45

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Russia

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female



United Kingdom

United States

Canada

New Zealand

Australia







Greece

Italy

Spain





Community Medicine

Faculty of Medicine


March 23 2012


Singapore

Overview




Active smoking risk

Conclusions

Passive smoking

Secondhand smoke

Involuntary smoking











Acrylamide

Acrylonitrile

13-Butadiene

Isoprene

Nitromethane

Propylene Oxide


Vinyl chloride

4-Aminobiphenyl

Urethane

Benzene

Nitrobenzene

Benzo[a]pyrene

ortho-Toluidine

Dibenzo[ae]pyrene

Dibenzo[ai]pyrene

Dibenzo[al]pyrene






Mainstream Smoke

- Carbon monoxide

- Nitrogen Oxides

- Nicotine

25-15 times as much

37-128 times

13-21 as much

- Benzene

- Formaldehyde

- NNK

- Benz(a)pyrene

- Nickel

- Tar

8-10 times as much

50 times as much

1-22 times as much

25-20 times as much

13-30 times as much

11-157 times













01

1

10H

iray

am

a 199

2W

arte

nb

erg

et

al

200

0R

eyn

old

s e

t a

l 20

04

Ha

nao

ka e

t al

200

4S

an

dle

r e

t al 1

985

Millik

an

et

al 1

998

De

lfin

o e

t al

2000

Scru

bso

le e

t al

2004

Gam

mon

et a

l 200

4S

mit

h e

t al

1994

Mo

rab

ia e

t al 1

996

Zh

ao

et

al

1999

Jo

hn

so

n e

t al

200

0K

ro

pp

et

al

200

2L

isso

wsk

a e

t al 2

00

6M

issed

Ex

po

su

re -

Co

ho

rt

Stu

die

s

Mis

sed

Ex

po

su

re -

Cas

e-C

on

tro

l

Be

tte

r E

xp

osu

re

Asses

sm

en

t



|______________________________________|



|_____________________|

Cohort

|___________________________|

Case-control






















cancerrdquo



2005 1

Surgeon Generals

Report 20062


(95 CI)

N Relative Risk

(95 CI)

All studies 19 125 (108-144) 21 120 (108-135)

Premenopausal

Women lt 50

14 168 (131-215) 11 164 (125-214)

Premenopausal

with lifetime

exposure

assessment

5 220 (169-287) 6 185 (119-287)


Balancing Concerns








Ed



0

50

100

150

200

250

USA 1994

Europe 1998

Sweden 1998

Germany 1998

China 1999

Germany 2000

China 2000

Canada 2001

Excess Lung

Cancer Risk

(Percentage)


Higher Exposure

Work Only -

Higher Exposure


+1-25

+35-220 +50-210























Teachers Cohort[48]

Adjusted HR

(95 CI)

Womenrsquos Health


Adjusted HR (95

CI)


exposure

100 100







126 (099-160) 132(104-167)





























Exposure



40+ cigday

138 (105-183)

174 (115-262)



205 (120-349)


gt20 cigday 183 (129-261)


Initiation 10-14 146 (111-193)

148 (103-213)


(premeno) 39 (15-99)


Hanaoka et al 2004



Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)






Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)

Pooled

Analysis

Never

active

100 100 100 100

lt20 105 (086-128) 123 (103-146) 091 (072-116) 110 (089-135)

gt20 149 (108-204) 142 (116-174) 129 (089-186) 088 (069-113)






initiation

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137)

Al-Delaimy(2004) 129 (097-171)

Reynolds (2004) 117 (105-130)

Lawlor (2004)

Gram (2005) 148 (103-213)

Olson (2005) 112 (092-136)

Cui (2006) 111 (097-128)

Ha (2007) 148 (077-284)

8 of 8 positive

4 of 8 Stat Sig




initiation

Longest duration

before pregnancy

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131)

Al-Delaimy(2004) 129 (097-171) 110 (080-152)

Reynolds (2004) 117 (105-130) 113 (100-125)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137)

Olson (2005) 112 (092-136) 121 (101-125)

Cui (2006) 111 (097-128) 113 (101-125)

Ha (2007) 148 (077-284) 178 (127-249)11

9 of 9 positive

4 of 9 Stat Sig




initiation

Longest duration

before pregnancy

Longest

duration

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189)

Ha (2007) 148 (077-284) 178 (127-249)11

6 of 6 positive

3 of 6 Stat Sig




initiation

Longest duration

Before pregnancy

Longest

duration

Highest pack-

years

Calle (1994) 159 (117-215) 138 (105-183)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133) 125 (106-147)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174) 146 (111-193)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138) 115 (096-137)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189) 117 (102-134)

Ha (2007) 148 (077-284) 178 (127-249)11


5 of 5 positive




First Author Year



Relative Risk

(95 CI)

Reynolds et al (2004) lt20 117 (105-130)

Olson et al (2005) lt19 112 (092-136)

Xue et al (2011) lt18 104 (099-111)

Cui et al (2006) lt16 111 (097-128)


Gram et al (2005) lt15 148 (103-213)

Ha et al (2007) lt15 148 (077-284)



















i
























bull History

bull Lung diseases


bull History

bull Lung disease



TOBACCO SMOKE








INFLAMMATION



LUNG CANCER




ndash COPD

ndash Lung cancer









times








bull History

bull Lung disease












bull History

bull Lung diseases

bull COPD









bull Findings






bull Interpretation







Follow up (y)

Po

stb

ron

cho

dila

tor

FEV

1 L

24

25

26

27

28

29

Screen 2 1 2 3 4 5

Sustained Quitters

Continuous Smokers



COPD










bull Asthma

Asthma








32 subjects


10 quit smoking

Lung cancer













200615517-523















Wen et al--2010




Kolappan Gopi--2002

Thank you




Cancer


Lung

Mouth and pharynx

Larynx

Esophagus

Stomach

Pancreas

Liver

Cervix

Bladder

Kidney

Colorectum

Breast




Body mass index






45-74 years







history from women




51 of the cohort




Heavy smokers (12)


Light smokers (88)





Men (n=27292) Women (n=34028)


Percent 422 214 364 913 25 62


Lung cancer


Never 100

1-12 432 (355-523)

13-22 661 (546-802)

23+ 949 (758-1188)

P for trend lt00001

Smoking status

Lung cancer

RR (95 CI)

Never 100

Former 224 (181-278)

Current 585 (499-687)







Body Mass

Index (kgm2)

Never

smokers

Former

smokers

Current

smokers

Adj HR

(95 CI)

Adj HR

(95 CI)

Adj HR

(95 CI)

lt20 100 100 100

20-lt24 102 (071-146) 092 (057-148) 081 (067-099)

24-lt28 072 (046-110) 101 (059-174) 062 (046-082)

28+ 081 (046-144) 097 (044-212) 050 (028-088)

P for trend 008 089 00001



Smoking

status



Never 100 100 100 100

Former 246

(140-432)

197

(148-262)

296

(184-476)

199

(088-452)

Current 721

(484-1075)

520

(422-641)

550

(364-832)

321

(158-651)





1-12 618

(398-958)

365

(282-473)

365

(212-628)

290

(115-727)

13-22 792

(501-1253)

639

(498-820)

541

(323-905)

221

(071-686)

23+ 1112

(660-1870)

853

(635-1150)

901

(504-1610)

637

(210-1930)

P trend lt00001 lt00001 lt00001 00001




of lung cancer





damage





weights



developed world



Obesity

Western diet

Physical inactivity

Smoking







GST enzymes







GSTP1 polymorphism







Smokers














us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang













999999999 + 1











40 by 2025























the PAF formula






3 broad groups




Report Layout

Report Layout

Major Findings




6 SECONDS



Findings



ndexhtml





NCD Findings





Cancer deaths 22




tobacco use




Michael Thun

Richard Peto

Jillian Boreham

Alan Lopez

WCTOH

Singapore

March 2012


of Tobacco Control

20122196-101

Original WHO Model



Value of this Model




















Methods






amp GYTS





Results




countries





in women







US

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Australia

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Netherlands

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

UK

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female





Solution


men and women


specific data


in Men

0

10

20

30

40

50

60

70

0 10 20 30 40 50 60 70 80 90 100 110 120

0

5

10

15

20

25

30

35

40

of deaths caused by

smoking



male smokers

male deaths

Sub-Saharan Africa

Southeast Asia

China Norway




in Women

0

10

20

30

40

50

60

70

0 10 20 30 40 50 60 70 80 90 100 110 120

0

5

10

15

20

25

30

35

40

of deaths caused by



female smokers

female deaths

Sub-Saharan Africa




Australia

Conclusions










Thank You







Tobacco deaths 2000

Developed 2 million




countries

Tobacco deaths 2030

3 million

7 million




0

10

20

30

40

50

60

70

0 10 20 30 40 50 60 70 80 90 100

0

5

10

15

20

25

30

35

40

of deaths caused by

smoking



19601900 1920 1940 1980 2000

male smokers

female smokers

male deaths

female deaths



through 2005



0

10

20

30

40

50

60

1965

1974

1979

1983

1985

1990

1992

1994

1995

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

2009

2010

Year

Pre

vale

nce (

)



Men

Women

(52)

(34) (215)

(173)


0

10

20

30

40

50

60

70

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Women

0

10

20

30

40

50

60

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Pre

vale

nce


Australia

Men

0

10

20

30

40

50

60

70

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Women

0

10

20

30

40

50

60

70

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Pre

vale

nce




Romania

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Greece

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Poland

0

5

10

15

20

25

30

35

40

45

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Russia

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female



United Kingdom

United States

Canada

New Zealand

Australia







Greece

Italy

Spain





Community Medicine

Faculty of Medicine


March 23 2012


Singapore

Overview




Active smoking risk

Conclusions

Passive smoking

Secondhand smoke

Involuntary smoking











Acrylamide

Acrylonitrile

13-Butadiene

Isoprene

Nitromethane

Propylene Oxide


Vinyl chloride

4-Aminobiphenyl

Urethane

Benzene

Nitrobenzene

Benzo[a]pyrene

ortho-Toluidine

Dibenzo[ae]pyrene

Dibenzo[ai]pyrene

Dibenzo[al]pyrene






Mainstream Smoke

- Carbon monoxide

- Nitrogen Oxides

- Nicotine

25-15 times as much

37-128 times

13-21 as much

- Benzene

- Formaldehyde

- NNK

- Benz(a)pyrene

- Nickel

- Tar

8-10 times as much

50 times as much

1-22 times as much

25-20 times as much

13-30 times as much

11-157 times













01

1

10H

iray

am

a 199

2W

arte

nb

erg

et

al

200

0R

eyn

old

s e

t a

l 20

04

Ha

nao

ka e

t al

200

4S

an

dle

r e

t al 1

985

Millik

an

et

al 1

998

De

lfin

o e

t al

2000

Scru

bso

le e

t al

2004

Gam

mon

et a

l 200

4S

mit

h e

t al

1994

Mo

rab

ia e

t al 1

996

Zh

ao

et

al

1999

Jo

hn

so

n e

t al

200

0K

ro

pp

et

al

200

2L

isso

wsk

a e

t al 2

00

6M

issed

Ex

po

su

re -

Co

ho

rt

Stu

die

s

Mis

sed

Ex

po

su

re -

Cas

e-C

on

tro

l

Be

tte

r E

xp

osu

re

Asses

sm

en

t



|______________________________________|



|_____________________|

Cohort

|___________________________|

Case-control






















cancerrdquo



2005 1

Surgeon Generals

Report 20062


(95 CI)

N Relative Risk

(95 CI)

All studies 19 125 (108-144) 21 120 (108-135)

Premenopausal

Women lt 50

14 168 (131-215) 11 164 (125-214)

Premenopausal

with lifetime

exposure

assessment

5 220 (169-287) 6 185 (119-287)


Balancing Concerns








Ed



0

50

100

150

200

250

USA 1994

Europe 1998

Sweden 1998

Germany 1998

China 1999

Germany 2000

China 2000

Canada 2001

Excess Lung

Cancer Risk

(Percentage)


Higher Exposure

Work Only -

Higher Exposure


+1-25

+35-220 +50-210























Teachers Cohort[48]

Adjusted HR

(95 CI)

Womenrsquos Health


Adjusted HR (95

CI)


exposure

100 100







126 (099-160) 132(104-167)





























Exposure



40+ cigday

138 (105-183)

174 (115-262)



205 (120-349)


gt20 cigday 183 (129-261)


Initiation 10-14 146 (111-193)

148 (103-213)


(premeno) 39 (15-99)


Hanaoka et al 2004



Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)






Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)

Pooled

Analysis

Never

active

100 100 100 100

lt20 105 (086-128) 123 (103-146) 091 (072-116) 110 (089-135)

gt20 149 (108-204) 142 (116-174) 129 (089-186) 088 (069-113)






initiation

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137)

Al-Delaimy(2004) 129 (097-171)

Reynolds (2004) 117 (105-130)

Lawlor (2004)

Gram (2005) 148 (103-213)

Olson (2005) 112 (092-136)

Cui (2006) 111 (097-128)

Ha (2007) 148 (077-284)

8 of 8 positive

4 of 8 Stat Sig




initiation

Longest duration

before pregnancy

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131)

Al-Delaimy(2004) 129 (097-171) 110 (080-152)

Reynolds (2004) 117 (105-130) 113 (100-125)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137)

Olson (2005) 112 (092-136) 121 (101-125)

Cui (2006) 111 (097-128) 113 (101-125)

Ha (2007) 148 (077-284) 178 (127-249)11

9 of 9 positive

4 of 9 Stat Sig




initiation

Longest duration

before pregnancy

Longest

duration

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189)

Ha (2007) 148 (077-284) 178 (127-249)11

6 of 6 positive

3 of 6 Stat Sig




initiation

Longest duration

Before pregnancy

Longest

duration

Highest pack-

years

Calle (1994) 159 (117-215) 138 (105-183)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133) 125 (106-147)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174) 146 (111-193)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138) 115 (096-137)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189) 117 (102-134)

Ha (2007) 148 (077-284) 178 (127-249)11


5 of 5 positive




First Author Year



Relative Risk

(95 CI)

Reynolds et al (2004) lt20 117 (105-130)

Olson et al (2005) lt19 112 (092-136)

Xue et al (2011) lt18 104 (099-111)

Cui et al (2006) lt16 111 (097-128)


Gram et al (2005) lt15 148 (103-213)

Ha et al (2007) lt15 148 (077-284)



















i
























bull History

bull Lung diseases


bull History

bull Lung disease



TOBACCO SMOKE








INFLAMMATION



LUNG CANCER




ndash COPD

ndash Lung cancer









times








bull History

bull Lung disease












bull History

bull Lung diseases

bull COPD









bull Findings






bull Interpretation







Follow up (y)

Po

stb

ron

cho

dila

tor

FEV

1 L

24

25

26

27

28

29

Screen 2 1 2 3 4 5

Sustained Quitters

Continuous Smokers



COPD










bull Asthma

Asthma








32 subjects


10 quit smoking

Lung cancer













200615517-523















Wen et al--2010




Kolappan Gopi--2002

Thank you




Cancer


Lung

Mouth and pharynx

Larynx

Esophagus

Stomach

Pancreas

Liver

Cervix

Bladder

Kidney

Colorectum

Breast




Body mass index






45-74 years







history from women




51 of the cohort




Heavy smokers (12)


Light smokers (88)





Men (n=27292) Women (n=34028)


Percent 422 214 364 913 25 62


Lung cancer


Never 100

1-12 432 (355-523)

13-22 661 (546-802)

23+ 949 (758-1188)

P for trend lt00001

Smoking status

Lung cancer

RR (95 CI)

Never 100

Former 224 (181-278)

Current 585 (499-687)







Body Mass

Index (kgm2)

Never

smokers

Former

smokers

Current

smokers

Adj HR

(95 CI)

Adj HR

(95 CI)

Adj HR

(95 CI)

lt20 100 100 100

20-lt24 102 (071-146) 092 (057-148) 081 (067-099)

24-lt28 072 (046-110) 101 (059-174) 062 (046-082)

28+ 081 (046-144) 097 (044-212) 050 (028-088)

P for trend 008 089 00001



Smoking

status



Never 100 100 100 100

Former 246

(140-432)

197

(148-262)

296

(184-476)

199

(088-452)

Current 721

(484-1075)

520

(422-641)

550

(364-832)

321

(158-651)





1-12 618

(398-958)

365

(282-473)

365

(212-628)

290

(115-727)

13-22 792

(501-1253)

639

(498-820)

541

(323-905)

221

(071-686)

23+ 1112

(660-1870)

853

(635-1150)

901

(504-1610)

637

(210-1930)

P trend lt00001 lt00001 lt00001 00001




of lung cancer





damage





weights



developed world



Obesity

Western diet

Physical inactivity

Smoking







GST enzymes







GSTP1 polymorphism







Smokers














us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang

















40 by 2025























the PAF formula






3 broad groups




Report Layout

Report Layout

Major Findings




6 SECONDS



Findings



ndexhtml





NCD Findings





Cancer deaths 22




tobacco use




Michael Thun

Richard Peto

Jillian Boreham

Alan Lopez

WCTOH

Singapore

March 2012


of Tobacco Control

20122196-101

Original WHO Model



Value of this Model




















Methods






amp GYTS





Results




countries





in women







US

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Australia

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Netherlands

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

UK

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female





Solution


men and women


specific data


in Men

0

10

20

30

40

50

60

70

0 10 20 30 40 50 60 70 80 90 100 110 120

0

5

10

15

20

25

30

35

40

of deaths caused by

smoking



male smokers

male deaths

Sub-Saharan Africa

Southeast Asia

China Norway




in Women

0

10

20

30

40

50

60

70

0 10 20 30 40 50 60 70 80 90 100 110 120

0

5

10

15

20

25

30

35

40

of deaths caused by



female smokers

female deaths

Sub-Saharan Africa




Australia

Conclusions










Thank You







Tobacco deaths 2000

Developed 2 million




countries

Tobacco deaths 2030

3 million

7 million




0

10

20

30

40

50

60

70

0 10 20 30 40 50 60 70 80 90 100

0

5

10

15

20

25

30

35

40

of deaths caused by

smoking



19601900 1920 1940 1980 2000

male smokers

female smokers

male deaths

female deaths



through 2005



0

10

20

30

40

50

60

1965

1974

1979

1983

1985

1990

1992

1994

1995

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

2009

2010

Year

Pre

vale

nce (

)



Men

Women

(52)

(34) (215)

(173)


0

10

20

30

40

50

60

70

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Women

0

10

20

30

40

50

60

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Pre

vale

nce


Australia

Men

0

10

20

30

40

50

60

70

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Women

0

10

20

30

40

50

60

70

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Pre

vale

nce




Romania

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Greece

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Poland

0

5

10

15

20

25

30

35

40

45

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Russia

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female



United Kingdom

United States

Canada

New Zealand

Australia







Greece

Italy

Spain





Community Medicine

Faculty of Medicine


March 23 2012


Singapore

Overview




Active smoking risk

Conclusions

Passive smoking

Secondhand smoke

Involuntary smoking











Acrylamide

Acrylonitrile

13-Butadiene

Isoprene

Nitromethane

Propylene Oxide


Vinyl chloride

4-Aminobiphenyl

Urethane

Benzene

Nitrobenzene

Benzo[a]pyrene

ortho-Toluidine

Dibenzo[ae]pyrene

Dibenzo[ai]pyrene

Dibenzo[al]pyrene






Mainstream Smoke

- Carbon monoxide

- Nitrogen Oxides

- Nicotine

25-15 times as much

37-128 times

13-21 as much

- Benzene

- Formaldehyde

- NNK

- Benz(a)pyrene

- Nickel

- Tar

8-10 times as much

50 times as much

1-22 times as much

25-20 times as much

13-30 times as much

11-157 times













01

1

10H

iray

am

a 199

2W

arte

nb

erg

et

al

200

0R

eyn

old

s e

t a

l 20

04

Ha

nao

ka e

t al

200

4S

an

dle

r e

t al 1

985

Millik

an

et

al 1

998

De

lfin

o e

t al

2000

Scru

bso

le e

t al

2004

Gam

mon

et a

l 200

4S

mit

h e

t al

1994

Mo

rab

ia e

t al 1

996

Zh

ao

et

al

1999

Jo

hn

so

n e

t al

200

0K

ro

pp

et

al

200

2L

isso

wsk

a e

t al 2

00

6M

issed

Ex

po

su

re -

Co

ho

rt

Stu

die

s

Mis

sed

Ex

po

su

re -

Cas

e-C

on

tro

l

Be

tte

r E

xp

osu

re

Asses

sm

en

t



|______________________________________|



|_____________________|

Cohort

|___________________________|

Case-control






















cancerrdquo



2005 1

Surgeon Generals

Report 20062


(95 CI)

N Relative Risk

(95 CI)

All studies 19 125 (108-144) 21 120 (108-135)

Premenopausal

Women lt 50

14 168 (131-215) 11 164 (125-214)

Premenopausal

with lifetime

exposure

assessment

5 220 (169-287) 6 185 (119-287)


Balancing Concerns








Ed



0

50

100

150

200

250

USA 1994

Europe 1998

Sweden 1998

Germany 1998

China 1999

Germany 2000

China 2000

Canada 2001

Excess Lung

Cancer Risk

(Percentage)


Higher Exposure

Work Only -

Higher Exposure


+1-25

+35-220 +50-210























Teachers Cohort[48]

Adjusted HR

(95 CI)

Womenrsquos Health


Adjusted HR (95

CI)


exposure

100 100







126 (099-160) 132(104-167)





























Exposure



40+ cigday

138 (105-183)

174 (115-262)



205 (120-349)


gt20 cigday 183 (129-261)


Initiation 10-14 146 (111-193)

148 (103-213)


(premeno) 39 (15-99)


Hanaoka et al 2004



Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)






Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)

Pooled

Analysis

Never

active

100 100 100 100

lt20 105 (086-128) 123 (103-146) 091 (072-116) 110 (089-135)

gt20 149 (108-204) 142 (116-174) 129 (089-186) 088 (069-113)






initiation

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137)

Al-Delaimy(2004) 129 (097-171)

Reynolds (2004) 117 (105-130)

Lawlor (2004)

Gram (2005) 148 (103-213)

Olson (2005) 112 (092-136)

Cui (2006) 111 (097-128)

Ha (2007) 148 (077-284)

8 of 8 positive

4 of 8 Stat Sig




initiation

Longest duration

before pregnancy

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131)

Al-Delaimy(2004) 129 (097-171) 110 (080-152)

Reynolds (2004) 117 (105-130) 113 (100-125)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137)

Olson (2005) 112 (092-136) 121 (101-125)

Cui (2006) 111 (097-128) 113 (101-125)

Ha (2007) 148 (077-284) 178 (127-249)11

9 of 9 positive

4 of 9 Stat Sig




initiation

Longest duration

before pregnancy

Longest

duration

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189)

Ha (2007) 148 (077-284) 178 (127-249)11

6 of 6 positive

3 of 6 Stat Sig




initiation

Longest duration

Before pregnancy

Longest

duration

Highest pack-

years

Calle (1994) 159 (117-215) 138 (105-183)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133) 125 (106-147)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174) 146 (111-193)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138) 115 (096-137)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189) 117 (102-134)

Ha (2007) 148 (077-284) 178 (127-249)11


5 of 5 positive




First Author Year



Relative Risk

(95 CI)

Reynolds et al (2004) lt20 117 (105-130)

Olson et al (2005) lt19 112 (092-136)

Xue et al (2011) lt18 104 (099-111)

Cui et al (2006) lt16 111 (097-128)


Gram et al (2005) lt15 148 (103-213)

Ha et al (2007) lt15 148 (077-284)



















i
























bull History

bull Lung diseases


bull History

bull Lung disease



TOBACCO SMOKE








INFLAMMATION



LUNG CANCER




ndash COPD

ndash Lung cancer









times








bull History

bull Lung disease












bull History

bull Lung diseases

bull COPD









bull Findings






bull Interpretation







Follow up (y)

Po

stb

ron

cho

dila

tor

FEV

1 L

24

25

26

27

28

29

Screen 2 1 2 3 4 5

Sustained Quitters

Continuous Smokers



COPD










bull Asthma

Asthma








32 subjects


10 quit smoking

Lung cancer













200615517-523















Wen et al--2010




Kolappan Gopi--2002

Thank you




Cancer


Lung

Mouth and pharynx

Larynx

Esophagus

Stomach

Pancreas

Liver

Cervix

Bladder

Kidney

Colorectum

Breast




Body mass index






45-74 years







history from women




51 of the cohort




Heavy smokers (12)


Light smokers (88)





Men (n=27292) Women (n=34028)


Percent 422 214 364 913 25 62


Lung cancer


Never 100

1-12 432 (355-523)

13-22 661 (546-802)

23+ 949 (758-1188)

P for trend lt00001

Smoking status

Lung cancer

RR (95 CI)

Never 100

Former 224 (181-278)

Current 585 (499-687)







Body Mass

Index (kgm2)

Never

smokers

Former

smokers

Current

smokers

Adj HR

(95 CI)

Adj HR

(95 CI)

Adj HR

(95 CI)

lt20 100 100 100

20-lt24 102 (071-146) 092 (057-148) 081 (067-099)

24-lt28 072 (046-110) 101 (059-174) 062 (046-082)

28+ 081 (046-144) 097 (044-212) 050 (028-088)

P for trend 008 089 00001



Smoking

status



Never 100 100 100 100

Former 246

(140-432)

197

(148-262)

296

(184-476)

199

(088-452)

Current 721

(484-1075)

520

(422-641)

550

(364-832)

321

(158-651)





1-12 618

(398-958)

365

(282-473)

365

(212-628)

290

(115-727)

13-22 792

(501-1253)

639

(498-820)

541

(323-905)

221

(071-686)

23+ 1112

(660-1870)

853

(635-1150)

901

(504-1610)

637

(210-1930)

P trend lt00001 lt00001 lt00001 00001




of lung cancer





damage





weights



developed world



Obesity

Western diet

Physical inactivity

Smoking







GST enzymes







GSTP1 polymorphism







Smokers














us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang


























the PAF formula






3 broad groups




Report Layout

Report Layout

Major Findings




6 SECONDS



Findings



ndexhtml





NCD Findings





Cancer deaths 22




tobacco use




Michael Thun

Richard Peto

Jillian Boreham

Alan Lopez

WCTOH

Singapore

March 2012


of Tobacco Control

20122196-101

Original WHO Model



Value of this Model




















Methods






amp GYTS





Results




countries





in women







US

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Australia

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Netherlands

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

UK

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female





Solution


men and women


specific data


in Men

0

10

20

30

40

50

60

70

0 10 20 30 40 50 60 70 80 90 100 110 120

0

5

10

15

20

25

30

35

40

of deaths caused by

smoking



male smokers

male deaths

Sub-Saharan Africa

Southeast Asia

China Norway




in Women

0

10

20

30

40

50

60

70

0 10 20 30 40 50 60 70 80 90 100 110 120

0

5

10

15

20

25

30

35

40

of deaths caused by



female smokers

female deaths

Sub-Saharan Africa




Australia

Conclusions










Thank You







Tobacco deaths 2000

Developed 2 million




countries

Tobacco deaths 2030

3 million

7 million




0

10

20

30

40

50

60

70

0 10 20 30 40 50 60 70 80 90 100

0

5

10

15

20

25

30

35

40

of deaths caused by

smoking



19601900 1920 1940 1980 2000

male smokers

female smokers

male deaths

female deaths



through 2005



0

10

20

30

40

50

60

1965

1974

1979

1983

1985

1990

1992

1994

1995

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

2009

2010

Year

Pre

vale

nce (

)



Men

Women

(52)

(34) (215)

(173)


0

10

20

30

40

50

60

70

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Women

0

10

20

30

40

50

60

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Pre

vale

nce


Australia

Men

0

10

20

30

40

50

60

70

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Women

0

10

20

30

40

50

60

70

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Pre

vale

nce




Romania

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Greece

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Poland

0

5

10

15

20

25

30

35

40

45

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Russia

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female



United Kingdom

United States

Canada

New Zealand

Australia







Greece

Italy

Spain





Community Medicine

Faculty of Medicine


March 23 2012


Singapore

Overview




Active smoking risk

Conclusions

Passive smoking

Secondhand smoke

Involuntary smoking











Acrylamide

Acrylonitrile

13-Butadiene

Isoprene

Nitromethane

Propylene Oxide


Vinyl chloride

4-Aminobiphenyl

Urethane

Benzene

Nitrobenzene

Benzo[a]pyrene

ortho-Toluidine

Dibenzo[ae]pyrene

Dibenzo[ai]pyrene

Dibenzo[al]pyrene






Mainstream Smoke

- Carbon monoxide

- Nitrogen Oxides

- Nicotine

25-15 times as much

37-128 times

13-21 as much

- Benzene

- Formaldehyde

- NNK

- Benz(a)pyrene

- Nickel

- Tar

8-10 times as much

50 times as much

1-22 times as much

25-20 times as much

13-30 times as much

11-157 times













01

1

10H

iray

am

a 199

2W

arte

nb

erg

et

al

200

0R

eyn

old

s e

t a

l 20

04

Ha

nao

ka e

t al

200

4S

an

dle

r e

t al 1

985

Millik

an

et

al 1

998

De

lfin

o e

t al

2000

Scru

bso

le e

t al

2004

Gam

mon

et a

l 200

4S

mit

h e

t al

1994

Mo

rab

ia e

t al 1

996

Zh

ao

et

al

1999

Jo

hn

so

n e

t al

200

0K

ro

pp

et

al

200

2L

isso

wsk

a e

t al 2

00

6M

issed

Ex

po

su

re -

Co

ho

rt

Stu

die

s

Mis

sed

Ex

po

su

re -

Cas

e-C

on

tro

l

Be

tte

r E

xp

osu

re

Asses

sm

en

t



|______________________________________|



|_____________________|

Cohort

|___________________________|

Case-control






















cancerrdquo



2005 1

Surgeon Generals

Report 20062


(95 CI)

N Relative Risk

(95 CI)

All studies 19 125 (108-144) 21 120 (108-135)

Premenopausal

Women lt 50

14 168 (131-215) 11 164 (125-214)

Premenopausal

with lifetime

exposure

assessment

5 220 (169-287) 6 185 (119-287)


Balancing Concerns








Ed



0

50

100

150

200

250

USA 1994

Europe 1998

Sweden 1998

Germany 1998

China 1999

Germany 2000

China 2000

Canada 2001

Excess Lung

Cancer Risk

(Percentage)


Higher Exposure

Work Only -

Higher Exposure


+1-25

+35-220 +50-210























Teachers Cohort[48]

Adjusted HR

(95 CI)

Womenrsquos Health


Adjusted HR (95

CI)


exposure

100 100







126 (099-160) 132(104-167)





























Exposure



40+ cigday

138 (105-183)

174 (115-262)



205 (120-349)


gt20 cigday 183 (129-261)


Initiation 10-14 146 (111-193)

148 (103-213)


(premeno) 39 (15-99)


Hanaoka et al 2004



Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)






Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)

Pooled

Analysis

Never

active

100 100 100 100

lt20 105 (086-128) 123 (103-146) 091 (072-116) 110 (089-135)

gt20 149 (108-204) 142 (116-174) 129 (089-186) 088 (069-113)






initiation

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137)

Al-Delaimy(2004) 129 (097-171)

Reynolds (2004) 117 (105-130)

Lawlor (2004)

Gram (2005) 148 (103-213)

Olson (2005) 112 (092-136)

Cui (2006) 111 (097-128)

Ha (2007) 148 (077-284)

8 of 8 positive

4 of 8 Stat Sig




initiation

Longest duration

before pregnancy

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131)

Al-Delaimy(2004) 129 (097-171) 110 (080-152)

Reynolds (2004) 117 (105-130) 113 (100-125)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137)

Olson (2005) 112 (092-136) 121 (101-125)

Cui (2006) 111 (097-128) 113 (101-125)

Ha (2007) 148 (077-284) 178 (127-249)11

9 of 9 positive

4 of 9 Stat Sig




initiation

Longest duration

before pregnancy

Longest

duration

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189)

Ha (2007) 148 (077-284) 178 (127-249)11

6 of 6 positive

3 of 6 Stat Sig




initiation

Longest duration

Before pregnancy

Longest

duration

Highest pack-

years

Calle (1994) 159 (117-215) 138 (105-183)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133) 125 (106-147)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174) 146 (111-193)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138) 115 (096-137)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189) 117 (102-134)

Ha (2007) 148 (077-284) 178 (127-249)11


5 of 5 positive




First Author Year



Relative Risk

(95 CI)

Reynolds et al (2004) lt20 117 (105-130)

Olson et al (2005) lt19 112 (092-136)

Xue et al (2011) lt18 104 (099-111)

Cui et al (2006) lt16 111 (097-128)


Gram et al (2005) lt15 148 (103-213)

Ha et al (2007) lt15 148 (077-284)



















i
























bull History

bull Lung diseases


bull History

bull Lung disease



TOBACCO SMOKE








INFLAMMATION



LUNG CANCER




ndash COPD

ndash Lung cancer









times








bull History

bull Lung disease












bull History

bull Lung diseases

bull COPD









bull Findings






bull Interpretation







Follow up (y)

Po

stb

ron

cho

dila

tor

FEV

1 L

24

25

26

27

28

29

Screen 2 1 2 3 4 5

Sustained Quitters

Continuous Smokers



COPD










bull Asthma

Asthma








32 subjects


10 quit smoking

Lung cancer













200615517-523















Wen et al--2010




Kolappan Gopi--2002

Thank you




Cancer


Lung

Mouth and pharynx

Larynx

Esophagus

Stomach

Pancreas

Liver

Cervix

Bladder

Kidney

Colorectum

Breast




Body mass index






45-74 years







history from women




51 of the cohort




Heavy smokers (12)


Light smokers (88)





Men (n=27292) Women (n=34028)


Percent 422 214 364 913 25 62


Lung cancer


Never 100

1-12 432 (355-523)

13-22 661 (546-802)

23+ 949 (758-1188)

P for trend lt00001

Smoking status

Lung cancer

RR (95 CI)

Never 100

Former 224 (181-278)

Current 585 (499-687)







Body Mass

Index (kgm2)

Never

smokers

Former

smokers

Current

smokers

Adj HR

(95 CI)

Adj HR

(95 CI)

Adj HR

(95 CI)

lt20 100 100 100

20-lt24 102 (071-146) 092 (057-148) 081 (067-099)

24-lt28 072 (046-110) 101 (059-174) 062 (046-082)

28+ 081 (046-144) 097 (044-212) 050 (028-088)

P for trend 008 089 00001



Smoking

status



Never 100 100 100 100

Former 246

(140-432)

197

(148-262)

296

(184-476)

199

(088-452)

Current 721

(484-1075)

520

(422-641)

550

(364-832)

321

(158-651)





1-12 618

(398-958)

365

(282-473)

365

(212-628)

290

(115-727)

13-22 792

(501-1253)

639

(498-820)

541

(323-905)

221

(071-686)

23+ 1112

(660-1870)

853

(635-1150)

901

(504-1610)

637

(210-1930)

P trend lt00001 lt00001 lt00001 00001




of lung cancer





damage





weights



developed world



Obesity

Western diet

Physical inactivity

Smoking







GST enzymes







GSTP1 polymorphism







Smokers














us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang








3 broad groups




Report Layout

Report Layout

Major Findings




6 SECONDS



Findings



ndexhtml





NCD Findings





Cancer deaths 22




tobacco use




Michael Thun

Richard Peto

Jillian Boreham

Alan Lopez

WCTOH

Singapore

March 2012


of Tobacco Control

20122196-101

Original WHO Model



Value of this Model




















Methods






amp GYTS





Results




countries





in women







US

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Australia

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Netherlands

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

UK

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female





Solution


men and women


specific data


in Men

0

10

20

30

40

50

60

70

0 10 20 30 40 50 60 70 80 90 100 110 120

0

5

10

15

20

25

30

35

40

of deaths caused by

smoking



male smokers

male deaths

Sub-Saharan Africa

Southeast Asia

China Norway




in Women

0

10

20

30

40

50

60

70

0 10 20 30 40 50 60 70 80 90 100 110 120

0

5

10

15

20

25

30

35

40

of deaths caused by



female smokers

female deaths

Sub-Saharan Africa




Australia

Conclusions










Thank You







Tobacco deaths 2000

Developed 2 million




countries

Tobacco deaths 2030

3 million

7 million




0

10

20

30

40

50

60

70

0 10 20 30 40 50 60 70 80 90 100

0

5

10

15

20

25

30

35

40

of deaths caused by

smoking



19601900 1920 1940 1980 2000

male smokers

female smokers

male deaths

female deaths



through 2005



0

10

20

30

40

50

60

1965

1974

1979

1983

1985

1990

1992

1994

1995

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

2009

2010

Year

Pre

vale

nce (

)



Men

Women

(52)

(34) (215)

(173)


0

10

20

30

40

50

60

70

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Women

0

10

20

30

40

50

60

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Pre

vale

nce


Australia

Men

0

10

20

30

40

50

60

70

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Women

0

10

20

30

40

50

60

70

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Pre

vale

nce




Romania

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Greece

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Poland

0

5

10

15

20

25

30

35

40

45

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Russia

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female



United Kingdom

United States

Canada

New Zealand

Australia







Greece

Italy

Spain





Community Medicine

Faculty of Medicine


March 23 2012


Singapore

Overview




Active smoking risk

Conclusions

Passive smoking

Secondhand smoke

Involuntary smoking











Acrylamide

Acrylonitrile

13-Butadiene

Isoprene

Nitromethane

Propylene Oxide


Vinyl chloride

4-Aminobiphenyl

Urethane

Benzene

Nitrobenzene

Benzo[a]pyrene

ortho-Toluidine

Dibenzo[ae]pyrene

Dibenzo[ai]pyrene

Dibenzo[al]pyrene






Mainstream Smoke

- Carbon monoxide

- Nitrogen Oxides

- Nicotine

25-15 times as much

37-128 times

13-21 as much

- Benzene

- Formaldehyde

- NNK

- Benz(a)pyrene

- Nickel

- Tar

8-10 times as much

50 times as much

1-22 times as much

25-20 times as much

13-30 times as much

11-157 times













01

1

10H

iray

am

a 199

2W

arte

nb

erg

et

al

200

0R

eyn

old

s e

t a

l 20

04

Ha

nao

ka e

t al

200

4S

an

dle

r e

t al 1

985

Millik

an

et

al 1

998

De

lfin

o e

t al

2000

Scru

bso

le e

t al

2004

Gam

mon

et a

l 200

4S

mit

h e

t al

1994

Mo

rab

ia e

t al 1

996

Zh

ao

et

al

1999

Jo

hn

so

n e

t al

200

0K

ro

pp

et

al

200

2L

isso

wsk

a e

t al 2

00

6M

issed

Ex

po

su

re -

Co

ho

rt

Stu

die

s

Mis

sed

Ex

po

su

re -

Cas

e-C

on

tro

l

Be

tte

r E

xp

osu

re

Asses

sm

en

t



|______________________________________|



|_____________________|

Cohort

|___________________________|

Case-control






















cancerrdquo



2005 1

Surgeon Generals

Report 20062


(95 CI)

N Relative Risk

(95 CI)

All studies 19 125 (108-144) 21 120 (108-135)

Premenopausal

Women lt 50

14 168 (131-215) 11 164 (125-214)

Premenopausal

with lifetime

exposure

assessment

5 220 (169-287) 6 185 (119-287)


Balancing Concerns








Ed



0

50

100

150

200

250

USA 1994

Europe 1998

Sweden 1998

Germany 1998

China 1999

Germany 2000

China 2000

Canada 2001

Excess Lung

Cancer Risk

(Percentage)


Higher Exposure

Work Only -

Higher Exposure


+1-25

+35-220 +50-210























Teachers Cohort[48]

Adjusted HR

(95 CI)

Womenrsquos Health


Adjusted HR (95

CI)


exposure

100 100







126 (099-160) 132(104-167)





























Exposure



40+ cigday

138 (105-183)

174 (115-262)



205 (120-349)


gt20 cigday 183 (129-261)


Initiation 10-14 146 (111-193)

148 (103-213)


(premeno) 39 (15-99)


Hanaoka et al 2004



Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)






Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)

Pooled

Analysis

Never

active

100 100 100 100

lt20 105 (086-128) 123 (103-146) 091 (072-116) 110 (089-135)

gt20 149 (108-204) 142 (116-174) 129 (089-186) 088 (069-113)






initiation

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137)

Al-Delaimy(2004) 129 (097-171)

Reynolds (2004) 117 (105-130)

Lawlor (2004)

Gram (2005) 148 (103-213)

Olson (2005) 112 (092-136)

Cui (2006) 111 (097-128)

Ha (2007) 148 (077-284)

8 of 8 positive

4 of 8 Stat Sig




initiation

Longest duration

before pregnancy

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131)

Al-Delaimy(2004) 129 (097-171) 110 (080-152)

Reynolds (2004) 117 (105-130) 113 (100-125)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137)

Olson (2005) 112 (092-136) 121 (101-125)

Cui (2006) 111 (097-128) 113 (101-125)

Ha (2007) 148 (077-284) 178 (127-249)11

9 of 9 positive

4 of 9 Stat Sig




initiation

Longest duration

before pregnancy

Longest

duration

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189)

Ha (2007) 148 (077-284) 178 (127-249)11

6 of 6 positive

3 of 6 Stat Sig




initiation

Longest duration

Before pregnancy

Longest

duration

Highest pack-

years

Calle (1994) 159 (117-215) 138 (105-183)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133) 125 (106-147)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174) 146 (111-193)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138) 115 (096-137)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189) 117 (102-134)

Ha (2007) 148 (077-284) 178 (127-249)11


5 of 5 positive




First Author Year



Relative Risk

(95 CI)

Reynolds et al (2004) lt20 117 (105-130)

Olson et al (2005) lt19 112 (092-136)

Xue et al (2011) lt18 104 (099-111)

Cui et al (2006) lt16 111 (097-128)


Gram et al (2005) lt15 148 (103-213)

Ha et al (2007) lt15 148 (077-284)



















i
























bull History

bull Lung diseases


bull History

bull Lung disease



TOBACCO SMOKE








INFLAMMATION



LUNG CANCER




ndash COPD

ndash Lung cancer









times








bull History

bull Lung disease












bull History

bull Lung diseases

bull COPD









bull Findings






bull Interpretation







Follow up (y)

Po

stb

ron

cho

dila

tor

FEV

1 L

24

25

26

27

28

29

Screen 2 1 2 3 4 5

Sustained Quitters

Continuous Smokers



COPD










bull Asthma

Asthma








32 subjects


10 quit smoking

Lung cancer













200615517-523















Wen et al--2010




Kolappan Gopi--2002

Thank you




Cancer


Lung

Mouth and pharynx

Larynx

Esophagus

Stomach

Pancreas

Liver

Cervix

Bladder

Kidney

Colorectum

Breast




Body mass index






45-74 years







history from women




51 of the cohort




Heavy smokers (12)


Light smokers (88)





Men (n=27292) Women (n=34028)


Percent 422 214 364 913 25 62


Lung cancer


Never 100

1-12 432 (355-523)

13-22 661 (546-802)

23+ 949 (758-1188)

P for trend lt00001

Smoking status

Lung cancer

RR (95 CI)

Never 100

Former 224 (181-278)

Current 585 (499-687)







Body Mass

Index (kgm2)

Never

smokers

Former

smokers

Current

smokers

Adj HR

(95 CI)

Adj HR

(95 CI)

Adj HR

(95 CI)

lt20 100 100 100

20-lt24 102 (071-146) 092 (057-148) 081 (067-099)

24-lt28 072 (046-110) 101 (059-174) 062 (046-082)

28+ 081 (046-144) 097 (044-212) 050 (028-088)

P for trend 008 089 00001



Smoking

status



Never 100 100 100 100

Former 246

(140-432)

197

(148-262)

296

(184-476)

199

(088-452)

Current 721

(484-1075)

520

(422-641)

550

(364-832)

321

(158-651)





1-12 618

(398-958)

365

(282-473)

365

(212-628)

290

(115-727)

13-22 792

(501-1253)

639

(498-820)

541

(323-905)

221

(071-686)

23+ 1112

(660-1870)

853

(635-1150)

901

(504-1610)

637

(210-1930)

P trend lt00001 lt00001 lt00001 00001




of lung cancer





damage





weights



developed world



Obesity

Western diet

Physical inactivity

Smoking







GST enzymes







GSTP1 polymorphism







Smokers














us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang







Report Layout

Report Layout

Major Findings




6 SECONDS



Findings



ndexhtml





NCD Findings





Cancer deaths 22




tobacco use




Michael Thun

Richard Peto

Jillian Boreham

Alan Lopez

WCTOH

Singapore

March 2012


of Tobacco Control

20122196-101

Original WHO Model



Value of this Model




















Methods






amp GYTS





Results




countries





in women







US

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Australia

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Netherlands

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

UK

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female





Solution


men and women


specific data


in Men

0

10

20

30

40

50

60

70

0 10 20 30 40 50 60 70 80 90 100 110 120

0

5

10

15

20

25

30

35

40

of deaths caused by

smoking



male smokers

male deaths

Sub-Saharan Africa

Southeast Asia

China Norway




in Women

0

10

20

30

40

50

60

70

0 10 20 30 40 50 60 70 80 90 100 110 120

0

5

10

15

20

25

30

35

40

of deaths caused by



female smokers

female deaths

Sub-Saharan Africa




Australia

Conclusions










Thank You







Tobacco deaths 2000

Developed 2 million




countries

Tobacco deaths 2030

3 million

7 million




0

10

20

30

40

50

60

70

0 10 20 30 40 50 60 70 80 90 100

0

5

10

15

20

25

30

35

40

of deaths caused by

smoking



19601900 1920 1940 1980 2000

male smokers

female smokers

male deaths

female deaths



through 2005



0

10

20

30

40

50

60

1965

1974

1979

1983

1985

1990

1992

1994

1995

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

2009

2010

Year

Pre

vale

nce (

)



Men

Women

(52)

(34) (215)

(173)


0

10

20

30

40

50

60

70

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Women

0

10

20

30

40

50

60

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Pre

vale

nce


Australia

Men

0

10

20

30

40

50

60

70

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Women

0

10

20

30

40

50

60

70

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Pre

vale

nce




Romania

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Greece

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Poland

0

5

10

15

20

25

30

35

40

45

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Russia

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female



United Kingdom

United States

Canada

New Zealand

Australia







Greece

Italy

Spain





Community Medicine

Faculty of Medicine


March 23 2012


Singapore

Overview




Active smoking risk

Conclusions

Passive smoking

Secondhand smoke

Involuntary smoking











Acrylamide

Acrylonitrile

13-Butadiene

Isoprene

Nitromethane

Propylene Oxide


Vinyl chloride

4-Aminobiphenyl

Urethane

Benzene

Nitrobenzene

Benzo[a]pyrene

ortho-Toluidine

Dibenzo[ae]pyrene

Dibenzo[ai]pyrene

Dibenzo[al]pyrene






Mainstream Smoke

- Carbon monoxide

- Nitrogen Oxides

- Nicotine

25-15 times as much

37-128 times

13-21 as much

- Benzene

- Formaldehyde

- NNK

- Benz(a)pyrene

- Nickel

- Tar

8-10 times as much

50 times as much

1-22 times as much

25-20 times as much

13-30 times as much

11-157 times













01

1

10H

iray

am

a 199

2W

arte

nb

erg

et

al

200

0R

eyn

old

s e

t a

l 20

04

Ha

nao

ka e

t al

200

4S

an

dle

r e

t al 1

985

Millik

an

et

al 1

998

De

lfin

o e

t al

2000

Scru

bso

le e

t al

2004

Gam

mon

et a

l 200

4S

mit

h e

t al

1994

Mo

rab

ia e

t al 1

996

Zh

ao

et

al

1999

Jo

hn

so

n e

t al

200

0K

ro

pp

et

al

200

2L

isso

wsk

a e

t al 2

00

6M

issed

Ex

po

su

re -

Co

ho

rt

Stu

die

s

Mis

sed

Ex

po

su

re -

Cas

e-C

on

tro

l

Be

tte

r E

xp

osu

re

Asses

sm

en

t



|______________________________________|



|_____________________|

Cohort

|___________________________|

Case-control






















cancerrdquo



2005 1

Surgeon Generals

Report 20062


(95 CI)

N Relative Risk

(95 CI)

All studies 19 125 (108-144) 21 120 (108-135)

Premenopausal

Women lt 50

14 168 (131-215) 11 164 (125-214)

Premenopausal

with lifetime

exposure

assessment

5 220 (169-287) 6 185 (119-287)


Balancing Concerns








Ed



0

50

100

150

200

250

USA 1994

Europe 1998

Sweden 1998

Germany 1998

China 1999

Germany 2000

China 2000

Canada 2001

Excess Lung

Cancer Risk

(Percentage)


Higher Exposure

Work Only -

Higher Exposure


+1-25

+35-220 +50-210























Teachers Cohort[48]

Adjusted HR

(95 CI)

Womenrsquos Health


Adjusted HR (95

CI)


exposure

100 100







126 (099-160) 132(104-167)





























Exposure



40+ cigday

138 (105-183)

174 (115-262)



205 (120-349)


gt20 cigday 183 (129-261)


Initiation 10-14 146 (111-193)

148 (103-213)


(premeno) 39 (15-99)


Hanaoka et al 2004



Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)






Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)

Pooled

Analysis

Never

active

100 100 100 100

lt20 105 (086-128) 123 (103-146) 091 (072-116) 110 (089-135)

gt20 149 (108-204) 142 (116-174) 129 (089-186) 088 (069-113)






initiation

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137)

Al-Delaimy(2004) 129 (097-171)

Reynolds (2004) 117 (105-130)

Lawlor (2004)

Gram (2005) 148 (103-213)

Olson (2005) 112 (092-136)

Cui (2006) 111 (097-128)

Ha (2007) 148 (077-284)

8 of 8 positive

4 of 8 Stat Sig




initiation

Longest duration

before pregnancy

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131)

Al-Delaimy(2004) 129 (097-171) 110 (080-152)

Reynolds (2004) 117 (105-130) 113 (100-125)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137)

Olson (2005) 112 (092-136) 121 (101-125)

Cui (2006) 111 (097-128) 113 (101-125)

Ha (2007) 148 (077-284) 178 (127-249)11

9 of 9 positive

4 of 9 Stat Sig




initiation

Longest duration

before pregnancy

Longest

duration

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189)

Ha (2007) 148 (077-284) 178 (127-249)11

6 of 6 positive

3 of 6 Stat Sig




initiation

Longest duration

Before pregnancy

Longest

duration

Highest pack-

years

Calle (1994) 159 (117-215) 138 (105-183)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133) 125 (106-147)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174) 146 (111-193)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138) 115 (096-137)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189) 117 (102-134)

Ha (2007) 148 (077-284) 178 (127-249)11


5 of 5 positive




First Author Year



Relative Risk

(95 CI)

Reynolds et al (2004) lt20 117 (105-130)

Olson et al (2005) lt19 112 (092-136)

Xue et al (2011) lt18 104 (099-111)

Cui et al (2006) lt16 111 (097-128)


Gram et al (2005) lt15 148 (103-213)

Ha et al (2007) lt15 148 (077-284)



















i
























bull History

bull Lung diseases


bull History

bull Lung disease



TOBACCO SMOKE








INFLAMMATION



LUNG CANCER




ndash COPD

ndash Lung cancer









times








bull History

bull Lung disease












bull History

bull Lung diseases

bull COPD









bull Findings






bull Interpretation







Follow up (y)

Po

stb

ron

cho

dila

tor

FEV

1 L

24

25

26

27

28

29

Screen 2 1 2 3 4 5

Sustained Quitters

Continuous Smokers



COPD










bull Asthma

Asthma








32 subjects


10 quit smoking

Lung cancer













200615517-523















Wen et al--2010




Kolappan Gopi--2002

Thank you




Cancer


Lung

Mouth and pharynx

Larynx

Esophagus

Stomach

Pancreas

Liver

Cervix

Bladder

Kidney

Colorectum

Breast




Body mass index






45-74 years







history from women




51 of the cohort




Heavy smokers (12)


Light smokers (88)





Men (n=27292) Women (n=34028)


Percent 422 214 364 913 25 62


Lung cancer


Never 100

1-12 432 (355-523)

13-22 661 (546-802)

23+ 949 (758-1188)

P for trend lt00001

Smoking status

Lung cancer

RR (95 CI)

Never 100

Former 224 (181-278)

Current 585 (499-687)







Body Mass

Index (kgm2)

Never

smokers

Former

smokers

Current

smokers

Adj HR

(95 CI)

Adj HR

(95 CI)

Adj HR

(95 CI)

lt20 100 100 100

20-lt24 102 (071-146) 092 (057-148) 081 (067-099)

24-lt28 072 (046-110) 101 (059-174) 062 (046-082)

28+ 081 (046-144) 097 (044-212) 050 (028-088)

P for trend 008 089 00001



Smoking

status



Never 100 100 100 100

Former 246

(140-432)

197

(148-262)

296

(184-476)

199

(088-452)

Current 721

(484-1075)

520

(422-641)

550

(364-832)

321

(158-651)





1-12 618

(398-958)

365

(282-473)

365

(212-628)

290

(115-727)

13-22 792

(501-1253)

639

(498-820)

541

(323-905)

221

(071-686)

23+ 1112

(660-1870)

853

(635-1150)

901

(504-1610)

637

(210-1930)

P trend lt00001 lt00001 lt00001 00001




of lung cancer





damage





weights



developed world



Obesity

Western diet

Physical inactivity

Smoking







GST enzymes







GSTP1 polymorphism







Smokers














us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang







Report Layout

Major Findings




6 SECONDS



Findings



ndexhtml





NCD Findings





Cancer deaths 22




tobacco use




Michael Thun

Richard Peto

Jillian Boreham

Alan Lopez

WCTOH

Singapore

March 2012


of Tobacco Control

20122196-101

Original WHO Model



Value of this Model




















Methods






amp GYTS





Results




countries





in women







US

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Australia

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Netherlands

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

UK

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female





Solution


men and women


specific data


in Men

0

10

20

30

40

50

60

70

0 10 20 30 40 50 60 70 80 90 100 110 120

0

5

10

15

20

25

30

35

40

of deaths caused by

smoking



male smokers

male deaths

Sub-Saharan Africa

Southeast Asia

China Norway




in Women

0

10

20

30

40

50

60

70

0 10 20 30 40 50 60 70 80 90 100 110 120

0

5

10

15

20

25

30

35

40

of deaths caused by



female smokers

female deaths

Sub-Saharan Africa




Australia

Conclusions










Thank You







Tobacco deaths 2000

Developed 2 million




countries

Tobacco deaths 2030

3 million

7 million




0

10

20

30

40

50

60

70

0 10 20 30 40 50 60 70 80 90 100

0

5

10

15

20

25

30

35

40

of deaths caused by

smoking



19601900 1920 1940 1980 2000

male smokers

female smokers

male deaths

female deaths



through 2005



0

10

20

30

40

50

60

1965

1974

1979

1983

1985

1990

1992

1994

1995

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

2009

2010

Year

Pre

vale

nce (

)



Men

Women

(52)

(34) (215)

(173)


0

10

20

30

40

50

60

70

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Women

0

10

20

30

40

50

60

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Pre

vale

nce


Australia

Men

0

10

20

30

40

50

60

70

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Women

0

10

20

30

40

50

60

70

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Pre

vale

nce




Romania

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Greece

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Poland

0

5

10

15

20

25

30

35

40

45

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Russia

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female



United Kingdom

United States

Canada

New Zealand

Australia







Greece

Italy

Spain





Community Medicine

Faculty of Medicine


March 23 2012


Singapore

Overview




Active smoking risk

Conclusions

Passive smoking

Secondhand smoke

Involuntary smoking











Acrylamide

Acrylonitrile

13-Butadiene

Isoprene

Nitromethane

Propylene Oxide


Vinyl chloride

4-Aminobiphenyl

Urethane

Benzene

Nitrobenzene

Benzo[a]pyrene

ortho-Toluidine

Dibenzo[ae]pyrene

Dibenzo[ai]pyrene

Dibenzo[al]pyrene






Mainstream Smoke

- Carbon monoxide

- Nitrogen Oxides

- Nicotine

25-15 times as much

37-128 times

13-21 as much

- Benzene

- Formaldehyde

- NNK

- Benz(a)pyrene

- Nickel

- Tar

8-10 times as much

50 times as much

1-22 times as much

25-20 times as much

13-30 times as much

11-157 times













01

1

10H

iray

am

a 199

2W

arte

nb

erg

et

al

200

0R

eyn

old

s e

t a

l 20

04

Ha

nao

ka e

t al

200

4S

an

dle

r e

t al 1

985

Millik

an

et

al 1

998

De

lfin

o e

t al

2000

Scru

bso

le e

t al

2004

Gam

mon

et a

l 200

4S

mit

h e

t al

1994

Mo

rab

ia e

t al 1

996

Zh

ao

et

al

1999

Jo

hn

so

n e

t al

200

0K

ro

pp

et

al

200

2L

isso

wsk

a e

t al 2

00

6M

issed

Ex

po

su

re -

Co

ho

rt

Stu

die

s

Mis

sed

Ex

po

su

re -

Cas

e-C

on

tro

l

Be

tte

r E

xp

osu

re

Asses

sm

en

t



|______________________________________|



|_____________________|

Cohort

|___________________________|

Case-control






















cancerrdquo



2005 1

Surgeon Generals

Report 20062


(95 CI)

N Relative Risk

(95 CI)

All studies 19 125 (108-144) 21 120 (108-135)

Premenopausal

Women lt 50

14 168 (131-215) 11 164 (125-214)

Premenopausal

with lifetime

exposure

assessment

5 220 (169-287) 6 185 (119-287)


Balancing Concerns








Ed



0

50

100

150

200

250

USA 1994

Europe 1998

Sweden 1998

Germany 1998

China 1999

Germany 2000

China 2000

Canada 2001

Excess Lung

Cancer Risk

(Percentage)


Higher Exposure

Work Only -

Higher Exposure


+1-25

+35-220 +50-210























Teachers Cohort[48]

Adjusted HR

(95 CI)

Womenrsquos Health


Adjusted HR (95

CI)


exposure

100 100







126 (099-160) 132(104-167)





























Exposure



40+ cigday

138 (105-183)

174 (115-262)



205 (120-349)


gt20 cigday 183 (129-261)


Initiation 10-14 146 (111-193)

148 (103-213)


(premeno) 39 (15-99)


Hanaoka et al 2004



Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)






Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)

Pooled

Analysis

Never

active

100 100 100 100

lt20 105 (086-128) 123 (103-146) 091 (072-116) 110 (089-135)

gt20 149 (108-204) 142 (116-174) 129 (089-186) 088 (069-113)






initiation

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137)

Al-Delaimy(2004) 129 (097-171)

Reynolds (2004) 117 (105-130)

Lawlor (2004)

Gram (2005) 148 (103-213)

Olson (2005) 112 (092-136)

Cui (2006) 111 (097-128)

Ha (2007) 148 (077-284)

8 of 8 positive

4 of 8 Stat Sig




initiation

Longest duration

before pregnancy

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131)

Al-Delaimy(2004) 129 (097-171) 110 (080-152)

Reynolds (2004) 117 (105-130) 113 (100-125)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137)

Olson (2005) 112 (092-136) 121 (101-125)

Cui (2006) 111 (097-128) 113 (101-125)

Ha (2007) 148 (077-284) 178 (127-249)11

9 of 9 positive

4 of 9 Stat Sig




initiation

Longest duration

before pregnancy

Longest

duration

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189)

Ha (2007) 148 (077-284) 178 (127-249)11

6 of 6 positive

3 of 6 Stat Sig




initiation

Longest duration

Before pregnancy

Longest

duration

Highest pack-

years

Calle (1994) 159 (117-215) 138 (105-183)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133) 125 (106-147)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174) 146 (111-193)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138) 115 (096-137)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189) 117 (102-134)

Ha (2007) 148 (077-284) 178 (127-249)11


5 of 5 positive




First Author Year



Relative Risk

(95 CI)

Reynolds et al (2004) lt20 117 (105-130)

Olson et al (2005) lt19 112 (092-136)

Xue et al (2011) lt18 104 (099-111)

Cui et al (2006) lt16 111 (097-128)


Gram et al (2005) lt15 148 (103-213)

Ha et al (2007) lt15 148 (077-284)



















i
























bull History

bull Lung diseases


bull History

bull Lung disease



TOBACCO SMOKE








INFLAMMATION



LUNG CANCER




ndash COPD

ndash Lung cancer









times








bull History

bull Lung disease












bull History

bull Lung diseases

bull COPD









bull Findings






bull Interpretation







Follow up (y)

Po

stb

ron

cho

dila

tor

FEV

1 L

24

25

26

27

28

29

Screen 2 1 2 3 4 5

Sustained Quitters

Continuous Smokers



COPD










bull Asthma

Asthma








32 subjects


10 quit smoking

Lung cancer













200615517-523















Wen et al--2010




Kolappan Gopi--2002

Thank you




Cancer


Lung

Mouth and pharynx

Larynx

Esophagus

Stomach

Pancreas

Liver

Cervix

Bladder

Kidney

Colorectum

Breast




Body mass index






45-74 years







history from women




51 of the cohort




Heavy smokers (12)


Light smokers (88)





Men (n=27292) Women (n=34028)


Percent 422 214 364 913 25 62


Lung cancer


Never 100

1-12 432 (355-523)

13-22 661 (546-802)

23+ 949 (758-1188)

P for trend lt00001

Smoking status

Lung cancer

RR (95 CI)

Never 100

Former 224 (181-278)

Current 585 (499-687)







Body Mass

Index (kgm2)

Never

smokers

Former

smokers

Current

smokers

Adj HR

(95 CI)

Adj HR

(95 CI)

Adj HR

(95 CI)

lt20 100 100 100

20-lt24 102 (071-146) 092 (057-148) 081 (067-099)

24-lt28 072 (046-110) 101 (059-174) 062 (046-082)

28+ 081 (046-144) 097 (044-212) 050 (028-088)

P for trend 008 089 00001



Smoking

status



Never 100 100 100 100

Former 246

(140-432)

197

(148-262)

296

(184-476)

199

(088-452)

Current 721

(484-1075)

520

(422-641)

550

(364-832)

321

(158-651)





1-12 618

(398-958)

365

(282-473)

365

(212-628)

290

(115-727)

13-22 792

(501-1253)

639

(498-820)

541

(323-905)

221

(071-686)

23+ 1112

(660-1870)

853

(635-1150)

901

(504-1610)

637

(210-1930)

P trend lt00001 lt00001 lt00001 00001




of lung cancer





damage





weights



developed world



Obesity

Western diet

Physical inactivity

Smoking







GST enzymes







GSTP1 polymorphism







Smokers














us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang







Major Findings




6 SECONDS



Findings



ndexhtml





NCD Findings





Cancer deaths 22




tobacco use




Michael Thun

Richard Peto

Jillian Boreham

Alan Lopez

WCTOH

Singapore

March 2012


of Tobacco Control

20122196-101

Original WHO Model



Value of this Model




















Methods






amp GYTS





Results




countries





in women







US

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Australia

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Netherlands

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

UK

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female





Solution


men and women


specific data


in Men

0

10

20

30

40

50

60

70

0 10 20 30 40 50 60 70 80 90 100 110 120

0

5

10

15

20

25

30

35

40

of deaths caused by

smoking



male smokers

male deaths

Sub-Saharan Africa

Southeast Asia

China Norway




in Women

0

10

20

30

40

50

60

70

0 10 20 30 40 50 60 70 80 90 100 110 120

0

5

10

15

20

25

30

35

40

of deaths caused by



female smokers

female deaths

Sub-Saharan Africa




Australia

Conclusions










Thank You







Tobacco deaths 2000

Developed 2 million




countries

Tobacco deaths 2030

3 million

7 million




0

10

20

30

40

50

60

70

0 10 20 30 40 50 60 70 80 90 100

0

5

10

15

20

25

30

35

40

of deaths caused by

smoking



19601900 1920 1940 1980 2000

male smokers

female smokers

male deaths

female deaths



through 2005



0

10

20

30

40

50

60

1965

1974

1979

1983

1985

1990

1992

1994

1995

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

2009

2010

Year

Pre

vale

nce (

)



Men

Women

(52)

(34) (215)

(173)


0

10

20

30

40

50

60

70

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Women

0

10

20

30

40

50

60

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Pre

vale

nce


Australia

Men

0

10

20

30

40

50

60

70

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Women

0

10

20

30

40

50

60

70

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Pre

vale

nce




Romania

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Greece

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Poland

0

5

10

15

20

25

30

35

40

45

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Russia

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female



United Kingdom

United States

Canada

New Zealand

Australia







Greece

Italy

Spain





Community Medicine

Faculty of Medicine


March 23 2012


Singapore

Overview




Active smoking risk

Conclusions

Passive smoking

Secondhand smoke

Involuntary smoking











Acrylamide

Acrylonitrile

13-Butadiene

Isoprene

Nitromethane

Propylene Oxide


Vinyl chloride

4-Aminobiphenyl

Urethane

Benzene

Nitrobenzene

Benzo[a]pyrene

ortho-Toluidine

Dibenzo[ae]pyrene

Dibenzo[ai]pyrene

Dibenzo[al]pyrene






Mainstream Smoke

- Carbon monoxide

- Nitrogen Oxides

- Nicotine

25-15 times as much

37-128 times

13-21 as much

- Benzene

- Formaldehyde

- NNK

- Benz(a)pyrene

- Nickel

- Tar

8-10 times as much

50 times as much

1-22 times as much

25-20 times as much

13-30 times as much

11-157 times













01

1

10H

iray

am

a 199

2W

arte

nb

erg

et

al

200

0R

eyn

old

s e

t a

l 20

04

Ha

nao

ka e

t al

200

4S

an

dle

r e

t al 1

985

Millik

an

et

al 1

998

De

lfin

o e

t al

2000

Scru

bso

le e

t al

2004

Gam

mon

et a

l 200

4S

mit

h e

t al

1994

Mo

rab

ia e

t al 1

996

Zh

ao

et

al

1999

Jo

hn

so

n e

t al

200

0K

ro

pp

et

al

200

2L

isso

wsk

a e

t al 2

00

6M

issed

Ex

po

su

re -

Co

ho

rt

Stu

die

s

Mis

sed

Ex

po

su

re -

Cas

e-C

on

tro

l

Be

tte

r E

xp

osu

re

Asses

sm

en

t



|______________________________________|



|_____________________|

Cohort

|___________________________|

Case-control






















cancerrdquo



2005 1

Surgeon Generals

Report 20062


(95 CI)

N Relative Risk

(95 CI)

All studies 19 125 (108-144) 21 120 (108-135)

Premenopausal

Women lt 50

14 168 (131-215) 11 164 (125-214)

Premenopausal

with lifetime

exposure

assessment

5 220 (169-287) 6 185 (119-287)


Balancing Concerns








Ed



0

50

100

150

200

250

USA 1994

Europe 1998

Sweden 1998

Germany 1998

China 1999

Germany 2000

China 2000

Canada 2001

Excess Lung

Cancer Risk

(Percentage)


Higher Exposure

Work Only -

Higher Exposure


+1-25

+35-220 +50-210























Teachers Cohort[48]

Adjusted HR

(95 CI)

Womenrsquos Health


Adjusted HR (95

CI)


exposure

100 100







126 (099-160) 132(104-167)





























Exposure



40+ cigday

138 (105-183)

174 (115-262)



205 (120-349)


gt20 cigday 183 (129-261)


Initiation 10-14 146 (111-193)

148 (103-213)


(premeno) 39 (15-99)


Hanaoka et al 2004



Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)






Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)

Pooled

Analysis

Never

active

100 100 100 100

lt20 105 (086-128) 123 (103-146) 091 (072-116) 110 (089-135)

gt20 149 (108-204) 142 (116-174) 129 (089-186) 088 (069-113)






initiation

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137)

Al-Delaimy(2004) 129 (097-171)

Reynolds (2004) 117 (105-130)

Lawlor (2004)

Gram (2005) 148 (103-213)

Olson (2005) 112 (092-136)

Cui (2006) 111 (097-128)

Ha (2007) 148 (077-284)

8 of 8 positive

4 of 8 Stat Sig




initiation

Longest duration

before pregnancy

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131)

Al-Delaimy(2004) 129 (097-171) 110 (080-152)

Reynolds (2004) 117 (105-130) 113 (100-125)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137)

Olson (2005) 112 (092-136) 121 (101-125)

Cui (2006) 111 (097-128) 113 (101-125)

Ha (2007) 148 (077-284) 178 (127-249)11

9 of 9 positive

4 of 9 Stat Sig




initiation

Longest duration

before pregnancy

Longest

duration

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189)

Ha (2007) 148 (077-284) 178 (127-249)11

6 of 6 positive

3 of 6 Stat Sig




initiation

Longest duration

Before pregnancy

Longest

duration

Highest pack-

years

Calle (1994) 159 (117-215) 138 (105-183)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133) 125 (106-147)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174) 146 (111-193)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138) 115 (096-137)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189) 117 (102-134)

Ha (2007) 148 (077-284) 178 (127-249)11


5 of 5 positive




First Author Year



Relative Risk

(95 CI)

Reynolds et al (2004) lt20 117 (105-130)

Olson et al (2005) lt19 112 (092-136)

Xue et al (2011) lt18 104 (099-111)

Cui et al (2006) lt16 111 (097-128)


Gram et al (2005) lt15 148 (103-213)

Ha et al (2007) lt15 148 (077-284)



















i
























bull History

bull Lung diseases


bull History

bull Lung disease



TOBACCO SMOKE








INFLAMMATION



LUNG CANCER




ndash COPD

ndash Lung cancer









times








bull History

bull Lung disease












bull History

bull Lung diseases

bull COPD









bull Findings






bull Interpretation







Follow up (y)

Po

stb

ron

cho

dila

tor

FEV

1 L

24

25

26

27

28

29

Screen 2 1 2 3 4 5

Sustained Quitters

Continuous Smokers



COPD










bull Asthma

Asthma








32 subjects


10 quit smoking

Lung cancer













200615517-523















Wen et al--2010




Kolappan Gopi--2002

Thank you




Cancer


Lung

Mouth and pharynx

Larynx

Esophagus

Stomach

Pancreas

Liver

Cervix

Bladder

Kidney

Colorectum

Breast




Body mass index






45-74 years







history from women




51 of the cohort




Heavy smokers (12)


Light smokers (88)





Men (n=27292) Women (n=34028)


Percent 422 214 364 913 25 62


Lung cancer


Never 100

1-12 432 (355-523)

13-22 661 (546-802)

23+ 949 (758-1188)

P for trend lt00001

Smoking status

Lung cancer

RR (95 CI)

Never 100

Former 224 (181-278)

Current 585 (499-687)







Body Mass

Index (kgm2)

Never

smokers

Former

smokers

Current

smokers

Adj HR

(95 CI)

Adj HR

(95 CI)

Adj HR

(95 CI)

lt20 100 100 100

20-lt24 102 (071-146) 092 (057-148) 081 (067-099)

24-lt28 072 (046-110) 101 (059-174) 062 (046-082)

28+ 081 (046-144) 097 (044-212) 050 (028-088)

P for trend 008 089 00001



Smoking

status



Never 100 100 100 100

Former 246

(140-432)

197

(148-262)

296

(184-476)

199

(088-452)

Current 721

(484-1075)

520

(422-641)

550

(364-832)

321

(158-651)





1-12 618

(398-958)

365

(282-473)

365

(212-628)

290

(115-727)

13-22 792

(501-1253)

639

(498-820)

541

(323-905)

221

(071-686)

23+ 1112

(660-1870)

853

(635-1150)

901

(504-1610)

637

(210-1930)

P trend lt00001 lt00001 lt00001 00001




of lung cancer





damage





weights



developed world



Obesity

Western diet

Physical inactivity

Smoking







GST enzymes







GSTP1 polymorphism







Smokers














us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang







Findings



ndexhtml





NCD Findings





Cancer deaths 22




tobacco use




Michael Thun

Richard Peto

Jillian Boreham

Alan Lopez

WCTOH

Singapore

March 2012


of Tobacco Control

20122196-101

Original WHO Model



Value of this Model




















Methods






amp GYTS





Results




countries





in women







US

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Australia

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Netherlands

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

UK

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female





Solution


men and women


specific data


in Men

0

10

20

30

40

50

60

70

0 10 20 30 40 50 60 70 80 90 100 110 120

0

5

10

15

20

25

30

35

40

of deaths caused by

smoking



male smokers

male deaths

Sub-Saharan Africa

Southeast Asia

China Norway




in Women

0

10

20

30

40

50

60

70

0 10 20 30 40 50 60 70 80 90 100 110 120

0

5

10

15

20

25

30

35

40

of deaths caused by



female smokers

female deaths

Sub-Saharan Africa




Australia

Conclusions










Thank You







Tobacco deaths 2000

Developed 2 million




countries

Tobacco deaths 2030

3 million

7 million




0

10

20

30

40

50

60

70

0 10 20 30 40 50 60 70 80 90 100

0

5

10

15

20

25

30

35

40

of deaths caused by

smoking



19601900 1920 1940 1980 2000

male smokers

female smokers

male deaths

female deaths



through 2005



0

10

20

30

40

50

60

1965

1974

1979

1983

1985

1990

1992

1994

1995

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

2009

2010

Year

Pre

vale

nce (

)



Men

Women

(52)

(34) (215)

(173)


0

10

20

30

40

50

60

70

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Women

0

10

20

30

40

50

60

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Pre

vale

nce


Australia

Men

0

10

20

30

40

50

60

70

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Women

0

10

20

30

40

50

60

70

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Pre

vale

nce




Romania

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Greece

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Poland

0

5

10

15

20

25

30

35

40

45

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Russia

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female



United Kingdom

United States

Canada

New Zealand

Australia







Greece

Italy

Spain





Community Medicine

Faculty of Medicine


March 23 2012


Singapore

Overview




Active smoking risk

Conclusions

Passive smoking

Secondhand smoke

Involuntary smoking











Acrylamide

Acrylonitrile

13-Butadiene

Isoprene

Nitromethane

Propylene Oxide


Vinyl chloride

4-Aminobiphenyl

Urethane

Benzene

Nitrobenzene

Benzo[a]pyrene

ortho-Toluidine

Dibenzo[ae]pyrene

Dibenzo[ai]pyrene

Dibenzo[al]pyrene






Mainstream Smoke

- Carbon monoxide

- Nitrogen Oxides

- Nicotine

25-15 times as much

37-128 times

13-21 as much

- Benzene

- Formaldehyde

- NNK

- Benz(a)pyrene

- Nickel

- Tar

8-10 times as much

50 times as much

1-22 times as much

25-20 times as much

13-30 times as much

11-157 times













01

1

10H

iray

am

a 199

2W

arte

nb

erg

et

al

200

0R

eyn

old

s e

t a

l 20

04

Ha

nao

ka e

t al

200

4S

an

dle

r e

t al 1

985

Millik

an

et

al 1

998

De

lfin

o e

t al

2000

Scru

bso

le e

t al

2004

Gam

mon

et a

l 200

4S

mit

h e

t al

1994

Mo

rab

ia e

t al 1

996

Zh

ao

et

al

1999

Jo

hn

so

n e

t al

200

0K

ro

pp

et

al

200

2L

isso

wsk

a e

t al 2

00

6M

issed

Ex

po

su

re -

Co

ho

rt

Stu

die

s

Mis

sed

Ex

po

su

re -

Cas

e-C

on

tro

l

Be

tte

r E

xp

osu

re

Asses

sm

en

t



|______________________________________|



|_____________________|

Cohort

|___________________________|

Case-control






















cancerrdquo



2005 1

Surgeon Generals

Report 20062


(95 CI)

N Relative Risk

(95 CI)

All studies 19 125 (108-144) 21 120 (108-135)

Premenopausal

Women lt 50

14 168 (131-215) 11 164 (125-214)

Premenopausal

with lifetime

exposure

assessment

5 220 (169-287) 6 185 (119-287)


Balancing Concerns








Ed



0

50

100

150

200

250

USA 1994

Europe 1998

Sweden 1998

Germany 1998

China 1999

Germany 2000

China 2000

Canada 2001

Excess Lung

Cancer Risk

(Percentage)


Higher Exposure

Work Only -

Higher Exposure


+1-25

+35-220 +50-210























Teachers Cohort[48]

Adjusted HR

(95 CI)

Womenrsquos Health


Adjusted HR (95

CI)


exposure

100 100







126 (099-160) 132(104-167)





























Exposure



40+ cigday

138 (105-183)

174 (115-262)



205 (120-349)


gt20 cigday 183 (129-261)


Initiation 10-14 146 (111-193)

148 (103-213)


(premeno) 39 (15-99)


Hanaoka et al 2004



Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)






Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)

Pooled

Analysis

Never

active

100 100 100 100

lt20 105 (086-128) 123 (103-146) 091 (072-116) 110 (089-135)

gt20 149 (108-204) 142 (116-174) 129 (089-186) 088 (069-113)






initiation

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137)

Al-Delaimy(2004) 129 (097-171)

Reynolds (2004) 117 (105-130)

Lawlor (2004)

Gram (2005) 148 (103-213)

Olson (2005) 112 (092-136)

Cui (2006) 111 (097-128)

Ha (2007) 148 (077-284)

8 of 8 positive

4 of 8 Stat Sig




initiation

Longest duration

before pregnancy

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131)

Al-Delaimy(2004) 129 (097-171) 110 (080-152)

Reynolds (2004) 117 (105-130) 113 (100-125)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137)

Olson (2005) 112 (092-136) 121 (101-125)

Cui (2006) 111 (097-128) 113 (101-125)

Ha (2007) 148 (077-284) 178 (127-249)11

9 of 9 positive

4 of 9 Stat Sig




initiation

Longest duration

before pregnancy

Longest

duration

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189)

Ha (2007) 148 (077-284) 178 (127-249)11

6 of 6 positive

3 of 6 Stat Sig




initiation

Longest duration

Before pregnancy

Longest

duration

Highest pack-

years

Calle (1994) 159 (117-215) 138 (105-183)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133) 125 (106-147)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174) 146 (111-193)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138) 115 (096-137)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189) 117 (102-134)

Ha (2007) 148 (077-284) 178 (127-249)11


5 of 5 positive




First Author Year



Relative Risk

(95 CI)

Reynolds et al (2004) lt20 117 (105-130)

Olson et al (2005) lt19 112 (092-136)

Xue et al (2011) lt18 104 (099-111)

Cui et al (2006) lt16 111 (097-128)


Gram et al (2005) lt15 148 (103-213)

Ha et al (2007) lt15 148 (077-284)



















i
























bull History

bull Lung diseases


bull History

bull Lung disease



TOBACCO SMOKE








INFLAMMATION



LUNG CANCER




ndash COPD

ndash Lung cancer









times








bull History

bull Lung disease












bull History

bull Lung diseases

bull COPD









bull Findings






bull Interpretation







Follow up (y)

Po

stb

ron

cho

dila

tor

FEV

1 L

24

25

26

27

28

29

Screen 2 1 2 3 4 5

Sustained Quitters

Continuous Smokers



COPD










bull Asthma

Asthma








32 subjects


10 quit smoking

Lung cancer













200615517-523















Wen et al--2010




Kolappan Gopi--2002

Thank you




Cancer


Lung

Mouth and pharynx

Larynx

Esophagus

Stomach

Pancreas

Liver

Cervix

Bladder

Kidney

Colorectum

Breast




Body mass index






45-74 years







history from women




51 of the cohort




Heavy smokers (12)


Light smokers (88)





Men (n=27292) Women (n=34028)


Percent 422 214 364 913 25 62


Lung cancer


Never 100

1-12 432 (355-523)

13-22 661 (546-802)

23+ 949 (758-1188)

P for trend lt00001

Smoking status

Lung cancer

RR (95 CI)

Never 100

Former 224 (181-278)

Current 585 (499-687)







Body Mass

Index (kgm2)

Never

smokers

Former

smokers

Current

smokers

Adj HR

(95 CI)

Adj HR

(95 CI)

Adj HR

(95 CI)

lt20 100 100 100

20-lt24 102 (071-146) 092 (057-148) 081 (067-099)

24-lt28 072 (046-110) 101 (059-174) 062 (046-082)

28+ 081 (046-144) 097 (044-212) 050 (028-088)

P for trend 008 089 00001



Smoking

status



Never 100 100 100 100

Former 246

(140-432)

197

(148-262)

296

(184-476)

199

(088-452)

Current 721

(484-1075)

520

(422-641)

550

(364-832)

321

(158-651)





1-12 618

(398-958)

365

(282-473)

365

(212-628)

290

(115-727)

13-22 792

(501-1253)

639

(498-820)

541

(323-905)

221

(071-686)

23+ 1112

(660-1870)

853

(635-1150)

901

(504-1610)

637

(210-1930)

P trend lt00001 lt00001 lt00001 00001




of lung cancer





damage





weights



developed world



Obesity

Western diet

Physical inactivity

Smoking







GST enzymes







GSTP1 polymorphism







Smokers














us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang











NCD Findings





Cancer deaths 22




tobacco use




Michael Thun

Richard Peto

Jillian Boreham

Alan Lopez

WCTOH

Singapore

March 2012


of Tobacco Control

20122196-101

Original WHO Model



Value of this Model




















Methods






amp GYTS





Results




countries





in women







US

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Australia

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Netherlands

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

UK

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female





Solution


men and women


specific data


in Men

0

10

20

30

40

50

60

70

0 10 20 30 40 50 60 70 80 90 100 110 120

0

5

10

15

20

25

30

35

40

of deaths caused by

smoking



male smokers

male deaths

Sub-Saharan Africa

Southeast Asia

China Norway




in Women

0

10

20

30

40

50

60

70

0 10 20 30 40 50 60 70 80 90 100 110 120

0

5

10

15

20

25

30

35

40

of deaths caused by



female smokers

female deaths

Sub-Saharan Africa




Australia

Conclusions










Thank You







Tobacco deaths 2000

Developed 2 million




countries

Tobacco deaths 2030

3 million

7 million




0

10

20

30

40

50

60

70

0 10 20 30 40 50 60 70 80 90 100

0

5

10

15

20

25

30

35

40

of deaths caused by

smoking



19601900 1920 1940 1980 2000

male smokers

female smokers

male deaths

female deaths



through 2005



0

10

20

30

40

50

60

1965

1974

1979

1983

1985

1990

1992

1994

1995

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

2009

2010

Year

Pre

vale

nce (

)



Men

Women

(52)

(34) (215)

(173)


0

10

20

30

40

50

60

70

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Women

0

10

20

30

40

50

60

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Pre

vale

nce


Australia

Men

0

10

20

30

40

50

60

70

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Women

0

10

20

30

40

50

60

70

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Pre

vale

nce




Romania

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Greece

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Poland

0

5

10

15

20

25

30

35

40

45

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Russia

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female



United Kingdom

United States

Canada

New Zealand

Australia







Greece

Italy

Spain





Community Medicine

Faculty of Medicine


March 23 2012


Singapore

Overview




Active smoking risk

Conclusions

Passive smoking

Secondhand smoke

Involuntary smoking











Acrylamide

Acrylonitrile

13-Butadiene

Isoprene

Nitromethane

Propylene Oxide


Vinyl chloride

4-Aminobiphenyl

Urethane

Benzene

Nitrobenzene

Benzo[a]pyrene

ortho-Toluidine

Dibenzo[ae]pyrene

Dibenzo[ai]pyrene

Dibenzo[al]pyrene






Mainstream Smoke

- Carbon monoxide

- Nitrogen Oxides

- Nicotine

25-15 times as much

37-128 times

13-21 as much

- Benzene

- Formaldehyde

- NNK

- Benz(a)pyrene

- Nickel

- Tar

8-10 times as much

50 times as much

1-22 times as much

25-20 times as much

13-30 times as much

11-157 times













01

1

10H

iray

am

a 199

2W

arte

nb

erg

et

al

200

0R

eyn

old

s e

t a

l 20

04

Ha

nao

ka e

t al

200

4S

an

dle

r e

t al 1

985

Millik

an

et

al 1

998

De

lfin

o e

t al

2000

Scru

bso

le e

t al

2004

Gam

mon

et a

l 200

4S

mit

h e

t al

1994

Mo

rab

ia e

t al 1

996

Zh

ao

et

al

1999

Jo

hn

so

n e

t al

200

0K

ro

pp

et

al

200

2L

isso

wsk

a e

t al 2

00

6M

issed

Ex

po

su

re -

Co

ho

rt

Stu

die

s

Mis

sed

Ex

po

su

re -

Cas

e-C

on

tro

l

Be

tte

r E

xp

osu

re

Asses

sm

en

t



|______________________________________|



|_____________________|

Cohort

|___________________________|

Case-control






















cancerrdquo



2005 1

Surgeon Generals

Report 20062


(95 CI)

N Relative Risk

(95 CI)

All studies 19 125 (108-144) 21 120 (108-135)

Premenopausal

Women lt 50

14 168 (131-215) 11 164 (125-214)

Premenopausal

with lifetime

exposure

assessment

5 220 (169-287) 6 185 (119-287)


Balancing Concerns








Ed



0

50

100

150

200

250

USA 1994

Europe 1998

Sweden 1998

Germany 1998

China 1999

Germany 2000

China 2000

Canada 2001

Excess Lung

Cancer Risk

(Percentage)


Higher Exposure

Work Only -

Higher Exposure


+1-25

+35-220 +50-210























Teachers Cohort[48]

Adjusted HR

(95 CI)

Womenrsquos Health


Adjusted HR (95

CI)


exposure

100 100







126 (099-160) 132(104-167)





























Exposure



40+ cigday

138 (105-183)

174 (115-262)



205 (120-349)


gt20 cigday 183 (129-261)


Initiation 10-14 146 (111-193)

148 (103-213)


(premeno) 39 (15-99)


Hanaoka et al 2004



Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)






Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)

Pooled

Analysis

Never

active

100 100 100 100

lt20 105 (086-128) 123 (103-146) 091 (072-116) 110 (089-135)

gt20 149 (108-204) 142 (116-174) 129 (089-186) 088 (069-113)






initiation

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137)

Al-Delaimy(2004) 129 (097-171)

Reynolds (2004) 117 (105-130)

Lawlor (2004)

Gram (2005) 148 (103-213)

Olson (2005) 112 (092-136)

Cui (2006) 111 (097-128)

Ha (2007) 148 (077-284)

8 of 8 positive

4 of 8 Stat Sig




initiation

Longest duration

before pregnancy

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131)

Al-Delaimy(2004) 129 (097-171) 110 (080-152)

Reynolds (2004) 117 (105-130) 113 (100-125)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137)

Olson (2005) 112 (092-136) 121 (101-125)

Cui (2006) 111 (097-128) 113 (101-125)

Ha (2007) 148 (077-284) 178 (127-249)11

9 of 9 positive

4 of 9 Stat Sig




initiation

Longest duration

before pregnancy

Longest

duration

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189)

Ha (2007) 148 (077-284) 178 (127-249)11

6 of 6 positive

3 of 6 Stat Sig




initiation

Longest duration

Before pregnancy

Longest

duration

Highest pack-

years

Calle (1994) 159 (117-215) 138 (105-183)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133) 125 (106-147)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174) 146 (111-193)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138) 115 (096-137)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189) 117 (102-134)

Ha (2007) 148 (077-284) 178 (127-249)11


5 of 5 positive




First Author Year



Relative Risk

(95 CI)

Reynolds et al (2004) lt20 117 (105-130)

Olson et al (2005) lt19 112 (092-136)

Xue et al (2011) lt18 104 (099-111)

Cui et al (2006) lt16 111 (097-128)


Gram et al (2005) lt15 148 (103-213)

Ha et al (2007) lt15 148 (077-284)



















i
























bull History

bull Lung diseases


bull History

bull Lung disease



TOBACCO SMOKE








INFLAMMATION



LUNG CANCER




ndash COPD

ndash Lung cancer









times








bull History

bull Lung disease












bull History

bull Lung diseases

bull COPD









bull Findings






bull Interpretation







Follow up (y)

Po

stb

ron

cho

dila

tor

FEV

1 L

24

25

26

27

28

29

Screen 2 1 2 3 4 5

Sustained Quitters

Continuous Smokers



COPD










bull Asthma

Asthma








32 subjects


10 quit smoking

Lung cancer













200615517-523















Wen et al--2010




Kolappan Gopi--2002

Thank you




Cancer


Lung

Mouth and pharynx

Larynx

Esophagus

Stomach

Pancreas

Liver

Cervix

Bladder

Kidney

Colorectum

Breast




Body mass index






45-74 years







history from women




51 of the cohort




Heavy smokers (12)


Light smokers (88)





Men (n=27292) Women (n=34028)


Percent 422 214 364 913 25 62


Lung cancer


Never 100

1-12 432 (355-523)

13-22 661 (546-802)

23+ 949 (758-1188)

P for trend lt00001

Smoking status

Lung cancer

RR (95 CI)

Never 100

Former 224 (181-278)

Current 585 (499-687)







Body Mass

Index (kgm2)

Never

smokers

Former

smokers

Current

smokers

Adj HR

(95 CI)

Adj HR

(95 CI)

Adj HR

(95 CI)

lt20 100 100 100

20-lt24 102 (071-146) 092 (057-148) 081 (067-099)

24-lt28 072 (046-110) 101 (059-174) 062 (046-082)

28+ 081 (046-144) 097 (044-212) 050 (028-088)

P for trend 008 089 00001



Smoking

status



Never 100 100 100 100

Former 246

(140-432)

197

(148-262)

296

(184-476)

199

(088-452)

Current 721

(484-1075)

520

(422-641)

550

(364-832)

321

(158-651)





1-12 618

(398-958)

365

(282-473)

365

(212-628)

290

(115-727)

13-22 792

(501-1253)

639

(498-820)

541

(323-905)

221

(071-686)

23+ 1112

(660-1870)

853

(635-1150)

901

(504-1610)

637

(210-1930)

P trend lt00001 lt00001 lt00001 00001




of lung cancer





damage





weights



developed world



Obesity

Western diet

Physical inactivity

Smoking







GST enzymes







GSTP1 polymorphism







Smokers














us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang










Michael Thun

Richard Peto

Jillian Boreham

Alan Lopez

WCTOH

Singapore

March 2012


of Tobacco Control

20122196-101

Original WHO Model



Value of this Model




















Methods






amp GYTS





Results




countries





in women







US

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Australia

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Netherlands

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

UK

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female





Solution


men and women


specific data


in Men

0

10

20

30

40

50

60

70

0 10 20 30 40 50 60 70 80 90 100 110 120

0

5

10

15

20

25

30

35

40

of deaths caused by

smoking



male smokers

male deaths

Sub-Saharan Africa

Southeast Asia

China Norway




in Women

0

10

20

30

40

50

60

70

0 10 20 30 40 50 60 70 80 90 100 110 120

0

5

10

15

20

25

30

35

40

of deaths caused by



female smokers

female deaths

Sub-Saharan Africa




Australia

Conclusions










Thank You







Tobacco deaths 2000

Developed 2 million




countries

Tobacco deaths 2030

3 million

7 million




0

10

20

30

40

50

60

70

0 10 20 30 40 50 60 70 80 90 100

0

5

10

15

20

25

30

35

40

of deaths caused by

smoking



19601900 1920 1940 1980 2000

male smokers

female smokers

male deaths

female deaths



through 2005



0

10

20

30

40

50

60

1965

1974

1979

1983

1985

1990

1992

1994

1995

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

2009

2010

Year

Pre

vale

nce (

)



Men

Women

(52)

(34) (215)

(173)


0

10

20

30

40

50

60

70

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Women

0

10

20

30

40

50

60

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Pre

vale

nce


Australia

Men

0

10

20

30

40

50

60

70

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Women

0

10

20

30

40

50

60

70

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Pre

vale

nce




Romania

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Greece

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Poland

0

5

10

15

20

25

30

35

40

45

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Russia

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female



United Kingdom

United States

Canada

New Zealand

Australia







Greece

Italy

Spain





Community Medicine

Faculty of Medicine


March 23 2012


Singapore

Overview




Active smoking risk

Conclusions

Passive smoking

Secondhand smoke

Involuntary smoking











Acrylamide

Acrylonitrile

13-Butadiene

Isoprene

Nitromethane

Propylene Oxide


Vinyl chloride

4-Aminobiphenyl

Urethane

Benzene

Nitrobenzene

Benzo[a]pyrene

ortho-Toluidine

Dibenzo[ae]pyrene

Dibenzo[ai]pyrene

Dibenzo[al]pyrene






Mainstream Smoke

- Carbon monoxide

- Nitrogen Oxides

- Nicotine

25-15 times as much

37-128 times

13-21 as much

- Benzene

- Formaldehyde

- NNK

- Benz(a)pyrene

- Nickel

- Tar

8-10 times as much

50 times as much

1-22 times as much

25-20 times as much

13-30 times as much

11-157 times













01

1

10H

iray

am

a 199

2W

arte

nb

erg

et

al

200

0R

eyn

old

s e

t a

l 20

04

Ha

nao

ka e

t al

200

4S

an

dle

r e

t al 1

985

Millik

an

et

al 1

998

De

lfin

o e

t al

2000

Scru

bso

le e

t al

2004

Gam

mon

et a

l 200

4S

mit

h e

t al

1994

Mo

rab

ia e

t al 1

996

Zh

ao

et

al

1999

Jo

hn

so

n e

t al

200

0K

ro

pp

et

al

200

2L

isso

wsk

a e

t al 2

00

6M

issed

Ex

po

su

re -

Co

ho

rt

Stu

die

s

Mis

sed

Ex

po

su

re -

Cas

e-C

on

tro

l

Be

tte

r E

xp

osu

re

Asses

sm

en

t



|______________________________________|



|_____________________|

Cohort

|___________________________|

Case-control






















cancerrdquo



2005 1

Surgeon Generals

Report 20062


(95 CI)

N Relative Risk

(95 CI)

All studies 19 125 (108-144) 21 120 (108-135)

Premenopausal

Women lt 50

14 168 (131-215) 11 164 (125-214)

Premenopausal

with lifetime

exposure

assessment

5 220 (169-287) 6 185 (119-287)


Balancing Concerns








Ed



0

50

100

150

200

250

USA 1994

Europe 1998

Sweden 1998

Germany 1998

China 1999

Germany 2000

China 2000

Canada 2001

Excess Lung

Cancer Risk

(Percentage)


Higher Exposure

Work Only -

Higher Exposure


+1-25

+35-220 +50-210























Teachers Cohort[48]

Adjusted HR

(95 CI)

Womenrsquos Health


Adjusted HR (95

CI)


exposure

100 100







126 (099-160) 132(104-167)





























Exposure



40+ cigday

138 (105-183)

174 (115-262)



205 (120-349)


gt20 cigday 183 (129-261)


Initiation 10-14 146 (111-193)

148 (103-213)


(premeno) 39 (15-99)


Hanaoka et al 2004



Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)






Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)

Pooled

Analysis

Never

active

100 100 100 100

lt20 105 (086-128) 123 (103-146) 091 (072-116) 110 (089-135)

gt20 149 (108-204) 142 (116-174) 129 (089-186) 088 (069-113)






initiation

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137)

Al-Delaimy(2004) 129 (097-171)

Reynolds (2004) 117 (105-130)

Lawlor (2004)

Gram (2005) 148 (103-213)

Olson (2005) 112 (092-136)

Cui (2006) 111 (097-128)

Ha (2007) 148 (077-284)

8 of 8 positive

4 of 8 Stat Sig




initiation

Longest duration

before pregnancy

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131)

Al-Delaimy(2004) 129 (097-171) 110 (080-152)

Reynolds (2004) 117 (105-130) 113 (100-125)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137)

Olson (2005) 112 (092-136) 121 (101-125)

Cui (2006) 111 (097-128) 113 (101-125)

Ha (2007) 148 (077-284) 178 (127-249)11

9 of 9 positive

4 of 9 Stat Sig




initiation

Longest duration

before pregnancy

Longest

duration

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189)

Ha (2007) 148 (077-284) 178 (127-249)11

6 of 6 positive

3 of 6 Stat Sig




initiation

Longest duration

Before pregnancy

Longest

duration

Highest pack-

years

Calle (1994) 159 (117-215) 138 (105-183)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133) 125 (106-147)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174) 146 (111-193)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138) 115 (096-137)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189) 117 (102-134)

Ha (2007) 148 (077-284) 178 (127-249)11


5 of 5 positive




First Author Year



Relative Risk

(95 CI)

Reynolds et al (2004) lt20 117 (105-130)

Olson et al (2005) lt19 112 (092-136)

Xue et al (2011) lt18 104 (099-111)

Cui et al (2006) lt16 111 (097-128)


Gram et al (2005) lt15 148 (103-213)

Ha et al (2007) lt15 148 (077-284)



















i
























bull History

bull Lung diseases


bull History

bull Lung disease



TOBACCO SMOKE








INFLAMMATION



LUNG CANCER




ndash COPD

ndash Lung cancer









times








bull History

bull Lung disease












bull History

bull Lung diseases

bull COPD









bull Findings






bull Interpretation







Follow up (y)

Po

stb

ron

cho

dila

tor

FEV

1 L

24

25

26

27

28

29

Screen 2 1 2 3 4 5

Sustained Quitters

Continuous Smokers



COPD










bull Asthma

Asthma








32 subjects


10 quit smoking

Lung cancer













200615517-523















Wen et al--2010




Kolappan Gopi--2002

Thank you




Cancer


Lung

Mouth and pharynx

Larynx

Esophagus

Stomach

Pancreas

Liver

Cervix

Bladder

Kidney

Colorectum

Breast




Body mass index






45-74 years







history from women




51 of the cohort




Heavy smokers (12)


Light smokers (88)





Men (n=27292) Women (n=34028)


Percent 422 214 364 913 25 62


Lung cancer


Never 100

1-12 432 (355-523)

13-22 661 (546-802)

23+ 949 (758-1188)

P for trend lt00001

Smoking status

Lung cancer

RR (95 CI)

Never 100

Former 224 (181-278)

Current 585 (499-687)







Body Mass

Index (kgm2)

Never

smokers

Former

smokers

Current

smokers

Adj HR

(95 CI)

Adj HR

(95 CI)

Adj HR

(95 CI)

lt20 100 100 100

20-lt24 102 (071-146) 092 (057-148) 081 (067-099)

24-lt28 072 (046-110) 101 (059-174) 062 (046-082)

28+ 081 (046-144) 097 (044-212) 050 (028-088)

P for trend 008 089 00001



Smoking

status



Never 100 100 100 100

Former 246

(140-432)

197

(148-262)

296

(184-476)

199

(088-452)

Current 721

(484-1075)

520

(422-641)

550

(364-832)

321

(158-651)





1-12 618

(398-958)

365

(282-473)

365

(212-628)

290

(115-727)

13-22 792

(501-1253)

639

(498-820)

541

(323-905)

221

(071-686)

23+ 1112

(660-1870)

853

(635-1150)

901

(504-1610)

637

(210-1930)

P trend lt00001 lt00001 lt00001 00001




of lung cancer





damage





weights



developed world



Obesity

Western diet

Physical inactivity

Smoking







GST enzymes







GSTP1 polymorphism







Smokers














us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang








of Tobacco Control

20122196-101

Original WHO Model



Value of this Model




















Methods






amp GYTS





Results




countries





in women







US

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Australia

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Netherlands

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

UK

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female





Solution


men and women


specific data


in Men

0

10

20

30

40

50

60

70

0 10 20 30 40 50 60 70 80 90 100 110 120

0

5

10

15

20

25

30

35

40

of deaths caused by

smoking



male smokers

male deaths

Sub-Saharan Africa

Southeast Asia

China Norway




in Women

0

10

20

30

40

50

60

70

0 10 20 30 40 50 60 70 80 90 100 110 120

0

5

10

15

20

25

30

35

40

of deaths caused by



female smokers

female deaths

Sub-Saharan Africa




Australia

Conclusions










Thank You







Tobacco deaths 2000

Developed 2 million




countries

Tobacco deaths 2030

3 million

7 million




0

10

20

30

40

50

60

70

0 10 20 30 40 50 60 70 80 90 100

0

5

10

15

20

25

30

35

40

of deaths caused by

smoking



19601900 1920 1940 1980 2000

male smokers

female smokers

male deaths

female deaths



through 2005



0

10

20

30

40

50

60

1965

1974

1979

1983

1985

1990

1992

1994

1995

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

2009

2010

Year

Pre

vale

nce (

)



Men

Women

(52)

(34) (215)

(173)


0

10

20

30

40

50

60

70

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Women

0

10

20

30

40

50

60

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Pre

vale

nce


Australia

Men

0

10

20

30

40

50

60

70

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Women

0

10

20

30

40

50

60

70

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Pre

vale

nce




Romania

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Greece

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Poland

0

5

10

15

20

25

30

35

40

45

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Russia

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female



United Kingdom

United States

Canada

New Zealand

Australia







Greece

Italy

Spain





Community Medicine

Faculty of Medicine


March 23 2012


Singapore

Overview




Active smoking risk

Conclusions

Passive smoking

Secondhand smoke

Involuntary smoking











Acrylamide

Acrylonitrile

13-Butadiene

Isoprene

Nitromethane

Propylene Oxide


Vinyl chloride

4-Aminobiphenyl

Urethane

Benzene

Nitrobenzene

Benzo[a]pyrene

ortho-Toluidine

Dibenzo[ae]pyrene

Dibenzo[ai]pyrene

Dibenzo[al]pyrene






Mainstream Smoke

- Carbon monoxide

- Nitrogen Oxides

- Nicotine

25-15 times as much

37-128 times

13-21 as much

- Benzene

- Formaldehyde

- NNK

- Benz(a)pyrene

- Nickel

- Tar

8-10 times as much

50 times as much

1-22 times as much

25-20 times as much

13-30 times as much

11-157 times













01

1

10H

iray

am

a 199

2W

arte

nb

erg

et

al

200

0R

eyn

old

s e

t a

l 20

04

Ha

nao

ka e

t al

200

4S

an

dle

r e

t al 1

985

Millik

an

et

al 1

998

De

lfin

o e

t al

2000

Scru

bso

le e

t al

2004

Gam

mon

et a

l 200

4S

mit

h e

t al

1994

Mo

rab

ia e

t al 1

996

Zh

ao

et

al

1999

Jo

hn

so

n e

t al

200

0K

ro

pp

et

al

200

2L

isso

wsk

a e

t al 2

00

6M

issed

Ex

po

su

re -

Co

ho

rt

Stu

die

s

Mis

sed

Ex

po

su

re -

Cas

e-C

on

tro

l

Be

tte

r E

xp

osu

re

Asses

sm

en

t



|______________________________________|



|_____________________|

Cohort

|___________________________|

Case-control






















cancerrdquo



2005 1

Surgeon Generals

Report 20062


(95 CI)

N Relative Risk

(95 CI)

All studies 19 125 (108-144) 21 120 (108-135)

Premenopausal

Women lt 50

14 168 (131-215) 11 164 (125-214)

Premenopausal

with lifetime

exposure

assessment

5 220 (169-287) 6 185 (119-287)


Balancing Concerns








Ed



0

50

100

150

200

250

USA 1994

Europe 1998

Sweden 1998

Germany 1998

China 1999

Germany 2000

China 2000

Canada 2001

Excess Lung

Cancer Risk

(Percentage)


Higher Exposure

Work Only -

Higher Exposure


+1-25

+35-220 +50-210























Teachers Cohort[48]

Adjusted HR

(95 CI)

Womenrsquos Health


Adjusted HR (95

CI)


exposure

100 100







126 (099-160) 132(104-167)





























Exposure



40+ cigday

138 (105-183)

174 (115-262)



205 (120-349)


gt20 cigday 183 (129-261)


Initiation 10-14 146 (111-193)

148 (103-213)


(premeno) 39 (15-99)


Hanaoka et al 2004



Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)






Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)

Pooled

Analysis

Never

active

100 100 100 100

lt20 105 (086-128) 123 (103-146) 091 (072-116) 110 (089-135)

gt20 149 (108-204) 142 (116-174) 129 (089-186) 088 (069-113)






initiation

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137)

Al-Delaimy(2004) 129 (097-171)

Reynolds (2004) 117 (105-130)

Lawlor (2004)

Gram (2005) 148 (103-213)

Olson (2005) 112 (092-136)

Cui (2006) 111 (097-128)

Ha (2007) 148 (077-284)

8 of 8 positive

4 of 8 Stat Sig




initiation

Longest duration

before pregnancy

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131)

Al-Delaimy(2004) 129 (097-171) 110 (080-152)

Reynolds (2004) 117 (105-130) 113 (100-125)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137)

Olson (2005) 112 (092-136) 121 (101-125)

Cui (2006) 111 (097-128) 113 (101-125)

Ha (2007) 148 (077-284) 178 (127-249)11

9 of 9 positive

4 of 9 Stat Sig




initiation

Longest duration

before pregnancy

Longest

duration

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189)

Ha (2007) 148 (077-284) 178 (127-249)11

6 of 6 positive

3 of 6 Stat Sig




initiation

Longest duration

Before pregnancy

Longest

duration

Highest pack-

years

Calle (1994) 159 (117-215) 138 (105-183)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133) 125 (106-147)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174) 146 (111-193)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138) 115 (096-137)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189) 117 (102-134)

Ha (2007) 148 (077-284) 178 (127-249)11


5 of 5 positive




First Author Year



Relative Risk

(95 CI)

Reynolds et al (2004) lt20 117 (105-130)

Olson et al (2005) lt19 112 (092-136)

Xue et al (2011) lt18 104 (099-111)

Cui et al (2006) lt16 111 (097-128)


Gram et al (2005) lt15 148 (103-213)

Ha et al (2007) lt15 148 (077-284)



















i
























bull History

bull Lung diseases


bull History

bull Lung disease



TOBACCO SMOKE








INFLAMMATION



LUNG CANCER




ndash COPD

ndash Lung cancer









times








bull History

bull Lung disease












bull History

bull Lung diseases

bull COPD









bull Findings






bull Interpretation







Follow up (y)

Po

stb

ron

cho

dila

tor

FEV

1 L

24

25

26

27

28

29

Screen 2 1 2 3 4 5

Sustained Quitters

Continuous Smokers



COPD










bull Asthma

Asthma








32 subjects


10 quit smoking

Lung cancer













200615517-523















Wen et al--2010




Kolappan Gopi--2002

Thank you




Cancer


Lung

Mouth and pharynx

Larynx

Esophagus

Stomach

Pancreas

Liver

Cervix

Bladder

Kidney

Colorectum

Breast




Body mass index






45-74 years







history from women




51 of the cohort




Heavy smokers (12)


Light smokers (88)





Men (n=27292) Women (n=34028)


Percent 422 214 364 913 25 62


Lung cancer


Never 100

1-12 432 (355-523)

13-22 661 (546-802)

23+ 949 (758-1188)

P for trend lt00001

Smoking status

Lung cancer

RR (95 CI)

Never 100

Former 224 (181-278)

Current 585 (499-687)







Body Mass

Index (kgm2)

Never

smokers

Former

smokers

Current

smokers

Adj HR

(95 CI)

Adj HR

(95 CI)

Adj HR

(95 CI)

lt20 100 100 100

20-lt24 102 (071-146) 092 (057-148) 081 (067-099)

24-lt28 072 (046-110) 101 (059-174) 062 (046-082)

28+ 081 (046-144) 097 (044-212) 050 (028-088)

P for trend 008 089 00001



Smoking

status



Never 100 100 100 100

Former 246

(140-432)

197

(148-262)

296

(184-476)

199

(088-452)

Current 721

(484-1075)

520

(422-641)

550

(364-832)

321

(158-651)





1-12 618

(398-958)

365

(282-473)

365

(212-628)

290

(115-727)

13-22 792

(501-1253)

639

(498-820)

541

(323-905)

221

(071-686)

23+ 1112

(660-1870)

853

(635-1150)

901

(504-1610)

637

(210-1930)

P trend lt00001 lt00001 lt00001 00001




of lung cancer





damage





weights



developed world



Obesity

Western diet

Physical inactivity

Smoking







GST enzymes







GSTP1 polymorphism







Smokers














us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang







Original WHO Model



Value of this Model




















Methods






amp GYTS





Results




countries





in women







US

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Australia

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Netherlands

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

UK

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female





Solution


men and women


specific data


in Men

0

10

20

30

40

50

60

70

0 10 20 30 40 50 60 70 80 90 100 110 120

0

5

10

15

20

25

30

35

40

of deaths caused by

smoking



male smokers

male deaths

Sub-Saharan Africa

Southeast Asia

China Norway




in Women

0

10

20

30

40

50

60

70

0 10 20 30 40 50 60 70 80 90 100 110 120

0

5

10

15

20

25

30

35

40

of deaths caused by



female smokers

female deaths

Sub-Saharan Africa




Australia

Conclusions










Thank You







Tobacco deaths 2000

Developed 2 million




countries

Tobacco deaths 2030

3 million

7 million




0

10

20

30

40

50

60

70

0 10 20 30 40 50 60 70 80 90 100

0

5

10

15

20

25

30

35

40

of deaths caused by

smoking



19601900 1920 1940 1980 2000

male smokers

female smokers

male deaths

female deaths



through 2005



0

10

20

30

40

50

60

1965

1974

1979

1983

1985

1990

1992

1994

1995

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

2009

2010

Year

Pre

vale

nce (

)



Men

Women

(52)

(34) (215)

(173)


0

10

20

30

40

50

60

70

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Women

0

10

20

30

40

50

60

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Pre

vale

nce


Australia

Men

0

10

20

30

40

50

60

70

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Women

0

10

20

30

40

50

60

70

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Pre

vale

nce




Romania

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Greece

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Poland

0

5

10

15

20

25

30

35

40

45

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Russia

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female



United Kingdom

United States

Canada

New Zealand

Australia







Greece

Italy

Spain





Community Medicine

Faculty of Medicine


March 23 2012


Singapore

Overview




Active smoking risk

Conclusions

Passive smoking

Secondhand smoke

Involuntary smoking











Acrylamide

Acrylonitrile

13-Butadiene

Isoprene

Nitromethane

Propylene Oxide


Vinyl chloride

4-Aminobiphenyl

Urethane

Benzene

Nitrobenzene

Benzo[a]pyrene

ortho-Toluidine

Dibenzo[ae]pyrene

Dibenzo[ai]pyrene

Dibenzo[al]pyrene






Mainstream Smoke

- Carbon monoxide

- Nitrogen Oxides

- Nicotine

25-15 times as much

37-128 times

13-21 as much

- Benzene

- Formaldehyde

- NNK

- Benz(a)pyrene

- Nickel

- Tar

8-10 times as much

50 times as much

1-22 times as much

25-20 times as much

13-30 times as much

11-157 times













01

1

10H

iray

am

a 199

2W

arte

nb

erg

et

al

200

0R

eyn

old

s e

t a

l 20

04

Ha

nao

ka e

t al

200

4S

an

dle

r e

t al 1

985

Millik

an

et

al 1

998

De

lfin

o e

t al

2000

Scru

bso

le e

t al

2004

Gam

mon

et a

l 200

4S

mit

h e

t al

1994

Mo

rab

ia e

t al 1

996

Zh

ao

et

al

1999

Jo

hn

so

n e

t al

200

0K

ro

pp

et

al

200

2L

isso

wsk

a e

t al 2

00

6M

issed

Ex

po

su

re -

Co

ho

rt

Stu

die

s

Mis

sed

Ex

po

su

re -

Cas

e-C

on

tro

l

Be

tte

r E

xp

osu

re

Asses

sm

en

t



|______________________________________|



|_____________________|

Cohort

|___________________________|

Case-control






















cancerrdquo



2005 1

Surgeon Generals

Report 20062


(95 CI)

N Relative Risk

(95 CI)

All studies 19 125 (108-144) 21 120 (108-135)

Premenopausal

Women lt 50

14 168 (131-215) 11 164 (125-214)

Premenopausal

with lifetime

exposure

assessment

5 220 (169-287) 6 185 (119-287)


Balancing Concerns








Ed



0

50

100

150

200

250

USA 1994

Europe 1998

Sweden 1998

Germany 1998

China 1999

Germany 2000

China 2000

Canada 2001

Excess Lung

Cancer Risk

(Percentage)


Higher Exposure

Work Only -

Higher Exposure


+1-25

+35-220 +50-210























Teachers Cohort[48]

Adjusted HR

(95 CI)

Womenrsquos Health


Adjusted HR (95

CI)


exposure

100 100







126 (099-160) 132(104-167)





























Exposure



40+ cigday

138 (105-183)

174 (115-262)



205 (120-349)


gt20 cigday 183 (129-261)


Initiation 10-14 146 (111-193)

148 (103-213)


(premeno) 39 (15-99)


Hanaoka et al 2004



Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)






Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)

Pooled

Analysis

Never

active

100 100 100 100

lt20 105 (086-128) 123 (103-146) 091 (072-116) 110 (089-135)

gt20 149 (108-204) 142 (116-174) 129 (089-186) 088 (069-113)






initiation

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137)

Al-Delaimy(2004) 129 (097-171)

Reynolds (2004) 117 (105-130)

Lawlor (2004)

Gram (2005) 148 (103-213)

Olson (2005) 112 (092-136)

Cui (2006) 111 (097-128)

Ha (2007) 148 (077-284)

8 of 8 positive

4 of 8 Stat Sig




initiation

Longest duration

before pregnancy

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131)

Al-Delaimy(2004) 129 (097-171) 110 (080-152)

Reynolds (2004) 117 (105-130) 113 (100-125)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137)

Olson (2005) 112 (092-136) 121 (101-125)

Cui (2006) 111 (097-128) 113 (101-125)

Ha (2007) 148 (077-284) 178 (127-249)11

9 of 9 positive

4 of 9 Stat Sig




initiation

Longest duration

before pregnancy

Longest

duration

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189)

Ha (2007) 148 (077-284) 178 (127-249)11

6 of 6 positive

3 of 6 Stat Sig




initiation

Longest duration

Before pregnancy

Longest

duration

Highest pack-

years

Calle (1994) 159 (117-215) 138 (105-183)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133) 125 (106-147)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174) 146 (111-193)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138) 115 (096-137)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189) 117 (102-134)

Ha (2007) 148 (077-284) 178 (127-249)11


5 of 5 positive




First Author Year



Relative Risk

(95 CI)

Reynolds et al (2004) lt20 117 (105-130)

Olson et al (2005) lt19 112 (092-136)

Xue et al (2011) lt18 104 (099-111)

Cui et al (2006) lt16 111 (097-128)


Gram et al (2005) lt15 148 (103-213)

Ha et al (2007) lt15 148 (077-284)



















i
























bull History

bull Lung diseases


bull History

bull Lung disease



TOBACCO SMOKE








INFLAMMATION



LUNG CANCER




ndash COPD

ndash Lung cancer









times








bull History

bull Lung disease












bull History

bull Lung diseases

bull COPD









bull Findings






bull Interpretation







Follow up (y)

Po

stb

ron

cho

dila

tor

FEV

1 L

24

25

26

27

28

29

Screen 2 1 2 3 4 5

Sustained Quitters

Continuous Smokers



COPD










bull Asthma

Asthma








32 subjects


10 quit smoking

Lung cancer













200615517-523















Wen et al--2010




Kolappan Gopi--2002

Thank you




Cancer


Lung

Mouth and pharynx

Larynx

Esophagus

Stomach

Pancreas

Liver

Cervix

Bladder

Kidney

Colorectum

Breast




Body mass index






45-74 years







history from women




51 of the cohort




Heavy smokers (12)


Light smokers (88)





Men (n=27292) Women (n=34028)


Percent 422 214 364 913 25 62


Lung cancer


Never 100

1-12 432 (355-523)

13-22 661 (546-802)

23+ 949 (758-1188)

P for trend lt00001

Smoking status

Lung cancer

RR (95 CI)

Never 100

Former 224 (181-278)

Current 585 (499-687)







Body Mass

Index (kgm2)

Never

smokers

Former

smokers

Current

smokers

Adj HR

(95 CI)

Adj HR

(95 CI)

Adj HR

(95 CI)

lt20 100 100 100

20-lt24 102 (071-146) 092 (057-148) 081 (067-099)

24-lt28 072 (046-110) 101 (059-174) 062 (046-082)

28+ 081 (046-144) 097 (044-212) 050 (028-088)

P for trend 008 089 00001



Smoking

status



Never 100 100 100 100

Former 246

(140-432)

197

(148-262)

296

(184-476)

199

(088-452)

Current 721

(484-1075)

520

(422-641)

550

(364-832)

321

(158-651)





1-12 618

(398-958)

365

(282-473)

365

(212-628)

290

(115-727)

13-22 792

(501-1253)

639

(498-820)

541

(323-905)

221

(071-686)

23+ 1112

(660-1870)

853

(635-1150)

901

(504-1610)

637

(210-1930)

P trend lt00001 lt00001 lt00001 00001




of lung cancer





damage





weights



developed world



Obesity

Western diet

Physical inactivity

Smoking







GST enzymes







GSTP1 polymorphism







Smokers














us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang







Value of this Model




















Methods






amp GYTS





Results




countries





in women







US

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Australia

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Netherlands

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

UK

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female





Solution


men and women


specific data


in Men

0

10

20

30

40

50

60

70

0 10 20 30 40 50 60 70 80 90 100 110 120

0

5

10

15

20

25

30

35

40

of deaths caused by

smoking



male smokers

male deaths

Sub-Saharan Africa

Southeast Asia

China Norway




in Women

0

10

20

30

40

50

60

70

0 10 20 30 40 50 60 70 80 90 100 110 120

0

5

10

15

20

25

30

35

40

of deaths caused by



female smokers

female deaths

Sub-Saharan Africa




Australia

Conclusions










Thank You







Tobacco deaths 2000

Developed 2 million




countries

Tobacco deaths 2030

3 million

7 million




0

10

20

30

40

50

60

70

0 10 20 30 40 50 60 70 80 90 100

0

5

10

15

20

25

30

35

40

of deaths caused by

smoking



19601900 1920 1940 1980 2000

male smokers

female smokers

male deaths

female deaths



through 2005



0

10

20

30

40

50

60

1965

1974

1979

1983

1985

1990

1992

1994

1995

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

2009

2010

Year

Pre

vale

nce (

)



Men

Women

(52)

(34) (215)

(173)


0

10

20

30

40

50

60

70

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Women

0

10

20

30

40

50

60

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Pre

vale

nce


Australia

Men

0

10

20

30

40

50

60

70

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Women

0

10

20

30

40

50

60

70

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Pre

vale

nce




Romania

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Greece

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Poland

0

5

10

15

20

25

30

35

40

45

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Russia

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female



United Kingdom

United States

Canada

New Zealand

Australia







Greece

Italy

Spain





Community Medicine

Faculty of Medicine


March 23 2012


Singapore

Overview




Active smoking risk

Conclusions

Passive smoking

Secondhand smoke

Involuntary smoking











Acrylamide

Acrylonitrile

13-Butadiene

Isoprene

Nitromethane

Propylene Oxide


Vinyl chloride

4-Aminobiphenyl

Urethane

Benzene

Nitrobenzene

Benzo[a]pyrene

ortho-Toluidine

Dibenzo[ae]pyrene

Dibenzo[ai]pyrene

Dibenzo[al]pyrene






Mainstream Smoke

- Carbon monoxide

- Nitrogen Oxides

- Nicotine

25-15 times as much

37-128 times

13-21 as much

- Benzene

- Formaldehyde

- NNK

- Benz(a)pyrene

- Nickel

- Tar

8-10 times as much

50 times as much

1-22 times as much

25-20 times as much

13-30 times as much

11-157 times













01

1

10H

iray

am

a 199

2W

arte

nb

erg

et

al

200

0R

eyn

old

s e

t a

l 20

04

Ha

nao

ka e

t al

200

4S

an

dle

r e

t al 1

985

Millik

an

et

al 1

998

De

lfin

o e

t al

2000

Scru

bso

le e

t al

2004

Gam

mon

et a

l 200

4S

mit

h e

t al

1994

Mo

rab

ia e

t al 1

996

Zh

ao

et

al

1999

Jo

hn

so

n e

t al

200

0K

ro

pp

et

al

200

2L

isso

wsk

a e

t al 2

00

6M

issed

Ex

po

su

re -

Co

ho

rt

Stu

die

s

Mis

sed

Ex

po

su

re -

Cas

e-C

on

tro

l

Be

tte

r E

xp

osu

re

Asses

sm

en

t



|______________________________________|



|_____________________|

Cohort

|___________________________|

Case-control






















cancerrdquo



2005 1

Surgeon Generals

Report 20062


(95 CI)

N Relative Risk

(95 CI)

All studies 19 125 (108-144) 21 120 (108-135)

Premenopausal

Women lt 50

14 168 (131-215) 11 164 (125-214)

Premenopausal

with lifetime

exposure

assessment

5 220 (169-287) 6 185 (119-287)


Balancing Concerns








Ed



0

50

100

150

200

250

USA 1994

Europe 1998

Sweden 1998

Germany 1998

China 1999

Germany 2000

China 2000

Canada 2001

Excess Lung

Cancer Risk

(Percentage)


Higher Exposure

Work Only -

Higher Exposure


+1-25

+35-220 +50-210























Teachers Cohort[48]

Adjusted HR

(95 CI)

Womenrsquos Health


Adjusted HR (95

CI)


exposure

100 100







126 (099-160) 132(104-167)





























Exposure



40+ cigday

138 (105-183)

174 (115-262)



205 (120-349)


gt20 cigday 183 (129-261)


Initiation 10-14 146 (111-193)

148 (103-213)


(premeno) 39 (15-99)


Hanaoka et al 2004



Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)






Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)

Pooled

Analysis

Never

active

100 100 100 100

lt20 105 (086-128) 123 (103-146) 091 (072-116) 110 (089-135)

gt20 149 (108-204) 142 (116-174) 129 (089-186) 088 (069-113)






initiation

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137)

Al-Delaimy(2004) 129 (097-171)

Reynolds (2004) 117 (105-130)

Lawlor (2004)

Gram (2005) 148 (103-213)

Olson (2005) 112 (092-136)

Cui (2006) 111 (097-128)

Ha (2007) 148 (077-284)

8 of 8 positive

4 of 8 Stat Sig




initiation

Longest duration

before pregnancy

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131)

Al-Delaimy(2004) 129 (097-171) 110 (080-152)

Reynolds (2004) 117 (105-130) 113 (100-125)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137)

Olson (2005) 112 (092-136) 121 (101-125)

Cui (2006) 111 (097-128) 113 (101-125)

Ha (2007) 148 (077-284) 178 (127-249)11

9 of 9 positive

4 of 9 Stat Sig




initiation

Longest duration

before pregnancy

Longest

duration

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189)

Ha (2007) 148 (077-284) 178 (127-249)11

6 of 6 positive

3 of 6 Stat Sig




initiation

Longest duration

Before pregnancy

Longest

duration

Highest pack-

years

Calle (1994) 159 (117-215) 138 (105-183)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133) 125 (106-147)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174) 146 (111-193)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138) 115 (096-137)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189) 117 (102-134)

Ha (2007) 148 (077-284) 178 (127-249)11


5 of 5 positive




First Author Year



Relative Risk

(95 CI)

Reynolds et al (2004) lt20 117 (105-130)

Olson et al (2005) lt19 112 (092-136)

Xue et al (2011) lt18 104 (099-111)

Cui et al (2006) lt16 111 (097-128)


Gram et al (2005) lt15 148 (103-213)

Ha et al (2007) lt15 148 (077-284)



















i
























bull History

bull Lung diseases


bull History

bull Lung disease



TOBACCO SMOKE








INFLAMMATION



LUNG CANCER




ndash COPD

ndash Lung cancer









times








bull History

bull Lung disease












bull History

bull Lung diseases

bull COPD









bull Findings






bull Interpretation







Follow up (y)

Po

stb

ron

cho

dila

tor

FEV

1 L

24

25

26

27

28

29

Screen 2 1 2 3 4 5

Sustained Quitters

Continuous Smokers



COPD










bull Asthma

Asthma








32 subjects


10 quit smoking

Lung cancer













200615517-523















Wen et al--2010




Kolappan Gopi--2002

Thank you




Cancer


Lung

Mouth and pharynx

Larynx

Esophagus

Stomach

Pancreas

Liver

Cervix

Bladder

Kidney

Colorectum

Breast




Body mass index






45-74 years







history from women




51 of the cohort




Heavy smokers (12)


Light smokers (88)





Men (n=27292) Women (n=34028)


Percent 422 214 364 913 25 62


Lung cancer


Never 100

1-12 432 (355-523)

13-22 661 (546-802)

23+ 949 (758-1188)

P for trend lt00001

Smoking status

Lung cancer

RR (95 CI)

Never 100

Former 224 (181-278)

Current 585 (499-687)







Body Mass

Index (kgm2)

Never

smokers

Former

smokers

Current

smokers

Adj HR

(95 CI)

Adj HR

(95 CI)

Adj HR

(95 CI)

lt20 100 100 100

20-lt24 102 (071-146) 092 (057-148) 081 (067-099)

24-lt28 072 (046-110) 101 (059-174) 062 (046-082)

28+ 081 (046-144) 097 (044-212) 050 (028-088)

P for trend 008 089 00001



Smoking

status



Never 100 100 100 100

Former 246

(140-432)

197

(148-262)

296

(184-476)

199

(088-452)

Current 721

(484-1075)

520

(422-641)

550

(364-832)

321

(158-651)





1-12 618

(398-958)

365

(282-473)

365

(212-628)

290

(115-727)

13-22 792

(501-1253)

639

(498-820)

541

(323-905)

221

(071-686)

23+ 1112

(660-1870)

853

(635-1150)

901

(504-1610)

637

(210-1930)

P trend lt00001 lt00001 lt00001 00001




of lung cancer





damage





weights



developed world



Obesity

Western diet

Physical inactivity

Smoking







GST enzymes







GSTP1 polymorphism







Smokers














us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang
















Methods






amp GYTS





Results




countries





in women







US

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Australia

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Netherlands

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

UK

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female





Solution


men and women


specific data


in Men

0

10

20

30

40

50

60

70

0 10 20 30 40 50 60 70 80 90 100 110 120

0

5

10

15

20

25

30

35

40

of deaths caused by

smoking



male smokers

male deaths

Sub-Saharan Africa

Southeast Asia

China Norway




in Women

0

10

20

30

40

50

60

70

0 10 20 30 40 50 60 70 80 90 100 110 120

0

5

10

15

20

25

30

35

40

of deaths caused by



female smokers

female deaths

Sub-Saharan Africa




Australia

Conclusions










Thank You







Tobacco deaths 2000

Developed 2 million




countries

Tobacco deaths 2030

3 million

7 million




0

10

20

30

40

50

60

70

0 10 20 30 40 50 60 70 80 90 100

0

5

10

15

20

25

30

35

40

of deaths caused by

smoking



19601900 1920 1940 1980 2000

male smokers

female smokers

male deaths

female deaths



through 2005



0

10

20

30

40

50

60

1965

1974

1979

1983

1985

1990

1992

1994

1995

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

2009

2010

Year

Pre

vale

nce (

)



Men

Women

(52)

(34) (215)

(173)


0

10

20

30

40

50

60

70

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Women

0

10

20

30

40

50

60

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Pre

vale

nce


Australia

Men

0

10

20

30

40

50

60

70

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Women

0

10

20

30

40

50

60

70

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Pre

vale

nce




Romania

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Greece

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Poland

0

5

10

15

20

25

30

35

40

45

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Russia

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female



United Kingdom

United States

Canada

New Zealand

Australia







Greece

Italy

Spain





Community Medicine

Faculty of Medicine


March 23 2012


Singapore

Overview




Active smoking risk

Conclusions

Passive smoking

Secondhand smoke

Involuntary smoking











Acrylamide

Acrylonitrile

13-Butadiene

Isoprene

Nitromethane

Propylene Oxide


Vinyl chloride

4-Aminobiphenyl

Urethane

Benzene

Nitrobenzene

Benzo[a]pyrene

ortho-Toluidine

Dibenzo[ae]pyrene

Dibenzo[ai]pyrene

Dibenzo[al]pyrene






Mainstream Smoke

- Carbon monoxide

- Nitrogen Oxides

- Nicotine

25-15 times as much

37-128 times

13-21 as much

- Benzene

- Formaldehyde

- NNK

- Benz(a)pyrene

- Nickel

- Tar

8-10 times as much

50 times as much

1-22 times as much

25-20 times as much

13-30 times as much

11-157 times













01

1

10H

iray

am

a 199

2W

arte

nb

erg

et

al

200

0R

eyn

old

s e

t a

l 20

04

Ha

nao

ka e

t al

200

4S

an

dle

r e

t al 1

985

Millik

an

et

al 1

998

De

lfin

o e

t al

2000

Scru

bso

le e

t al

2004

Gam

mon

et a

l 200

4S

mit

h e

t al

1994

Mo

rab

ia e

t al 1

996

Zh

ao

et

al

1999

Jo

hn

so

n e

t al

200

0K

ro

pp

et

al

200

2L

isso

wsk

a e

t al 2

00

6M

issed

Ex

po

su

re -

Co

ho

rt

Stu

die

s

Mis

sed

Ex

po

su

re -

Cas

e-C

on

tro

l

Be

tte

r E

xp

osu

re

Asses

sm

en

t



|______________________________________|



|_____________________|

Cohort

|___________________________|

Case-control






















cancerrdquo



2005 1

Surgeon Generals

Report 20062


(95 CI)

N Relative Risk

(95 CI)

All studies 19 125 (108-144) 21 120 (108-135)

Premenopausal

Women lt 50

14 168 (131-215) 11 164 (125-214)

Premenopausal

with lifetime

exposure

assessment

5 220 (169-287) 6 185 (119-287)


Balancing Concerns








Ed



0

50

100

150

200

250

USA 1994

Europe 1998

Sweden 1998

Germany 1998

China 1999

Germany 2000

China 2000

Canada 2001

Excess Lung

Cancer Risk

(Percentage)


Higher Exposure

Work Only -

Higher Exposure


+1-25

+35-220 +50-210























Teachers Cohort[48]

Adjusted HR

(95 CI)

Womenrsquos Health


Adjusted HR (95

CI)


exposure

100 100







126 (099-160) 132(104-167)





























Exposure



40+ cigday

138 (105-183)

174 (115-262)



205 (120-349)


gt20 cigday 183 (129-261)


Initiation 10-14 146 (111-193)

148 (103-213)


(premeno) 39 (15-99)


Hanaoka et al 2004



Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)






Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)

Pooled

Analysis

Never

active

100 100 100 100

lt20 105 (086-128) 123 (103-146) 091 (072-116) 110 (089-135)

gt20 149 (108-204) 142 (116-174) 129 (089-186) 088 (069-113)






initiation

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137)

Al-Delaimy(2004) 129 (097-171)

Reynolds (2004) 117 (105-130)

Lawlor (2004)

Gram (2005) 148 (103-213)

Olson (2005) 112 (092-136)

Cui (2006) 111 (097-128)

Ha (2007) 148 (077-284)

8 of 8 positive

4 of 8 Stat Sig




initiation

Longest duration

before pregnancy

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131)

Al-Delaimy(2004) 129 (097-171) 110 (080-152)

Reynolds (2004) 117 (105-130) 113 (100-125)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137)

Olson (2005) 112 (092-136) 121 (101-125)

Cui (2006) 111 (097-128) 113 (101-125)

Ha (2007) 148 (077-284) 178 (127-249)11

9 of 9 positive

4 of 9 Stat Sig




initiation

Longest duration

before pregnancy

Longest

duration

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189)

Ha (2007) 148 (077-284) 178 (127-249)11

6 of 6 positive

3 of 6 Stat Sig




initiation

Longest duration

Before pregnancy

Longest

duration

Highest pack-

years

Calle (1994) 159 (117-215) 138 (105-183)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133) 125 (106-147)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174) 146 (111-193)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138) 115 (096-137)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189) 117 (102-134)

Ha (2007) 148 (077-284) 178 (127-249)11


5 of 5 positive




First Author Year



Relative Risk

(95 CI)

Reynolds et al (2004) lt20 117 (105-130)

Olson et al (2005) lt19 112 (092-136)

Xue et al (2011) lt18 104 (099-111)

Cui et al (2006) lt16 111 (097-128)


Gram et al (2005) lt15 148 (103-213)

Ha et al (2007) lt15 148 (077-284)



















i
























bull History

bull Lung diseases


bull History

bull Lung disease



TOBACCO SMOKE








INFLAMMATION



LUNG CANCER




ndash COPD

ndash Lung cancer









times








bull History

bull Lung disease












bull History

bull Lung diseases

bull COPD









bull Findings






bull Interpretation







Follow up (y)

Po

stb

ron

cho

dila

tor

FEV

1 L

24

25

26

27

28

29

Screen 2 1 2 3 4 5

Sustained Quitters

Continuous Smokers



COPD










bull Asthma

Asthma








32 subjects


10 quit smoking

Lung cancer













200615517-523















Wen et al--2010




Kolappan Gopi--2002

Thank you




Cancer


Lung

Mouth and pharynx

Larynx

Esophagus

Stomach

Pancreas

Liver

Cervix

Bladder

Kidney

Colorectum

Breast




Body mass index






45-74 years







history from women




51 of the cohort




Heavy smokers (12)


Light smokers (88)





Men (n=27292) Women (n=34028)


Percent 422 214 364 913 25 62


Lung cancer


Never 100

1-12 432 (355-523)

13-22 661 (546-802)

23+ 949 (758-1188)

P for trend lt00001

Smoking status

Lung cancer

RR (95 CI)

Never 100

Former 224 (181-278)

Current 585 (499-687)







Body Mass

Index (kgm2)

Never

smokers

Former

smokers

Current

smokers

Adj HR

(95 CI)

Adj HR

(95 CI)

Adj HR

(95 CI)

lt20 100 100 100

20-lt24 102 (071-146) 092 (057-148) 081 (067-099)

24-lt28 072 (046-110) 101 (059-174) 062 (046-082)

28+ 081 (046-144) 097 (044-212) 050 (028-088)

P for trend 008 089 00001



Smoking

status



Never 100 100 100 100

Former 246

(140-432)

197

(148-262)

296

(184-476)

199

(088-452)

Current 721

(484-1075)

520

(422-641)

550

(364-832)

321

(158-651)





1-12 618

(398-958)

365

(282-473)

365

(212-628)

290

(115-727)

13-22 792

(501-1253)

639

(498-820)

541

(323-905)

221

(071-686)

23+ 1112

(660-1870)

853

(635-1150)

901

(504-1610)

637

(210-1930)

P trend lt00001 lt00001 lt00001 00001




of lung cancer





damage





weights



developed world



Obesity

Western diet

Physical inactivity

Smoking







GST enzymes







GSTP1 polymorphism







Smokers














us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang







Results




countries





in women







US

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Australia

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Netherlands

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

UK

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female





Solution


men and women


specific data


in Men

0

10

20

30

40

50

60

70

0 10 20 30 40 50 60 70 80 90 100 110 120

0

5

10

15

20

25

30

35

40

of deaths caused by

smoking



male smokers

male deaths

Sub-Saharan Africa

Southeast Asia

China Norway




in Women

0

10

20

30

40

50

60

70

0 10 20 30 40 50 60 70 80 90 100 110 120

0

5

10

15

20

25

30

35

40

of deaths caused by



female smokers

female deaths

Sub-Saharan Africa




Australia

Conclusions










Thank You







Tobacco deaths 2000

Developed 2 million




countries

Tobacco deaths 2030

3 million

7 million




0

10

20

30

40

50

60

70

0 10 20 30 40 50 60 70 80 90 100

0

5

10

15

20

25

30

35

40

of deaths caused by

smoking



19601900 1920 1940 1980 2000

male smokers

female smokers

male deaths

female deaths



through 2005



0

10

20

30

40

50

60

1965

1974

1979

1983

1985

1990

1992

1994

1995

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

2009

2010

Year

Pre

vale

nce (

)



Men

Women

(52)

(34) (215)

(173)


0

10

20

30

40

50

60

70

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Women

0

10

20

30

40

50

60

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Pre

vale

nce


Australia

Men

0

10

20

30

40

50

60

70

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Women

0

10

20

30

40

50

60

70

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Pre

vale

nce




Romania

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Greece

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Poland

0

5

10

15

20

25

30

35

40

45

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Russia

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female



United Kingdom

United States

Canada

New Zealand

Australia







Greece

Italy

Spain





Community Medicine

Faculty of Medicine


March 23 2012


Singapore

Overview




Active smoking risk

Conclusions

Passive smoking

Secondhand smoke

Involuntary smoking











Acrylamide

Acrylonitrile

13-Butadiene

Isoprene

Nitromethane

Propylene Oxide


Vinyl chloride

4-Aminobiphenyl

Urethane

Benzene

Nitrobenzene

Benzo[a]pyrene

ortho-Toluidine

Dibenzo[ae]pyrene

Dibenzo[ai]pyrene

Dibenzo[al]pyrene






Mainstream Smoke

- Carbon monoxide

- Nitrogen Oxides

- Nicotine

25-15 times as much

37-128 times

13-21 as much

- Benzene

- Formaldehyde

- NNK

- Benz(a)pyrene

- Nickel

- Tar

8-10 times as much

50 times as much

1-22 times as much

25-20 times as much

13-30 times as much

11-157 times













01

1

10H

iray

am

a 199

2W

arte

nb

erg

et

al

200

0R

eyn

old

s e

t a

l 20

04

Ha

nao

ka e

t al

200

4S

an

dle

r e

t al 1

985

Millik

an

et

al 1

998

De

lfin

o e

t al

2000

Scru

bso

le e

t al

2004

Gam

mon

et a

l 200

4S

mit

h e

t al

1994

Mo

rab

ia e

t al 1

996

Zh

ao

et

al

1999

Jo

hn

so

n e

t al

200

0K

ro

pp

et

al

200

2L

isso

wsk

a e

t al 2

00

6M

issed

Ex

po

su

re -

Co

ho

rt

Stu

die

s

Mis

sed

Ex

po

su

re -

Cas

e-C

on

tro

l

Be

tte

r E

xp

osu

re

Asses

sm

en

t



|______________________________________|



|_____________________|

Cohort

|___________________________|

Case-control






















cancerrdquo



2005 1

Surgeon Generals

Report 20062


(95 CI)

N Relative Risk

(95 CI)

All studies 19 125 (108-144) 21 120 (108-135)

Premenopausal

Women lt 50

14 168 (131-215) 11 164 (125-214)

Premenopausal

with lifetime

exposure

assessment

5 220 (169-287) 6 185 (119-287)


Balancing Concerns








Ed



0

50

100

150

200

250

USA 1994

Europe 1998

Sweden 1998

Germany 1998

China 1999

Germany 2000

China 2000

Canada 2001

Excess Lung

Cancer Risk

(Percentage)


Higher Exposure

Work Only -

Higher Exposure


+1-25

+35-220 +50-210























Teachers Cohort[48]

Adjusted HR

(95 CI)

Womenrsquos Health


Adjusted HR (95

CI)


exposure

100 100







126 (099-160) 132(104-167)





























Exposure



40+ cigday

138 (105-183)

174 (115-262)



205 (120-349)


gt20 cigday 183 (129-261)


Initiation 10-14 146 (111-193)

148 (103-213)


(premeno) 39 (15-99)


Hanaoka et al 2004



Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)






Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)

Pooled

Analysis

Never

active

100 100 100 100

lt20 105 (086-128) 123 (103-146) 091 (072-116) 110 (089-135)

gt20 149 (108-204) 142 (116-174) 129 (089-186) 088 (069-113)






initiation

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137)

Al-Delaimy(2004) 129 (097-171)

Reynolds (2004) 117 (105-130)

Lawlor (2004)

Gram (2005) 148 (103-213)

Olson (2005) 112 (092-136)

Cui (2006) 111 (097-128)

Ha (2007) 148 (077-284)

8 of 8 positive

4 of 8 Stat Sig




initiation

Longest duration

before pregnancy

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131)

Al-Delaimy(2004) 129 (097-171) 110 (080-152)

Reynolds (2004) 117 (105-130) 113 (100-125)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137)

Olson (2005) 112 (092-136) 121 (101-125)

Cui (2006) 111 (097-128) 113 (101-125)

Ha (2007) 148 (077-284) 178 (127-249)11

9 of 9 positive

4 of 9 Stat Sig




initiation

Longest duration

before pregnancy

Longest

duration

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189)

Ha (2007) 148 (077-284) 178 (127-249)11

6 of 6 positive

3 of 6 Stat Sig




initiation

Longest duration

Before pregnancy

Longest

duration

Highest pack-

years

Calle (1994) 159 (117-215) 138 (105-183)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133) 125 (106-147)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174) 146 (111-193)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138) 115 (096-137)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189) 117 (102-134)

Ha (2007) 148 (077-284) 178 (127-249)11


5 of 5 positive




First Author Year



Relative Risk

(95 CI)

Reynolds et al (2004) lt20 117 (105-130)

Olson et al (2005) lt19 112 (092-136)

Xue et al (2011) lt18 104 (099-111)

Cui et al (2006) lt16 111 (097-128)


Gram et al (2005) lt15 148 (103-213)

Ha et al (2007) lt15 148 (077-284)



















i
























bull History

bull Lung diseases


bull History

bull Lung disease



TOBACCO SMOKE








INFLAMMATION



LUNG CANCER




ndash COPD

ndash Lung cancer









times








bull History

bull Lung disease












bull History

bull Lung diseases

bull COPD









bull Findings






bull Interpretation







Follow up (y)

Po

stb

ron

cho

dila

tor

FEV

1 L

24

25

26

27

28

29

Screen 2 1 2 3 4 5

Sustained Quitters

Continuous Smokers



COPD










bull Asthma

Asthma








32 subjects


10 quit smoking

Lung cancer













200615517-523















Wen et al--2010




Kolappan Gopi--2002

Thank you




Cancer


Lung

Mouth and pharynx

Larynx

Esophagus

Stomach

Pancreas

Liver

Cervix

Bladder

Kidney

Colorectum

Breast




Body mass index






45-74 years







history from women




51 of the cohort




Heavy smokers (12)


Light smokers (88)





Men (n=27292) Women (n=34028)


Percent 422 214 364 913 25 62


Lung cancer


Never 100

1-12 432 (355-523)

13-22 661 (546-802)

23+ 949 (758-1188)

P for trend lt00001

Smoking status

Lung cancer

RR (95 CI)

Never 100

Former 224 (181-278)

Current 585 (499-687)







Body Mass

Index (kgm2)

Never

smokers

Former

smokers

Current

smokers

Adj HR

(95 CI)

Adj HR

(95 CI)

Adj HR

(95 CI)

lt20 100 100 100

20-lt24 102 (071-146) 092 (057-148) 081 (067-099)

24-lt28 072 (046-110) 101 (059-174) 062 (046-082)

28+ 081 (046-144) 097 (044-212) 050 (028-088)

P for trend 008 089 00001



Smoking

status



Never 100 100 100 100

Former 246

(140-432)

197

(148-262)

296

(184-476)

199

(088-452)

Current 721

(484-1075)

520

(422-641)

550

(364-832)

321

(158-651)





1-12 618

(398-958)

365

(282-473)

365

(212-628)

290

(115-727)

13-22 792

(501-1253)

639

(498-820)

541

(323-905)

221

(071-686)

23+ 1112

(660-1870)

853

(635-1150)

901

(504-1610)

637

(210-1930)

P trend lt00001 lt00001 lt00001 00001




of lung cancer





damage





weights



developed world



Obesity

Western diet

Physical inactivity

Smoking







GST enzymes







GSTP1 polymorphism







Smokers














us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang













US

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Australia

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Netherlands

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

UK

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female





Solution


men and women


specific data


in Men

0

10

20

30

40

50

60

70

0 10 20 30 40 50 60 70 80 90 100 110 120

0

5

10

15

20

25

30

35

40

of deaths caused by

smoking



male smokers

male deaths

Sub-Saharan Africa

Southeast Asia

China Norway




in Women

0

10

20

30

40

50

60

70

0 10 20 30 40 50 60 70 80 90 100 110 120

0

5

10

15

20

25

30

35

40

of deaths caused by



female smokers

female deaths

Sub-Saharan Africa




Australia

Conclusions










Thank You







Tobacco deaths 2000

Developed 2 million




countries

Tobacco deaths 2030

3 million

7 million




0

10

20

30

40

50

60

70

0 10 20 30 40 50 60 70 80 90 100

0

5

10

15

20

25

30

35

40

of deaths caused by

smoking



19601900 1920 1940 1980 2000

male smokers

female smokers

male deaths

female deaths



through 2005



0

10

20

30

40

50

60

1965

1974

1979

1983

1985

1990

1992

1994

1995

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

2009

2010

Year

Pre

vale

nce (

)



Men

Women

(52)

(34) (215)

(173)


0

10

20

30

40

50

60

70

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Women

0

10

20

30

40

50

60

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Pre

vale

nce


Australia

Men

0

10

20

30

40

50

60

70

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Women

0

10

20

30

40

50

60

70

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Pre

vale

nce




Romania

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Greece

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Poland

0

5

10

15

20

25

30

35

40

45

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Russia

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female



United Kingdom

United States

Canada

New Zealand

Australia







Greece

Italy

Spain





Community Medicine

Faculty of Medicine


March 23 2012


Singapore

Overview




Active smoking risk

Conclusions

Passive smoking

Secondhand smoke

Involuntary smoking











Acrylamide

Acrylonitrile

13-Butadiene

Isoprene

Nitromethane

Propylene Oxide


Vinyl chloride

4-Aminobiphenyl

Urethane

Benzene

Nitrobenzene

Benzo[a]pyrene

ortho-Toluidine

Dibenzo[ae]pyrene

Dibenzo[ai]pyrene

Dibenzo[al]pyrene






Mainstream Smoke

- Carbon monoxide

- Nitrogen Oxides

- Nicotine

25-15 times as much

37-128 times

13-21 as much

- Benzene

- Formaldehyde

- NNK

- Benz(a)pyrene

- Nickel

- Tar

8-10 times as much

50 times as much

1-22 times as much

25-20 times as much

13-30 times as much

11-157 times













01

1

10H

iray

am

a 199

2W

arte

nb

erg

et

al

200

0R

eyn

old

s e

t a

l 20

04

Ha

nao

ka e

t al

200

4S

an

dle

r e

t al 1

985

Millik

an

et

al 1

998

De

lfin

o e

t al

2000

Scru

bso

le e

t al

2004

Gam

mon

et a

l 200

4S

mit

h e

t al

1994

Mo

rab

ia e

t al 1

996

Zh

ao

et

al

1999

Jo

hn

so

n e

t al

200

0K

ro

pp

et

al

200

2L

isso

wsk

a e

t al 2

00

6M

issed

Ex

po

su

re -

Co

ho

rt

Stu

die

s

Mis

sed

Ex

po

su

re -

Cas

e-C

on

tro

l

Be

tte

r E

xp

osu

re

Asses

sm

en

t



|______________________________________|



|_____________________|

Cohort

|___________________________|

Case-control






















cancerrdquo



2005 1

Surgeon Generals

Report 20062


(95 CI)

N Relative Risk

(95 CI)

All studies 19 125 (108-144) 21 120 (108-135)

Premenopausal

Women lt 50

14 168 (131-215) 11 164 (125-214)

Premenopausal

with lifetime

exposure

assessment

5 220 (169-287) 6 185 (119-287)


Balancing Concerns








Ed



0

50

100

150

200

250

USA 1994

Europe 1998

Sweden 1998

Germany 1998

China 1999

Germany 2000

China 2000

Canada 2001

Excess Lung

Cancer Risk

(Percentage)


Higher Exposure

Work Only -

Higher Exposure


+1-25

+35-220 +50-210























Teachers Cohort[48]

Adjusted HR

(95 CI)

Womenrsquos Health


Adjusted HR (95

CI)


exposure

100 100







126 (099-160) 132(104-167)





























Exposure



40+ cigday

138 (105-183)

174 (115-262)



205 (120-349)


gt20 cigday 183 (129-261)


Initiation 10-14 146 (111-193)

148 (103-213)


(premeno) 39 (15-99)


Hanaoka et al 2004



Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)






Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)

Pooled

Analysis

Never

active

100 100 100 100

lt20 105 (086-128) 123 (103-146) 091 (072-116) 110 (089-135)

gt20 149 (108-204) 142 (116-174) 129 (089-186) 088 (069-113)






initiation

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137)

Al-Delaimy(2004) 129 (097-171)

Reynolds (2004) 117 (105-130)

Lawlor (2004)

Gram (2005) 148 (103-213)

Olson (2005) 112 (092-136)

Cui (2006) 111 (097-128)

Ha (2007) 148 (077-284)

8 of 8 positive

4 of 8 Stat Sig




initiation

Longest duration

before pregnancy

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131)

Al-Delaimy(2004) 129 (097-171) 110 (080-152)

Reynolds (2004) 117 (105-130) 113 (100-125)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137)

Olson (2005) 112 (092-136) 121 (101-125)

Cui (2006) 111 (097-128) 113 (101-125)

Ha (2007) 148 (077-284) 178 (127-249)11

9 of 9 positive

4 of 9 Stat Sig




initiation

Longest duration

before pregnancy

Longest

duration

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189)

Ha (2007) 148 (077-284) 178 (127-249)11

6 of 6 positive

3 of 6 Stat Sig




initiation

Longest duration

Before pregnancy

Longest

duration

Highest pack-

years

Calle (1994) 159 (117-215) 138 (105-183)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133) 125 (106-147)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174) 146 (111-193)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138) 115 (096-137)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189) 117 (102-134)

Ha (2007) 148 (077-284) 178 (127-249)11


5 of 5 positive




First Author Year



Relative Risk

(95 CI)

Reynolds et al (2004) lt20 117 (105-130)

Olson et al (2005) lt19 112 (092-136)

Xue et al (2011) lt18 104 (099-111)

Cui et al (2006) lt16 111 (097-128)


Gram et al (2005) lt15 148 (103-213)

Ha et al (2007) lt15 148 (077-284)



















i
























bull History

bull Lung diseases


bull History

bull Lung disease



TOBACCO SMOKE








INFLAMMATION



LUNG CANCER




ndash COPD

ndash Lung cancer









times








bull History

bull Lung disease












bull History

bull Lung diseases

bull COPD









bull Findings






bull Interpretation







Follow up (y)

Po

stb

ron

cho

dila

tor

FEV

1 L

24

25

26

27

28

29

Screen 2 1 2 3 4 5

Sustained Quitters

Continuous Smokers



COPD










bull Asthma

Asthma








32 subjects


10 quit smoking

Lung cancer













200615517-523















Wen et al--2010




Kolappan Gopi--2002

Thank you




Cancer


Lung

Mouth and pharynx

Larynx

Esophagus

Stomach

Pancreas

Liver

Cervix

Bladder

Kidney

Colorectum

Breast




Body mass index






45-74 years







history from women




51 of the cohort




Heavy smokers (12)


Light smokers (88)





Men (n=27292) Women (n=34028)


Percent 422 214 364 913 25 62


Lung cancer


Never 100

1-12 432 (355-523)

13-22 661 (546-802)

23+ 949 (758-1188)

P for trend lt00001

Smoking status

Lung cancer

RR (95 CI)

Never 100

Former 224 (181-278)

Current 585 (499-687)







Body Mass

Index (kgm2)

Never

smokers

Former

smokers

Current

smokers

Adj HR

(95 CI)

Adj HR

(95 CI)

Adj HR

(95 CI)

lt20 100 100 100

20-lt24 102 (071-146) 092 (057-148) 081 (067-099)

24-lt28 072 (046-110) 101 (059-174) 062 (046-082)

28+ 081 (046-144) 097 (044-212) 050 (028-088)

P for trend 008 089 00001



Smoking

status



Never 100 100 100 100

Former 246

(140-432)

197

(148-262)

296

(184-476)

199

(088-452)

Current 721

(484-1075)

520

(422-641)

550

(364-832)

321

(158-651)





1-12 618

(398-958)

365

(282-473)

365

(212-628)

290

(115-727)

13-22 792

(501-1253)

639

(498-820)

541

(323-905)

221

(071-686)

23+ 1112

(660-1870)

853

(635-1150)

901

(504-1610)

637

(210-1930)

P trend lt00001 lt00001 lt00001 00001




of lung cancer





damage





weights



developed world



Obesity

Western diet

Physical inactivity

Smoking







GST enzymes







GSTP1 polymorphism







Smokers














us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang










Solution


men and women


specific data


in Men

0

10

20

30

40

50

60

70

0 10 20 30 40 50 60 70 80 90 100 110 120

0

5

10

15

20

25

30

35

40

of deaths caused by

smoking



male smokers

male deaths

Sub-Saharan Africa

Southeast Asia

China Norway




in Women

0

10

20

30

40

50

60

70

0 10 20 30 40 50 60 70 80 90 100 110 120

0

5

10

15

20

25

30

35

40

of deaths caused by



female smokers

female deaths

Sub-Saharan Africa




Australia

Conclusions










Thank You







Tobacco deaths 2000

Developed 2 million




countries

Tobacco deaths 2030

3 million

7 million




0

10

20

30

40

50

60

70

0 10 20 30 40 50 60 70 80 90 100

0

5

10

15

20

25

30

35

40

of deaths caused by

smoking



19601900 1920 1940 1980 2000

male smokers

female smokers

male deaths

female deaths



through 2005



0

10

20

30

40

50

60

1965

1974

1979

1983

1985

1990

1992

1994

1995

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

2009

2010

Year

Pre

vale

nce (

)



Men

Women

(52)

(34) (215)

(173)


0

10

20

30

40

50

60

70

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Women

0

10

20

30

40

50

60

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Pre

vale

nce


Australia

Men

0

10

20

30

40

50

60

70

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Women

0

10

20

30

40

50

60

70

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Pre

vale

nce




Romania

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Greece

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Poland

0

5

10

15

20

25

30

35

40

45

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Russia

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female



United Kingdom

United States

Canada

New Zealand

Australia







Greece

Italy

Spain





Community Medicine

Faculty of Medicine


March 23 2012


Singapore

Overview




Active smoking risk

Conclusions

Passive smoking

Secondhand smoke

Involuntary smoking











Acrylamide

Acrylonitrile

13-Butadiene

Isoprene

Nitromethane

Propylene Oxide


Vinyl chloride

4-Aminobiphenyl

Urethane

Benzene

Nitrobenzene

Benzo[a]pyrene

ortho-Toluidine

Dibenzo[ae]pyrene

Dibenzo[ai]pyrene

Dibenzo[al]pyrene






Mainstream Smoke

- Carbon monoxide

- Nitrogen Oxides

- Nicotine

25-15 times as much

37-128 times

13-21 as much

- Benzene

- Formaldehyde

- NNK

- Benz(a)pyrene

- Nickel

- Tar

8-10 times as much

50 times as much

1-22 times as much

25-20 times as much

13-30 times as much

11-157 times













01

1

10H

iray

am

a 199

2W

arte

nb

erg

et

al

200

0R

eyn

old

s e

t a

l 20

04

Ha

nao

ka e

t al

200

4S

an

dle

r e

t al 1

985

Millik

an

et

al 1

998

De

lfin

o e

t al

2000

Scru

bso

le e

t al

2004

Gam

mon

et a

l 200

4S

mit

h e

t al

1994

Mo

rab

ia e

t al 1

996

Zh

ao

et

al

1999

Jo

hn

so

n e

t al

200

0K

ro

pp

et

al

200

2L

isso

wsk

a e

t al 2

00

6M

issed

Ex

po

su

re -

Co

ho

rt

Stu

die

s

Mis

sed

Ex

po

su

re -

Cas

e-C

on

tro

l

Be

tte

r E

xp

osu

re

Asses

sm

en

t



|______________________________________|



|_____________________|

Cohort

|___________________________|

Case-control






















cancerrdquo



2005 1

Surgeon Generals

Report 20062


(95 CI)

N Relative Risk

(95 CI)

All studies 19 125 (108-144) 21 120 (108-135)

Premenopausal

Women lt 50

14 168 (131-215) 11 164 (125-214)

Premenopausal

with lifetime

exposure

assessment

5 220 (169-287) 6 185 (119-287)


Balancing Concerns








Ed



0

50

100

150

200

250

USA 1994

Europe 1998

Sweden 1998

Germany 1998

China 1999

Germany 2000

China 2000

Canada 2001

Excess Lung

Cancer Risk

(Percentage)


Higher Exposure

Work Only -

Higher Exposure


+1-25

+35-220 +50-210























Teachers Cohort[48]

Adjusted HR

(95 CI)

Womenrsquos Health


Adjusted HR (95

CI)


exposure

100 100







126 (099-160) 132(104-167)





























Exposure



40+ cigday

138 (105-183)

174 (115-262)



205 (120-349)


gt20 cigday 183 (129-261)


Initiation 10-14 146 (111-193)

148 (103-213)


(premeno) 39 (15-99)


Hanaoka et al 2004



Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)






Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)

Pooled

Analysis

Never

active

100 100 100 100

lt20 105 (086-128) 123 (103-146) 091 (072-116) 110 (089-135)

gt20 149 (108-204) 142 (116-174) 129 (089-186) 088 (069-113)






initiation

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137)

Al-Delaimy(2004) 129 (097-171)

Reynolds (2004) 117 (105-130)

Lawlor (2004)

Gram (2005) 148 (103-213)

Olson (2005) 112 (092-136)

Cui (2006) 111 (097-128)

Ha (2007) 148 (077-284)

8 of 8 positive

4 of 8 Stat Sig




initiation

Longest duration

before pregnancy

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131)

Al-Delaimy(2004) 129 (097-171) 110 (080-152)

Reynolds (2004) 117 (105-130) 113 (100-125)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137)

Olson (2005) 112 (092-136) 121 (101-125)

Cui (2006) 111 (097-128) 113 (101-125)

Ha (2007) 148 (077-284) 178 (127-249)11

9 of 9 positive

4 of 9 Stat Sig




initiation

Longest duration

before pregnancy

Longest

duration

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189)

Ha (2007) 148 (077-284) 178 (127-249)11

6 of 6 positive

3 of 6 Stat Sig




initiation

Longest duration

Before pregnancy

Longest

duration

Highest pack-

years

Calle (1994) 159 (117-215) 138 (105-183)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133) 125 (106-147)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174) 146 (111-193)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138) 115 (096-137)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189) 117 (102-134)

Ha (2007) 148 (077-284) 178 (127-249)11


5 of 5 positive




First Author Year



Relative Risk

(95 CI)

Reynolds et al (2004) lt20 117 (105-130)

Olson et al (2005) lt19 112 (092-136)

Xue et al (2011) lt18 104 (099-111)

Cui et al (2006) lt16 111 (097-128)


Gram et al (2005) lt15 148 (103-213)

Ha et al (2007) lt15 148 (077-284)



















i
























bull History

bull Lung diseases


bull History

bull Lung disease



TOBACCO SMOKE








INFLAMMATION



LUNG CANCER




ndash COPD

ndash Lung cancer









times








bull History

bull Lung disease












bull History

bull Lung diseases

bull COPD









bull Findings






bull Interpretation







Follow up (y)

Po

stb

ron

cho

dila

tor

FEV

1 L

24

25

26

27

28

29

Screen 2 1 2 3 4 5

Sustained Quitters

Continuous Smokers



COPD










bull Asthma

Asthma








32 subjects


10 quit smoking

Lung cancer













200615517-523















Wen et al--2010




Kolappan Gopi--2002

Thank you




Cancer


Lung

Mouth and pharynx

Larynx

Esophagus

Stomach

Pancreas

Liver

Cervix

Bladder

Kidney

Colorectum

Breast




Body mass index






45-74 years







history from women




51 of the cohort




Heavy smokers (12)


Light smokers (88)





Men (n=27292) Women (n=34028)


Percent 422 214 364 913 25 62


Lung cancer


Never 100

1-12 432 (355-523)

13-22 661 (546-802)

23+ 949 (758-1188)

P for trend lt00001

Smoking status

Lung cancer

RR (95 CI)

Never 100

Former 224 (181-278)

Current 585 (499-687)







Body Mass

Index (kgm2)

Never

smokers

Former

smokers

Current

smokers

Adj HR

(95 CI)

Adj HR

(95 CI)

Adj HR

(95 CI)

lt20 100 100 100

20-lt24 102 (071-146) 092 (057-148) 081 (067-099)

24-lt28 072 (046-110) 101 (059-174) 062 (046-082)

28+ 081 (046-144) 097 (044-212) 050 (028-088)

P for trend 008 089 00001



Smoking

status



Never 100 100 100 100

Former 246

(140-432)

197

(148-262)

296

(184-476)

199

(088-452)

Current 721

(484-1075)

520

(422-641)

550

(364-832)

321

(158-651)





1-12 618

(398-958)

365

(282-473)

365

(212-628)

290

(115-727)

13-22 792

(501-1253)

639

(498-820)

541

(323-905)

221

(071-686)

23+ 1112

(660-1870)

853

(635-1150)

901

(504-1610)

637

(210-1930)

P trend lt00001 lt00001 lt00001 00001




of lung cancer





damage





weights



developed world



Obesity

Western diet

Physical inactivity

Smoking







GST enzymes







GSTP1 polymorphism







Smokers














us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang








in Men

0

10

20

30

40

50

60

70

0 10 20 30 40 50 60 70 80 90 100 110 120

0

5

10

15

20

25

30

35

40

of deaths caused by

smoking



male smokers

male deaths

Sub-Saharan Africa

Southeast Asia

China Norway




in Women

0

10

20

30

40

50

60

70

0 10 20 30 40 50 60 70 80 90 100 110 120

0

5

10

15

20

25

30

35

40

of deaths caused by



female smokers

female deaths

Sub-Saharan Africa




Australia

Conclusions










Thank You







Tobacco deaths 2000

Developed 2 million




countries

Tobacco deaths 2030

3 million

7 million




0

10

20

30

40

50

60

70

0 10 20 30 40 50 60 70 80 90 100

0

5

10

15

20

25

30

35

40

of deaths caused by

smoking



19601900 1920 1940 1980 2000

male smokers

female smokers

male deaths

female deaths



through 2005



0

10

20

30

40

50

60

1965

1974

1979

1983

1985

1990

1992

1994

1995

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

2009

2010

Year

Pre

vale

nce (

)



Men

Women

(52)

(34) (215)

(173)


0

10

20

30

40

50

60

70

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Women

0

10

20

30

40

50

60

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Pre

vale

nce


Australia

Men

0

10

20

30

40

50

60

70

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Women

0

10

20

30

40

50

60

70

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Pre

vale

nce




Romania

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Greece

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Poland

0

5

10

15

20

25

30

35

40

45

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Russia

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female



United Kingdom

United States

Canada

New Zealand

Australia







Greece

Italy

Spain





Community Medicine

Faculty of Medicine


March 23 2012


Singapore

Overview




Active smoking risk

Conclusions

Passive smoking

Secondhand smoke

Involuntary smoking











Acrylamide

Acrylonitrile

13-Butadiene

Isoprene

Nitromethane

Propylene Oxide


Vinyl chloride

4-Aminobiphenyl

Urethane

Benzene

Nitrobenzene

Benzo[a]pyrene

ortho-Toluidine

Dibenzo[ae]pyrene

Dibenzo[ai]pyrene

Dibenzo[al]pyrene






Mainstream Smoke

- Carbon monoxide

- Nitrogen Oxides

- Nicotine

25-15 times as much

37-128 times

13-21 as much

- Benzene

- Formaldehyde

- NNK

- Benz(a)pyrene

- Nickel

- Tar

8-10 times as much

50 times as much

1-22 times as much

25-20 times as much

13-30 times as much

11-157 times













01

1

10H

iray

am

a 199

2W

arte

nb

erg

et

al

200

0R

eyn

old

s e

t a

l 20

04

Ha

nao

ka e

t al

200

4S

an

dle

r e

t al 1

985

Millik

an

et

al 1

998

De

lfin

o e

t al

2000

Scru

bso

le e

t al

2004

Gam

mon

et a

l 200

4S

mit

h e

t al

1994

Mo

rab

ia e

t al 1

996

Zh

ao

et

al

1999

Jo

hn

so

n e

t al

200

0K

ro

pp

et

al

200

2L

isso

wsk

a e

t al 2

00

6M

issed

Ex

po

su

re -

Co

ho

rt

Stu

die

s

Mis

sed

Ex

po

su

re -

Cas

e-C

on

tro

l

Be

tte

r E

xp

osu

re

Asses

sm

en

t



|______________________________________|



|_____________________|

Cohort

|___________________________|

Case-control






















cancerrdquo



2005 1

Surgeon Generals

Report 20062


(95 CI)

N Relative Risk

(95 CI)

All studies 19 125 (108-144) 21 120 (108-135)

Premenopausal

Women lt 50

14 168 (131-215) 11 164 (125-214)

Premenopausal

with lifetime

exposure

assessment

5 220 (169-287) 6 185 (119-287)


Balancing Concerns








Ed



0

50

100

150

200

250

USA 1994

Europe 1998

Sweden 1998

Germany 1998

China 1999

Germany 2000

China 2000

Canada 2001

Excess Lung

Cancer Risk

(Percentage)


Higher Exposure

Work Only -

Higher Exposure


+1-25

+35-220 +50-210























Teachers Cohort[48]

Adjusted HR

(95 CI)

Womenrsquos Health


Adjusted HR (95

CI)


exposure

100 100







126 (099-160) 132(104-167)





























Exposure



40+ cigday

138 (105-183)

174 (115-262)



205 (120-349)


gt20 cigday 183 (129-261)


Initiation 10-14 146 (111-193)

148 (103-213)


(premeno) 39 (15-99)


Hanaoka et al 2004



Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)






Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)

Pooled

Analysis

Never

active

100 100 100 100

lt20 105 (086-128) 123 (103-146) 091 (072-116) 110 (089-135)

gt20 149 (108-204) 142 (116-174) 129 (089-186) 088 (069-113)






initiation

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137)

Al-Delaimy(2004) 129 (097-171)

Reynolds (2004) 117 (105-130)

Lawlor (2004)

Gram (2005) 148 (103-213)

Olson (2005) 112 (092-136)

Cui (2006) 111 (097-128)

Ha (2007) 148 (077-284)

8 of 8 positive

4 of 8 Stat Sig




initiation

Longest duration

before pregnancy

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131)

Al-Delaimy(2004) 129 (097-171) 110 (080-152)

Reynolds (2004) 117 (105-130) 113 (100-125)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137)

Olson (2005) 112 (092-136) 121 (101-125)

Cui (2006) 111 (097-128) 113 (101-125)

Ha (2007) 148 (077-284) 178 (127-249)11

9 of 9 positive

4 of 9 Stat Sig




initiation

Longest duration

before pregnancy

Longest

duration

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189)

Ha (2007) 148 (077-284) 178 (127-249)11

6 of 6 positive

3 of 6 Stat Sig




initiation

Longest duration

Before pregnancy

Longest

duration

Highest pack-

years

Calle (1994) 159 (117-215) 138 (105-183)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133) 125 (106-147)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174) 146 (111-193)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138) 115 (096-137)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189) 117 (102-134)

Ha (2007) 148 (077-284) 178 (127-249)11


5 of 5 positive




First Author Year



Relative Risk

(95 CI)

Reynolds et al (2004) lt20 117 (105-130)

Olson et al (2005) lt19 112 (092-136)

Xue et al (2011) lt18 104 (099-111)

Cui et al (2006) lt16 111 (097-128)


Gram et al (2005) lt15 148 (103-213)

Ha et al (2007) lt15 148 (077-284)



















i
























bull History

bull Lung diseases


bull History

bull Lung disease



TOBACCO SMOKE








INFLAMMATION



LUNG CANCER




ndash COPD

ndash Lung cancer









times








bull History

bull Lung disease












bull History

bull Lung diseases

bull COPD









bull Findings






bull Interpretation







Follow up (y)

Po

stb

ron

cho

dila

tor

FEV

1 L

24

25

26

27

28

29

Screen 2 1 2 3 4 5

Sustained Quitters

Continuous Smokers



COPD










bull Asthma

Asthma








32 subjects


10 quit smoking

Lung cancer













200615517-523















Wen et al--2010




Kolappan Gopi--2002

Thank you




Cancer


Lung

Mouth and pharynx

Larynx

Esophagus

Stomach

Pancreas

Liver

Cervix

Bladder

Kidney

Colorectum

Breast




Body mass index






45-74 years







history from women




51 of the cohort




Heavy smokers (12)


Light smokers (88)





Men (n=27292) Women (n=34028)


Percent 422 214 364 913 25 62


Lung cancer


Never 100

1-12 432 (355-523)

13-22 661 (546-802)

23+ 949 (758-1188)

P for trend lt00001

Smoking status

Lung cancer

RR (95 CI)

Never 100

Former 224 (181-278)

Current 585 (499-687)







Body Mass

Index (kgm2)

Never

smokers

Former

smokers

Current

smokers

Adj HR

(95 CI)

Adj HR

(95 CI)

Adj HR

(95 CI)

lt20 100 100 100

20-lt24 102 (071-146) 092 (057-148) 081 (067-099)

24-lt28 072 (046-110) 101 (059-174) 062 (046-082)

28+ 081 (046-144) 097 (044-212) 050 (028-088)

P for trend 008 089 00001



Smoking

status



Never 100 100 100 100

Former 246

(140-432)

197

(148-262)

296

(184-476)

199

(088-452)

Current 721

(484-1075)

520

(422-641)

550

(364-832)

321

(158-651)





1-12 618

(398-958)

365

(282-473)

365

(212-628)

290

(115-727)

13-22 792

(501-1253)

639

(498-820)

541

(323-905)

221

(071-686)

23+ 1112

(660-1870)

853

(635-1150)

901

(504-1610)

637

(210-1930)

P trend lt00001 lt00001 lt00001 00001




of lung cancer





damage





weights



developed world



Obesity

Western diet

Physical inactivity

Smoking







GST enzymes







GSTP1 polymorphism







Smokers














us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang








in Women

0

10

20

30

40

50

60

70

0 10 20 30 40 50 60 70 80 90 100 110 120

0

5

10

15

20

25

30

35

40

of deaths caused by



female smokers

female deaths

Sub-Saharan Africa




Australia

Conclusions










Thank You







Tobacco deaths 2000

Developed 2 million




countries

Tobacco deaths 2030

3 million

7 million




0

10

20

30

40

50

60

70

0 10 20 30 40 50 60 70 80 90 100

0

5

10

15

20

25

30

35

40

of deaths caused by

smoking



19601900 1920 1940 1980 2000

male smokers

female smokers

male deaths

female deaths



through 2005



0

10

20

30

40

50

60

1965

1974

1979

1983

1985

1990

1992

1994

1995

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

2009

2010

Year

Pre

vale

nce (

)



Men

Women

(52)

(34) (215)

(173)


0

10

20

30

40

50

60

70

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Women

0

10

20

30

40

50

60

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Pre

vale

nce


Australia

Men

0

10

20

30

40

50

60

70

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Women

0

10

20

30

40

50

60

70

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Pre

vale

nce




Romania

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Greece

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Poland

0

5

10

15

20

25

30

35

40

45

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Russia

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female



United Kingdom

United States

Canada

New Zealand

Australia







Greece

Italy

Spain





Community Medicine

Faculty of Medicine


March 23 2012


Singapore

Overview




Active smoking risk

Conclusions

Passive smoking

Secondhand smoke

Involuntary smoking











Acrylamide

Acrylonitrile

13-Butadiene

Isoprene

Nitromethane

Propylene Oxide


Vinyl chloride

4-Aminobiphenyl

Urethane

Benzene

Nitrobenzene

Benzo[a]pyrene

ortho-Toluidine

Dibenzo[ae]pyrene

Dibenzo[ai]pyrene

Dibenzo[al]pyrene






Mainstream Smoke

- Carbon monoxide

- Nitrogen Oxides

- Nicotine

25-15 times as much

37-128 times

13-21 as much

- Benzene

- Formaldehyde

- NNK

- Benz(a)pyrene

- Nickel

- Tar

8-10 times as much

50 times as much

1-22 times as much

25-20 times as much

13-30 times as much

11-157 times













01

1

10H

iray

am

a 199

2W

arte

nb

erg

et

al

200

0R

eyn

old

s e

t a

l 20

04

Ha

nao

ka e

t al

200

4S

an

dle

r e

t al 1

985

Millik

an

et

al 1

998

De

lfin

o e

t al

2000

Scru

bso

le e

t al

2004

Gam

mon

et a

l 200

4S

mit

h e

t al

1994

Mo

rab

ia e

t al 1

996

Zh

ao

et

al

1999

Jo

hn

so

n e

t al

200

0K

ro

pp

et

al

200

2L

isso

wsk

a e

t al 2

00

6M

issed

Ex

po

su

re -

Co

ho

rt

Stu

die

s

Mis

sed

Ex

po

su

re -

Cas

e-C

on

tro

l

Be

tte

r E

xp

osu

re

Asses

sm

en

t



|______________________________________|



|_____________________|

Cohort

|___________________________|

Case-control






















cancerrdquo



2005 1

Surgeon Generals

Report 20062


(95 CI)

N Relative Risk

(95 CI)

All studies 19 125 (108-144) 21 120 (108-135)

Premenopausal

Women lt 50

14 168 (131-215) 11 164 (125-214)

Premenopausal

with lifetime

exposure

assessment

5 220 (169-287) 6 185 (119-287)


Balancing Concerns








Ed



0

50

100

150

200

250

USA 1994

Europe 1998

Sweden 1998

Germany 1998

China 1999

Germany 2000

China 2000

Canada 2001

Excess Lung

Cancer Risk

(Percentage)


Higher Exposure

Work Only -

Higher Exposure


+1-25

+35-220 +50-210























Teachers Cohort[48]

Adjusted HR

(95 CI)

Womenrsquos Health


Adjusted HR (95

CI)


exposure

100 100







126 (099-160) 132(104-167)





























Exposure



40+ cigday

138 (105-183)

174 (115-262)



205 (120-349)


gt20 cigday 183 (129-261)


Initiation 10-14 146 (111-193)

148 (103-213)


(premeno) 39 (15-99)


Hanaoka et al 2004



Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)






Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)

Pooled

Analysis

Never

active

100 100 100 100

lt20 105 (086-128) 123 (103-146) 091 (072-116) 110 (089-135)

gt20 149 (108-204) 142 (116-174) 129 (089-186) 088 (069-113)






initiation

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137)

Al-Delaimy(2004) 129 (097-171)

Reynolds (2004) 117 (105-130)

Lawlor (2004)

Gram (2005) 148 (103-213)

Olson (2005) 112 (092-136)

Cui (2006) 111 (097-128)

Ha (2007) 148 (077-284)

8 of 8 positive

4 of 8 Stat Sig




initiation

Longest duration

before pregnancy

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131)

Al-Delaimy(2004) 129 (097-171) 110 (080-152)

Reynolds (2004) 117 (105-130) 113 (100-125)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137)

Olson (2005) 112 (092-136) 121 (101-125)

Cui (2006) 111 (097-128) 113 (101-125)

Ha (2007) 148 (077-284) 178 (127-249)11

9 of 9 positive

4 of 9 Stat Sig




initiation

Longest duration

before pregnancy

Longest

duration

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189)

Ha (2007) 148 (077-284) 178 (127-249)11

6 of 6 positive

3 of 6 Stat Sig




initiation

Longest duration

Before pregnancy

Longest

duration

Highest pack-

years

Calle (1994) 159 (117-215) 138 (105-183)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133) 125 (106-147)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174) 146 (111-193)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138) 115 (096-137)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189) 117 (102-134)

Ha (2007) 148 (077-284) 178 (127-249)11


5 of 5 positive




First Author Year



Relative Risk

(95 CI)

Reynolds et al (2004) lt20 117 (105-130)

Olson et al (2005) lt19 112 (092-136)

Xue et al (2011) lt18 104 (099-111)

Cui et al (2006) lt16 111 (097-128)


Gram et al (2005) lt15 148 (103-213)

Ha et al (2007) lt15 148 (077-284)



















i
























bull History

bull Lung diseases


bull History

bull Lung disease



TOBACCO SMOKE








INFLAMMATION



LUNG CANCER




ndash COPD

ndash Lung cancer









times








bull History

bull Lung disease












bull History

bull Lung diseases

bull COPD









bull Findings






bull Interpretation







Follow up (y)

Po

stb

ron

cho

dila

tor

FEV

1 L

24

25

26

27

28

29

Screen 2 1 2 3 4 5

Sustained Quitters

Continuous Smokers



COPD










bull Asthma

Asthma








32 subjects


10 quit smoking

Lung cancer













200615517-523















Wen et al--2010




Kolappan Gopi--2002

Thank you




Cancer


Lung

Mouth and pharynx

Larynx

Esophagus

Stomach

Pancreas

Liver

Cervix

Bladder

Kidney

Colorectum

Breast




Body mass index






45-74 years







history from women




51 of the cohort




Heavy smokers (12)


Light smokers (88)





Men (n=27292) Women (n=34028)


Percent 422 214 364 913 25 62


Lung cancer


Never 100

1-12 432 (355-523)

13-22 661 (546-802)

23+ 949 (758-1188)

P for trend lt00001

Smoking status

Lung cancer

RR (95 CI)

Never 100

Former 224 (181-278)

Current 585 (499-687)







Body Mass

Index (kgm2)

Never

smokers

Former

smokers

Current

smokers

Adj HR

(95 CI)

Adj HR

(95 CI)

Adj HR

(95 CI)

lt20 100 100 100

20-lt24 102 (071-146) 092 (057-148) 081 (067-099)

24-lt28 072 (046-110) 101 (059-174) 062 (046-082)

28+ 081 (046-144) 097 (044-212) 050 (028-088)

P for trend 008 089 00001



Smoking

status



Never 100 100 100 100

Former 246

(140-432)

197

(148-262)

296

(184-476)

199

(088-452)

Current 721

(484-1075)

520

(422-641)

550

(364-832)

321

(158-651)





1-12 618

(398-958)

365

(282-473)

365

(212-628)

290

(115-727)

13-22 792

(501-1253)

639

(498-820)

541

(323-905)

221

(071-686)

23+ 1112

(660-1870)

853

(635-1150)

901

(504-1610)

637

(210-1930)

P trend lt00001 lt00001 lt00001 00001




of lung cancer





damage





weights



developed world



Obesity

Western diet

Physical inactivity

Smoking







GST enzymes







GSTP1 polymorphism







Smokers














us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang







Conclusions










Thank You







Tobacco deaths 2000

Developed 2 million




countries

Tobacco deaths 2030

3 million

7 million




0

10

20

30

40

50

60

70

0 10 20 30 40 50 60 70 80 90 100

0

5

10

15

20

25

30

35

40

of deaths caused by

smoking



19601900 1920 1940 1980 2000

male smokers

female smokers

male deaths

female deaths



through 2005



0

10

20

30

40

50

60

1965

1974

1979

1983

1985

1990

1992

1994

1995

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

2009

2010

Year

Pre

vale

nce (

)



Men

Women

(52)

(34) (215)

(173)


0

10

20

30

40

50

60

70

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Women

0

10

20

30

40

50

60

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Pre

vale

nce


Australia

Men

0

10

20

30

40

50

60

70

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Women

0

10

20

30

40

50

60

70

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Pre

vale

nce




Romania

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Greece

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Poland

0

5

10

15

20

25

30

35

40

45

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Russia

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female



United Kingdom

United States

Canada

New Zealand

Australia







Greece

Italy

Spain





Community Medicine

Faculty of Medicine


March 23 2012


Singapore

Overview




Active smoking risk

Conclusions

Passive smoking

Secondhand smoke

Involuntary smoking











Acrylamide

Acrylonitrile

13-Butadiene

Isoprene

Nitromethane

Propylene Oxide


Vinyl chloride

4-Aminobiphenyl

Urethane

Benzene

Nitrobenzene

Benzo[a]pyrene

ortho-Toluidine

Dibenzo[ae]pyrene

Dibenzo[ai]pyrene

Dibenzo[al]pyrene






Mainstream Smoke

- Carbon monoxide

- Nitrogen Oxides

- Nicotine

25-15 times as much

37-128 times

13-21 as much

- Benzene

- Formaldehyde

- NNK

- Benz(a)pyrene

- Nickel

- Tar

8-10 times as much

50 times as much

1-22 times as much

25-20 times as much

13-30 times as much

11-157 times













01

1

10H

iray

am

a 199

2W

arte

nb

erg

et

al

200

0R

eyn

old

s e

t a

l 20

04

Ha

nao

ka e

t al

200

4S

an

dle

r e

t al 1

985

Millik

an

et

al 1

998

De

lfin

o e

t al

2000

Scru

bso

le e

t al

2004

Gam

mon

et a

l 200

4S

mit

h e

t al

1994

Mo

rab

ia e

t al 1

996

Zh

ao

et

al

1999

Jo

hn

so

n e

t al

200

0K

ro

pp

et

al

200

2L

isso

wsk

a e

t al 2

00

6M

issed

Ex

po

su

re -

Co

ho

rt

Stu

die

s

Mis

sed

Ex

po

su

re -

Cas

e-C

on

tro

l

Be

tte

r E

xp

osu

re

Asses

sm

en

t



|______________________________________|



|_____________________|

Cohort

|___________________________|

Case-control






















cancerrdquo



2005 1

Surgeon Generals

Report 20062


(95 CI)

N Relative Risk

(95 CI)

All studies 19 125 (108-144) 21 120 (108-135)

Premenopausal

Women lt 50

14 168 (131-215) 11 164 (125-214)

Premenopausal

with lifetime

exposure

assessment

5 220 (169-287) 6 185 (119-287)


Balancing Concerns








Ed



0

50

100

150

200

250

USA 1994

Europe 1998

Sweden 1998

Germany 1998

China 1999

Germany 2000

China 2000

Canada 2001

Excess Lung

Cancer Risk

(Percentage)


Higher Exposure

Work Only -

Higher Exposure


+1-25

+35-220 +50-210























Teachers Cohort[48]

Adjusted HR

(95 CI)

Womenrsquos Health


Adjusted HR (95

CI)


exposure

100 100







126 (099-160) 132(104-167)





























Exposure



40+ cigday

138 (105-183)

174 (115-262)



205 (120-349)


gt20 cigday 183 (129-261)


Initiation 10-14 146 (111-193)

148 (103-213)


(premeno) 39 (15-99)


Hanaoka et al 2004



Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)






Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)

Pooled

Analysis

Never

active

100 100 100 100

lt20 105 (086-128) 123 (103-146) 091 (072-116) 110 (089-135)

gt20 149 (108-204) 142 (116-174) 129 (089-186) 088 (069-113)






initiation

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137)

Al-Delaimy(2004) 129 (097-171)

Reynolds (2004) 117 (105-130)

Lawlor (2004)

Gram (2005) 148 (103-213)

Olson (2005) 112 (092-136)

Cui (2006) 111 (097-128)

Ha (2007) 148 (077-284)

8 of 8 positive

4 of 8 Stat Sig




initiation

Longest duration

before pregnancy

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131)

Al-Delaimy(2004) 129 (097-171) 110 (080-152)

Reynolds (2004) 117 (105-130) 113 (100-125)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137)

Olson (2005) 112 (092-136) 121 (101-125)

Cui (2006) 111 (097-128) 113 (101-125)

Ha (2007) 148 (077-284) 178 (127-249)11

9 of 9 positive

4 of 9 Stat Sig




initiation

Longest duration

before pregnancy

Longest

duration

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189)

Ha (2007) 148 (077-284) 178 (127-249)11

6 of 6 positive

3 of 6 Stat Sig




initiation

Longest duration

Before pregnancy

Longest

duration

Highest pack-

years

Calle (1994) 159 (117-215) 138 (105-183)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133) 125 (106-147)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174) 146 (111-193)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138) 115 (096-137)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189) 117 (102-134)

Ha (2007) 148 (077-284) 178 (127-249)11


5 of 5 positive




First Author Year



Relative Risk

(95 CI)

Reynolds et al (2004) lt20 117 (105-130)

Olson et al (2005) lt19 112 (092-136)

Xue et al (2011) lt18 104 (099-111)

Cui et al (2006) lt16 111 (097-128)


Gram et al (2005) lt15 148 (103-213)

Ha et al (2007) lt15 148 (077-284)



















i
























bull History

bull Lung diseases


bull History

bull Lung disease



TOBACCO SMOKE








INFLAMMATION



LUNG CANCER




ndash COPD

ndash Lung cancer









times








bull History

bull Lung disease












bull History

bull Lung diseases

bull COPD









bull Findings






bull Interpretation







Follow up (y)

Po

stb

ron

cho

dila

tor

FEV

1 L

24

25

26

27

28

29

Screen 2 1 2 3 4 5

Sustained Quitters

Continuous Smokers



COPD










bull Asthma

Asthma








32 subjects


10 quit smoking

Lung cancer













200615517-523















Wen et al--2010




Kolappan Gopi--2002

Thank you




Cancer


Lung

Mouth and pharynx

Larynx

Esophagus

Stomach

Pancreas

Liver

Cervix

Bladder

Kidney

Colorectum

Breast




Body mass index






45-74 years







history from women




51 of the cohort




Heavy smokers (12)


Light smokers (88)





Men (n=27292) Women (n=34028)


Percent 422 214 364 913 25 62


Lung cancer


Never 100

1-12 432 (355-523)

13-22 661 (546-802)

23+ 949 (758-1188)

P for trend lt00001

Smoking status

Lung cancer

RR (95 CI)

Never 100

Former 224 (181-278)

Current 585 (499-687)







Body Mass

Index (kgm2)

Never

smokers

Former

smokers

Current

smokers

Adj HR

(95 CI)

Adj HR

(95 CI)

Adj HR

(95 CI)

lt20 100 100 100

20-lt24 102 (071-146) 092 (057-148) 081 (067-099)

24-lt28 072 (046-110) 101 (059-174) 062 (046-082)

28+ 081 (046-144) 097 (044-212) 050 (028-088)

P for trend 008 089 00001



Smoking

status



Never 100 100 100 100

Former 246

(140-432)

197

(148-262)

296

(184-476)

199

(088-452)

Current 721

(484-1075)

520

(422-641)

550

(364-832)

321

(158-651)





1-12 618

(398-958)

365

(282-473)

365

(212-628)

290

(115-727)

13-22 792

(501-1253)

639

(498-820)

541

(323-905)

221

(071-686)

23+ 1112

(660-1870)

853

(635-1150)

901

(504-1610)

637

(210-1930)

P trend lt00001 lt00001 lt00001 00001




of lung cancer





damage





weights



developed world



Obesity

Western diet

Physical inactivity

Smoking







GST enzymes







GSTP1 polymorphism







Smokers














us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang







Thank You







Tobacco deaths 2000

Developed 2 million




countries

Tobacco deaths 2030

3 million

7 million




0

10

20

30

40

50

60

70

0 10 20 30 40 50 60 70 80 90 100

0

5

10

15

20

25

30

35

40

of deaths caused by

smoking



19601900 1920 1940 1980 2000

male smokers

female smokers

male deaths

female deaths



through 2005



0

10

20

30

40

50

60

1965

1974

1979

1983

1985

1990

1992

1994

1995

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

2009

2010

Year

Pre

vale

nce (

)



Men

Women

(52)

(34) (215)

(173)


0

10

20

30

40

50

60

70

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Women

0

10

20

30

40

50

60

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Pre

vale

nce


Australia

Men

0

10

20

30

40

50

60

70

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Women

0

10

20

30

40

50

60

70

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Pre

vale

nce




Romania

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Greece

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Poland

0

5

10

15

20

25

30

35

40

45

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Russia

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female



United Kingdom

United States

Canada

New Zealand

Australia







Greece

Italy

Spain





Community Medicine

Faculty of Medicine


March 23 2012


Singapore

Overview




Active smoking risk

Conclusions

Passive smoking

Secondhand smoke

Involuntary smoking











Acrylamide

Acrylonitrile

13-Butadiene

Isoprene

Nitromethane

Propylene Oxide


Vinyl chloride

4-Aminobiphenyl

Urethane

Benzene

Nitrobenzene

Benzo[a]pyrene

ortho-Toluidine

Dibenzo[ae]pyrene

Dibenzo[ai]pyrene

Dibenzo[al]pyrene






Mainstream Smoke

- Carbon monoxide

- Nitrogen Oxides

- Nicotine

25-15 times as much

37-128 times

13-21 as much

- Benzene

- Formaldehyde

- NNK

- Benz(a)pyrene

- Nickel

- Tar

8-10 times as much

50 times as much

1-22 times as much

25-20 times as much

13-30 times as much

11-157 times













01

1

10H

iray

am

a 199

2W

arte

nb

erg

et

al

200

0R

eyn

old

s e

t a

l 20

04

Ha

nao

ka e

t al

200

4S

an

dle

r e

t al 1

985

Millik

an

et

al 1

998

De

lfin

o e

t al

2000

Scru

bso

le e

t al

2004

Gam

mon

et a

l 200

4S

mit

h e

t al

1994

Mo

rab

ia e

t al 1

996

Zh

ao

et

al

1999

Jo

hn

so

n e

t al

200

0K

ro

pp

et

al

200

2L

isso

wsk

a e

t al 2

00

6M

issed

Ex

po

su

re -

Co

ho

rt

Stu

die

s

Mis

sed

Ex

po

su

re -

Cas

e-C

on

tro

l

Be

tte

r E

xp

osu

re

Asses

sm

en

t



|______________________________________|



|_____________________|

Cohort

|___________________________|

Case-control






















cancerrdquo



2005 1

Surgeon Generals

Report 20062


(95 CI)

N Relative Risk

(95 CI)

All studies 19 125 (108-144) 21 120 (108-135)

Premenopausal

Women lt 50

14 168 (131-215) 11 164 (125-214)

Premenopausal

with lifetime

exposure

assessment

5 220 (169-287) 6 185 (119-287)


Balancing Concerns








Ed



0

50

100

150

200

250

USA 1994

Europe 1998

Sweden 1998

Germany 1998

China 1999

Germany 2000

China 2000

Canada 2001

Excess Lung

Cancer Risk

(Percentage)


Higher Exposure

Work Only -

Higher Exposure


+1-25

+35-220 +50-210























Teachers Cohort[48]

Adjusted HR

(95 CI)

Womenrsquos Health


Adjusted HR (95

CI)


exposure

100 100







126 (099-160) 132(104-167)





























Exposure



40+ cigday

138 (105-183)

174 (115-262)



205 (120-349)


gt20 cigday 183 (129-261)


Initiation 10-14 146 (111-193)

148 (103-213)


(premeno) 39 (15-99)


Hanaoka et al 2004



Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)






Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)

Pooled

Analysis

Never

active

100 100 100 100

lt20 105 (086-128) 123 (103-146) 091 (072-116) 110 (089-135)

gt20 149 (108-204) 142 (116-174) 129 (089-186) 088 (069-113)






initiation

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137)

Al-Delaimy(2004) 129 (097-171)

Reynolds (2004) 117 (105-130)

Lawlor (2004)

Gram (2005) 148 (103-213)

Olson (2005) 112 (092-136)

Cui (2006) 111 (097-128)

Ha (2007) 148 (077-284)

8 of 8 positive

4 of 8 Stat Sig




initiation

Longest duration

before pregnancy

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131)

Al-Delaimy(2004) 129 (097-171) 110 (080-152)

Reynolds (2004) 117 (105-130) 113 (100-125)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137)

Olson (2005) 112 (092-136) 121 (101-125)

Cui (2006) 111 (097-128) 113 (101-125)

Ha (2007) 148 (077-284) 178 (127-249)11

9 of 9 positive

4 of 9 Stat Sig




initiation

Longest duration

before pregnancy

Longest

duration

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189)

Ha (2007) 148 (077-284) 178 (127-249)11

6 of 6 positive

3 of 6 Stat Sig




initiation

Longest duration

Before pregnancy

Longest

duration

Highest pack-

years

Calle (1994) 159 (117-215) 138 (105-183)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133) 125 (106-147)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174) 146 (111-193)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138) 115 (096-137)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189) 117 (102-134)

Ha (2007) 148 (077-284) 178 (127-249)11


5 of 5 positive




First Author Year



Relative Risk

(95 CI)

Reynolds et al (2004) lt20 117 (105-130)

Olson et al (2005) lt19 112 (092-136)

Xue et al (2011) lt18 104 (099-111)

Cui et al (2006) lt16 111 (097-128)


Gram et al (2005) lt15 148 (103-213)

Ha et al (2007) lt15 148 (077-284)



















i
























bull History

bull Lung diseases


bull History

bull Lung disease



TOBACCO SMOKE








INFLAMMATION



LUNG CANCER




ndash COPD

ndash Lung cancer









times








bull History

bull Lung disease












bull History

bull Lung diseases

bull COPD









bull Findings






bull Interpretation







Follow up (y)

Po

stb

ron

cho

dila

tor

FEV

1 L

24

25

26

27

28

29

Screen 2 1 2 3 4 5

Sustained Quitters

Continuous Smokers



COPD










bull Asthma

Asthma








32 subjects


10 quit smoking

Lung cancer













200615517-523















Wen et al--2010




Kolappan Gopi--2002

Thank you




Cancer


Lung

Mouth and pharynx

Larynx

Esophagus

Stomach

Pancreas

Liver

Cervix

Bladder

Kidney

Colorectum

Breast




Body mass index






45-74 years







history from women




51 of the cohort




Heavy smokers (12)


Light smokers (88)





Men (n=27292) Women (n=34028)


Percent 422 214 364 913 25 62


Lung cancer


Never 100

1-12 432 (355-523)

13-22 661 (546-802)

23+ 949 (758-1188)

P for trend lt00001

Smoking status

Lung cancer

RR (95 CI)

Never 100

Former 224 (181-278)

Current 585 (499-687)







Body Mass

Index (kgm2)

Never

smokers

Former

smokers

Current

smokers

Adj HR

(95 CI)

Adj HR

(95 CI)

Adj HR

(95 CI)

lt20 100 100 100

20-lt24 102 (071-146) 092 (057-148) 081 (067-099)

24-lt28 072 (046-110) 101 (059-174) 062 (046-082)

28+ 081 (046-144) 097 (044-212) 050 (028-088)

P for trend 008 089 00001



Smoking

status



Never 100 100 100 100

Former 246

(140-432)

197

(148-262)

296

(184-476)

199

(088-452)

Current 721

(484-1075)

520

(422-641)

550

(364-832)

321

(158-651)





1-12 618

(398-958)

365

(282-473)

365

(212-628)

290

(115-727)

13-22 792

(501-1253)

639

(498-820)

541

(323-905)

221

(071-686)

23+ 1112

(660-1870)

853

(635-1150)

901

(504-1610)

637

(210-1930)

P trend lt00001 lt00001 lt00001 00001




of lung cancer





damage





weights



developed world



Obesity

Western diet

Physical inactivity

Smoking







GST enzymes







GSTP1 polymorphism







Smokers














us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang













Tobacco deaths 2000

Developed 2 million




countries

Tobacco deaths 2030

3 million

7 million




0

10

20

30

40

50

60

70

0 10 20 30 40 50 60 70 80 90 100

0

5

10

15

20

25

30

35

40

of deaths caused by

smoking



19601900 1920 1940 1980 2000

male smokers

female smokers

male deaths

female deaths



through 2005



0

10

20

30

40

50

60

1965

1974

1979

1983

1985

1990

1992

1994

1995

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

2009

2010

Year

Pre

vale

nce (

)



Men

Women

(52)

(34) (215)

(173)


0

10

20

30

40

50

60

70

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Women

0

10

20

30

40

50

60

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Pre

vale

nce


Australia

Men

0

10

20

30

40

50

60

70

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Women

0

10

20

30

40

50

60

70

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Pre

vale

nce




Romania

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Greece

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Poland

0

5

10

15

20

25

30

35

40

45

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Russia

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female



United Kingdom

United States

Canada

New Zealand

Australia







Greece

Italy

Spain





Community Medicine

Faculty of Medicine


March 23 2012


Singapore

Overview




Active smoking risk

Conclusions

Passive smoking

Secondhand smoke

Involuntary smoking











Acrylamide

Acrylonitrile

13-Butadiene

Isoprene

Nitromethane

Propylene Oxide


Vinyl chloride

4-Aminobiphenyl

Urethane

Benzene

Nitrobenzene

Benzo[a]pyrene

ortho-Toluidine

Dibenzo[ae]pyrene

Dibenzo[ai]pyrene

Dibenzo[al]pyrene






Mainstream Smoke

- Carbon monoxide

- Nitrogen Oxides

- Nicotine

25-15 times as much

37-128 times

13-21 as much

- Benzene

- Formaldehyde

- NNK

- Benz(a)pyrene

- Nickel

- Tar

8-10 times as much

50 times as much

1-22 times as much

25-20 times as much

13-30 times as much

11-157 times













01

1

10H

iray

am

a 199

2W

arte

nb

erg

et

al

200

0R

eyn

old

s e

t a

l 20

04

Ha

nao

ka e

t al

200

4S

an

dle

r e

t al 1

985

Millik

an

et

al 1

998

De

lfin

o e

t al

2000

Scru

bso

le e

t al

2004

Gam

mon

et a

l 200

4S

mit

h e

t al

1994

Mo

rab

ia e

t al 1

996

Zh

ao

et

al

1999

Jo

hn

so

n e

t al

200

0K

ro

pp

et

al

200

2L

isso

wsk

a e

t al 2

00

6M

issed

Ex

po

su

re -

Co

ho

rt

Stu

die

s

Mis

sed

Ex

po

su

re -

Cas

e-C

on

tro

l

Be

tte

r E

xp

osu

re

Asses

sm

en

t



|______________________________________|



|_____________________|

Cohort

|___________________________|

Case-control






















cancerrdquo



2005 1

Surgeon Generals

Report 20062


(95 CI)

N Relative Risk

(95 CI)

All studies 19 125 (108-144) 21 120 (108-135)

Premenopausal

Women lt 50

14 168 (131-215) 11 164 (125-214)

Premenopausal

with lifetime

exposure

assessment

5 220 (169-287) 6 185 (119-287)


Balancing Concerns








Ed



0

50

100

150

200

250

USA 1994

Europe 1998

Sweden 1998

Germany 1998

China 1999

Germany 2000

China 2000

Canada 2001

Excess Lung

Cancer Risk

(Percentage)


Higher Exposure

Work Only -

Higher Exposure


+1-25

+35-220 +50-210























Teachers Cohort[48]

Adjusted HR

(95 CI)

Womenrsquos Health


Adjusted HR (95

CI)


exposure

100 100







126 (099-160) 132(104-167)





























Exposure



40+ cigday

138 (105-183)

174 (115-262)



205 (120-349)


gt20 cigday 183 (129-261)


Initiation 10-14 146 (111-193)

148 (103-213)


(premeno) 39 (15-99)


Hanaoka et al 2004



Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)






Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)

Pooled

Analysis

Never

active

100 100 100 100

lt20 105 (086-128) 123 (103-146) 091 (072-116) 110 (089-135)

gt20 149 (108-204) 142 (116-174) 129 (089-186) 088 (069-113)






initiation

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137)

Al-Delaimy(2004) 129 (097-171)

Reynolds (2004) 117 (105-130)

Lawlor (2004)

Gram (2005) 148 (103-213)

Olson (2005) 112 (092-136)

Cui (2006) 111 (097-128)

Ha (2007) 148 (077-284)

8 of 8 positive

4 of 8 Stat Sig




initiation

Longest duration

before pregnancy

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131)

Al-Delaimy(2004) 129 (097-171) 110 (080-152)

Reynolds (2004) 117 (105-130) 113 (100-125)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137)

Olson (2005) 112 (092-136) 121 (101-125)

Cui (2006) 111 (097-128) 113 (101-125)

Ha (2007) 148 (077-284) 178 (127-249)11

9 of 9 positive

4 of 9 Stat Sig




initiation

Longest duration

before pregnancy

Longest

duration

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189)

Ha (2007) 148 (077-284) 178 (127-249)11

6 of 6 positive

3 of 6 Stat Sig




initiation

Longest duration

Before pregnancy

Longest

duration

Highest pack-

years

Calle (1994) 159 (117-215) 138 (105-183)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133) 125 (106-147)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174) 146 (111-193)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138) 115 (096-137)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189) 117 (102-134)

Ha (2007) 148 (077-284) 178 (127-249)11


5 of 5 positive




First Author Year



Relative Risk

(95 CI)

Reynolds et al (2004) lt20 117 (105-130)

Olson et al (2005) lt19 112 (092-136)

Xue et al (2011) lt18 104 (099-111)

Cui et al (2006) lt16 111 (097-128)


Gram et al (2005) lt15 148 (103-213)

Ha et al (2007) lt15 148 (077-284)



















i
























bull History

bull Lung diseases


bull History

bull Lung disease



TOBACCO SMOKE








INFLAMMATION



LUNG CANCER




ndash COPD

ndash Lung cancer









times








bull History

bull Lung disease












bull History

bull Lung diseases

bull COPD









bull Findings






bull Interpretation







Follow up (y)

Po

stb

ron

cho

dila

tor

FEV

1 L

24

25

26

27

28

29

Screen 2 1 2 3 4 5

Sustained Quitters

Continuous Smokers



COPD










bull Asthma

Asthma








32 subjects


10 quit smoking

Lung cancer













200615517-523















Wen et al--2010




Kolappan Gopi--2002

Thank you




Cancer


Lung

Mouth and pharynx

Larynx

Esophagus

Stomach

Pancreas

Liver

Cervix

Bladder

Kidney

Colorectum

Breast




Body mass index






45-74 years







history from women




51 of the cohort




Heavy smokers (12)


Light smokers (88)





Men (n=27292) Women (n=34028)


Percent 422 214 364 913 25 62


Lung cancer


Never 100

1-12 432 (355-523)

13-22 661 (546-802)

23+ 949 (758-1188)

P for trend lt00001

Smoking status

Lung cancer

RR (95 CI)

Never 100

Former 224 (181-278)

Current 585 (499-687)







Body Mass

Index (kgm2)

Never

smokers

Former

smokers

Current

smokers

Adj HR

(95 CI)

Adj HR

(95 CI)

Adj HR

(95 CI)

lt20 100 100 100

20-lt24 102 (071-146) 092 (057-148) 081 (067-099)

24-lt28 072 (046-110) 101 (059-174) 062 (046-082)

28+ 081 (046-144) 097 (044-212) 050 (028-088)

P for trend 008 089 00001



Smoking

status



Never 100 100 100 100

Former 246

(140-432)

197

(148-262)

296

(184-476)

199

(088-452)

Current 721

(484-1075)

520

(422-641)

550

(364-832)

321

(158-651)





1-12 618

(398-958)

365

(282-473)

365

(212-628)

290

(115-727)

13-22 792

(501-1253)

639

(498-820)

541

(323-905)

221

(071-686)

23+ 1112

(660-1870)

853

(635-1150)

901

(504-1610)

637

(210-1930)

P trend lt00001 lt00001 lt00001 00001




of lung cancer





damage





weights



developed world



Obesity

Western diet

Physical inactivity

Smoking







GST enzymes







GSTP1 polymorphism







Smokers














us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang









0

10

20

30

40

50

60

70

0 10 20 30 40 50 60 70 80 90 100

0

5

10

15

20

25

30

35

40

of deaths caused by

smoking



19601900 1920 1940 1980 2000

male smokers

female smokers

male deaths

female deaths



through 2005



0

10

20

30

40

50

60

1965

1974

1979

1983

1985

1990

1992

1994

1995

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

2009

2010

Year

Pre

vale

nce (

)



Men

Women

(52)

(34) (215)

(173)


0

10

20

30

40

50

60

70

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Women

0

10

20

30

40

50

60

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Pre

vale

nce


Australia

Men

0

10

20

30

40

50

60

70

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Women

0

10

20

30

40

50

60

70

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Pre

vale

nce




Romania

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Greece

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Poland

0

5

10

15

20

25

30

35

40

45

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Russia

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female



United Kingdom

United States

Canada

New Zealand

Australia







Greece

Italy

Spain





Community Medicine

Faculty of Medicine


March 23 2012


Singapore

Overview




Active smoking risk

Conclusions

Passive smoking

Secondhand smoke

Involuntary smoking











Acrylamide

Acrylonitrile

13-Butadiene

Isoprene

Nitromethane

Propylene Oxide


Vinyl chloride

4-Aminobiphenyl

Urethane

Benzene

Nitrobenzene

Benzo[a]pyrene

ortho-Toluidine

Dibenzo[ae]pyrene

Dibenzo[ai]pyrene

Dibenzo[al]pyrene






Mainstream Smoke

- Carbon monoxide

- Nitrogen Oxides

- Nicotine

25-15 times as much

37-128 times

13-21 as much

- Benzene

- Formaldehyde

- NNK

- Benz(a)pyrene

- Nickel

- Tar

8-10 times as much

50 times as much

1-22 times as much

25-20 times as much

13-30 times as much

11-157 times













01

1

10H

iray

am

a 199

2W

arte

nb

erg

et

al

200

0R

eyn

old

s e

t a

l 20

04

Ha

nao

ka e

t al

200

4S

an

dle

r e

t al 1

985

Millik

an

et

al 1

998

De

lfin

o e

t al

2000

Scru

bso

le e

t al

2004

Gam

mon

et a

l 200

4S

mit

h e

t al

1994

Mo

rab

ia e

t al 1

996

Zh

ao

et

al

1999

Jo

hn

so

n e

t al

200

0K

ro

pp

et

al

200

2L

isso

wsk

a e

t al 2

00

6M

issed

Ex

po

su

re -

Co

ho

rt

Stu

die

s

Mis

sed

Ex

po

su

re -

Cas

e-C

on

tro

l

Be

tte

r E

xp

osu

re

Asses

sm

en

t



|______________________________________|



|_____________________|

Cohort

|___________________________|

Case-control






















cancerrdquo



2005 1

Surgeon Generals

Report 20062


(95 CI)

N Relative Risk

(95 CI)

All studies 19 125 (108-144) 21 120 (108-135)

Premenopausal

Women lt 50

14 168 (131-215) 11 164 (125-214)

Premenopausal

with lifetime

exposure

assessment

5 220 (169-287) 6 185 (119-287)


Balancing Concerns








Ed



0

50

100

150

200

250

USA 1994

Europe 1998

Sweden 1998

Germany 1998

China 1999

Germany 2000

China 2000

Canada 2001

Excess Lung

Cancer Risk

(Percentage)


Higher Exposure

Work Only -

Higher Exposure


+1-25

+35-220 +50-210























Teachers Cohort[48]

Adjusted HR

(95 CI)

Womenrsquos Health


Adjusted HR (95

CI)


exposure

100 100







126 (099-160) 132(104-167)





























Exposure



40+ cigday

138 (105-183)

174 (115-262)



205 (120-349)


gt20 cigday 183 (129-261)


Initiation 10-14 146 (111-193)

148 (103-213)


(premeno) 39 (15-99)


Hanaoka et al 2004



Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)






Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)

Pooled

Analysis

Never

active

100 100 100 100

lt20 105 (086-128) 123 (103-146) 091 (072-116) 110 (089-135)

gt20 149 (108-204) 142 (116-174) 129 (089-186) 088 (069-113)






initiation

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137)

Al-Delaimy(2004) 129 (097-171)

Reynolds (2004) 117 (105-130)

Lawlor (2004)

Gram (2005) 148 (103-213)

Olson (2005) 112 (092-136)

Cui (2006) 111 (097-128)

Ha (2007) 148 (077-284)

8 of 8 positive

4 of 8 Stat Sig




initiation

Longest duration

before pregnancy

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131)

Al-Delaimy(2004) 129 (097-171) 110 (080-152)

Reynolds (2004) 117 (105-130) 113 (100-125)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137)

Olson (2005) 112 (092-136) 121 (101-125)

Cui (2006) 111 (097-128) 113 (101-125)

Ha (2007) 148 (077-284) 178 (127-249)11

9 of 9 positive

4 of 9 Stat Sig




initiation

Longest duration

before pregnancy

Longest

duration

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189)

Ha (2007) 148 (077-284) 178 (127-249)11

6 of 6 positive

3 of 6 Stat Sig




initiation

Longest duration

Before pregnancy

Longest

duration

Highest pack-

years

Calle (1994) 159 (117-215) 138 (105-183)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133) 125 (106-147)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174) 146 (111-193)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138) 115 (096-137)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189) 117 (102-134)

Ha (2007) 148 (077-284) 178 (127-249)11


5 of 5 positive




First Author Year



Relative Risk

(95 CI)

Reynolds et al (2004) lt20 117 (105-130)

Olson et al (2005) lt19 112 (092-136)

Xue et al (2011) lt18 104 (099-111)

Cui et al (2006) lt16 111 (097-128)


Gram et al (2005) lt15 148 (103-213)

Ha et al (2007) lt15 148 (077-284)



















i
























bull History

bull Lung diseases


bull History

bull Lung disease



TOBACCO SMOKE








INFLAMMATION



LUNG CANCER




ndash COPD

ndash Lung cancer









times








bull History

bull Lung disease












bull History

bull Lung diseases

bull COPD









bull Findings






bull Interpretation







Follow up (y)

Po

stb

ron

cho

dila

tor

FEV

1 L

24

25

26

27

28

29

Screen 2 1 2 3 4 5

Sustained Quitters

Continuous Smokers



COPD










bull Asthma

Asthma








32 subjects


10 quit smoking

Lung cancer













200615517-523















Wen et al--2010




Kolappan Gopi--2002

Thank you




Cancer


Lung

Mouth and pharynx

Larynx

Esophagus

Stomach

Pancreas

Liver

Cervix

Bladder

Kidney

Colorectum

Breast




Body mass index






45-74 years







history from women




51 of the cohort




Heavy smokers (12)


Light smokers (88)





Men (n=27292) Women (n=34028)


Percent 422 214 364 913 25 62


Lung cancer


Never 100

1-12 432 (355-523)

13-22 661 (546-802)

23+ 949 (758-1188)

P for trend lt00001

Smoking status

Lung cancer

RR (95 CI)

Never 100

Former 224 (181-278)

Current 585 (499-687)







Body Mass

Index (kgm2)

Never

smokers

Former

smokers

Current

smokers

Adj HR

(95 CI)

Adj HR

(95 CI)

Adj HR

(95 CI)

lt20 100 100 100

20-lt24 102 (071-146) 092 (057-148) 081 (067-099)

24-lt28 072 (046-110) 101 (059-174) 062 (046-082)

28+ 081 (046-144) 097 (044-212) 050 (028-088)

P for trend 008 089 00001



Smoking

status



Never 100 100 100 100

Former 246

(140-432)

197

(148-262)

296

(184-476)

199

(088-452)

Current 721

(484-1075)

520

(422-641)

550

(364-832)

321

(158-651)





1-12 618

(398-958)

365

(282-473)

365

(212-628)

290

(115-727)

13-22 792

(501-1253)

639

(498-820)

541

(323-905)

221

(071-686)

23+ 1112

(660-1870)

853

(635-1150)

901

(504-1610)

637

(210-1930)

P trend lt00001 lt00001 lt00001 00001




of lung cancer





damage





weights



developed world



Obesity

Western diet

Physical inactivity

Smoking







GST enzymes







GSTP1 polymorphism







Smokers














us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang









0

10

20

30

40

50

60

1965

1974

1979

1983

1985

1990

1992

1994

1995

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

2009

2010

Year

Pre

vale

nce (

)



Men

Women

(52)

(34) (215)

(173)


0

10

20

30

40

50

60

70

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Women

0

10

20

30

40

50

60

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Pre

vale

nce


Australia

Men

0

10

20

30

40

50

60

70

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Women

0

10

20

30

40

50

60

70

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Pre

vale

nce




Romania

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Greece

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Poland

0

5

10

15

20

25

30

35

40

45

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Russia

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female



United Kingdom

United States

Canada

New Zealand

Australia







Greece

Italy

Spain





Community Medicine

Faculty of Medicine


March 23 2012


Singapore

Overview




Active smoking risk

Conclusions

Passive smoking

Secondhand smoke

Involuntary smoking











Acrylamide

Acrylonitrile

13-Butadiene

Isoprene

Nitromethane

Propylene Oxide


Vinyl chloride

4-Aminobiphenyl

Urethane

Benzene

Nitrobenzene

Benzo[a]pyrene

ortho-Toluidine

Dibenzo[ae]pyrene

Dibenzo[ai]pyrene

Dibenzo[al]pyrene






Mainstream Smoke

- Carbon monoxide

- Nitrogen Oxides

- Nicotine

25-15 times as much

37-128 times

13-21 as much

- Benzene

- Formaldehyde

- NNK

- Benz(a)pyrene

- Nickel

- Tar

8-10 times as much

50 times as much

1-22 times as much

25-20 times as much

13-30 times as much

11-157 times













01

1

10H

iray

am

a 199

2W

arte

nb

erg

et

al

200

0R

eyn

old

s e

t a

l 20

04

Ha

nao

ka e

t al

200

4S

an

dle

r e

t al 1

985

Millik

an

et

al 1

998

De

lfin

o e

t al

2000

Scru

bso

le e

t al

2004

Gam

mon

et a

l 200

4S

mit

h e

t al

1994

Mo

rab

ia e

t al 1

996

Zh

ao

et

al

1999

Jo

hn

so

n e

t al

200

0K

ro

pp

et

al

200

2L

isso

wsk

a e

t al 2

00

6M

issed

Ex

po

su

re -

Co

ho

rt

Stu

die

s

Mis

sed

Ex

po

su

re -

Cas

e-C

on

tro

l

Be

tte

r E

xp

osu

re

Asses

sm

en

t



|______________________________________|



|_____________________|

Cohort

|___________________________|

Case-control






















cancerrdquo



2005 1

Surgeon Generals

Report 20062


(95 CI)

N Relative Risk

(95 CI)

All studies 19 125 (108-144) 21 120 (108-135)

Premenopausal

Women lt 50

14 168 (131-215) 11 164 (125-214)

Premenopausal

with lifetime

exposure

assessment

5 220 (169-287) 6 185 (119-287)


Balancing Concerns








Ed



0

50

100

150

200

250

USA 1994

Europe 1998

Sweden 1998

Germany 1998

China 1999

Germany 2000

China 2000

Canada 2001

Excess Lung

Cancer Risk

(Percentage)


Higher Exposure

Work Only -

Higher Exposure


+1-25

+35-220 +50-210























Teachers Cohort[48]

Adjusted HR

(95 CI)

Womenrsquos Health


Adjusted HR (95

CI)


exposure

100 100







126 (099-160) 132(104-167)





























Exposure



40+ cigday

138 (105-183)

174 (115-262)



205 (120-349)


gt20 cigday 183 (129-261)


Initiation 10-14 146 (111-193)

148 (103-213)


(premeno) 39 (15-99)


Hanaoka et al 2004



Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)






Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)

Pooled

Analysis

Never

active

100 100 100 100

lt20 105 (086-128) 123 (103-146) 091 (072-116) 110 (089-135)

gt20 149 (108-204) 142 (116-174) 129 (089-186) 088 (069-113)






initiation

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137)

Al-Delaimy(2004) 129 (097-171)

Reynolds (2004) 117 (105-130)

Lawlor (2004)

Gram (2005) 148 (103-213)

Olson (2005) 112 (092-136)

Cui (2006) 111 (097-128)

Ha (2007) 148 (077-284)

8 of 8 positive

4 of 8 Stat Sig




initiation

Longest duration

before pregnancy

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131)

Al-Delaimy(2004) 129 (097-171) 110 (080-152)

Reynolds (2004) 117 (105-130) 113 (100-125)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137)

Olson (2005) 112 (092-136) 121 (101-125)

Cui (2006) 111 (097-128) 113 (101-125)

Ha (2007) 148 (077-284) 178 (127-249)11

9 of 9 positive

4 of 9 Stat Sig




initiation

Longest duration

before pregnancy

Longest

duration

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189)

Ha (2007) 148 (077-284) 178 (127-249)11

6 of 6 positive

3 of 6 Stat Sig




initiation

Longest duration

Before pregnancy

Longest

duration

Highest pack-

years

Calle (1994) 159 (117-215) 138 (105-183)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133) 125 (106-147)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174) 146 (111-193)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138) 115 (096-137)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189) 117 (102-134)

Ha (2007) 148 (077-284) 178 (127-249)11


5 of 5 positive




First Author Year



Relative Risk

(95 CI)

Reynolds et al (2004) lt20 117 (105-130)

Olson et al (2005) lt19 112 (092-136)

Xue et al (2011) lt18 104 (099-111)

Cui et al (2006) lt16 111 (097-128)


Gram et al (2005) lt15 148 (103-213)

Ha et al (2007) lt15 148 (077-284)



















i
























bull History

bull Lung diseases


bull History

bull Lung disease



TOBACCO SMOKE








INFLAMMATION



LUNG CANCER




ndash COPD

ndash Lung cancer









times








bull History

bull Lung disease












bull History

bull Lung diseases

bull COPD









bull Findings






bull Interpretation







Follow up (y)

Po

stb

ron

cho

dila

tor

FEV

1 L

24

25

26

27

28

29

Screen 2 1 2 3 4 5

Sustained Quitters

Continuous Smokers



COPD










bull Asthma

Asthma








32 subjects


10 quit smoking

Lung cancer













200615517-523















Wen et al--2010




Kolappan Gopi--2002

Thank you




Cancer


Lung

Mouth and pharynx

Larynx

Esophagus

Stomach

Pancreas

Liver

Cervix

Bladder

Kidney

Colorectum

Breast




Body mass index






45-74 years







history from women




51 of the cohort




Heavy smokers (12)


Light smokers (88)





Men (n=27292) Women (n=34028)


Percent 422 214 364 913 25 62


Lung cancer


Never 100

1-12 432 (355-523)

13-22 661 (546-802)

23+ 949 (758-1188)

P for trend lt00001

Smoking status

Lung cancer

RR (95 CI)

Never 100

Former 224 (181-278)

Current 585 (499-687)







Body Mass

Index (kgm2)

Never

smokers

Former

smokers

Current

smokers

Adj HR

(95 CI)

Adj HR

(95 CI)

Adj HR

(95 CI)

lt20 100 100 100

20-lt24 102 (071-146) 092 (057-148) 081 (067-099)

24-lt28 072 (046-110) 101 (059-174) 062 (046-082)

28+ 081 (046-144) 097 (044-212) 050 (028-088)

P for trend 008 089 00001



Smoking

status



Never 100 100 100 100

Former 246

(140-432)

197

(148-262)

296

(184-476)

199

(088-452)

Current 721

(484-1075)

520

(422-641)

550

(364-832)

321

(158-651)





1-12 618

(398-958)

365

(282-473)

365

(212-628)

290

(115-727)

13-22 792

(501-1253)

639

(498-820)

541

(323-905)

221

(071-686)

23+ 1112

(660-1870)

853

(635-1150)

901

(504-1610)

637

(210-1930)

P trend lt00001 lt00001 lt00001 00001




of lung cancer





damage





weights



developed world



Obesity

Western diet

Physical inactivity

Smoking







GST enzymes







GSTP1 polymorphism







Smokers














us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang








0

10

20

30

40

50

60

70

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Women

0

10

20

30

40

50

60

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Pre

vale

nce


Australia

Men

0

10

20

30

40

50

60

70

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Women

0

10

20

30

40

50

60

70

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Pre

vale

nce




Romania

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Greece

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Poland

0

5

10

15

20

25

30

35

40

45

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Russia

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female



United Kingdom

United States

Canada

New Zealand

Australia







Greece

Italy

Spain





Community Medicine

Faculty of Medicine


March 23 2012


Singapore

Overview




Active smoking risk

Conclusions

Passive smoking

Secondhand smoke

Involuntary smoking











Acrylamide

Acrylonitrile

13-Butadiene

Isoprene

Nitromethane

Propylene Oxide


Vinyl chloride

4-Aminobiphenyl

Urethane

Benzene

Nitrobenzene

Benzo[a]pyrene

ortho-Toluidine

Dibenzo[ae]pyrene

Dibenzo[ai]pyrene

Dibenzo[al]pyrene






Mainstream Smoke

- Carbon monoxide

- Nitrogen Oxides

- Nicotine

25-15 times as much

37-128 times

13-21 as much

- Benzene

- Formaldehyde

- NNK

- Benz(a)pyrene

- Nickel

- Tar

8-10 times as much

50 times as much

1-22 times as much

25-20 times as much

13-30 times as much

11-157 times













01

1

10H

iray

am

a 199

2W

arte

nb

erg

et

al

200

0R

eyn

old

s e

t a

l 20

04

Ha

nao

ka e

t al

200

4S

an

dle

r e

t al 1

985

Millik

an

et

al 1

998

De

lfin

o e

t al

2000

Scru

bso

le e

t al

2004

Gam

mon

et a

l 200

4S

mit

h e

t al

1994

Mo

rab

ia e

t al 1

996

Zh

ao

et

al

1999

Jo

hn

so

n e

t al

200

0K

ro

pp

et

al

200

2L

isso

wsk

a e

t al 2

00

6M

issed

Ex

po

su

re -

Co

ho

rt

Stu

die

s

Mis

sed

Ex

po

su

re -

Cas

e-C

on

tro

l

Be

tte

r E

xp

osu

re

Asses

sm

en

t



|______________________________________|



|_____________________|

Cohort

|___________________________|

Case-control






















cancerrdquo



2005 1

Surgeon Generals

Report 20062


(95 CI)

N Relative Risk

(95 CI)

All studies 19 125 (108-144) 21 120 (108-135)

Premenopausal

Women lt 50

14 168 (131-215) 11 164 (125-214)

Premenopausal

with lifetime

exposure

assessment

5 220 (169-287) 6 185 (119-287)


Balancing Concerns








Ed



0

50

100

150

200

250

USA 1994

Europe 1998

Sweden 1998

Germany 1998

China 1999

Germany 2000

China 2000

Canada 2001

Excess Lung

Cancer Risk

(Percentage)


Higher Exposure

Work Only -

Higher Exposure


+1-25

+35-220 +50-210























Teachers Cohort[48]

Adjusted HR

(95 CI)

Womenrsquos Health


Adjusted HR (95

CI)


exposure

100 100







126 (099-160) 132(104-167)





























Exposure



40+ cigday

138 (105-183)

174 (115-262)



205 (120-349)


gt20 cigday 183 (129-261)


Initiation 10-14 146 (111-193)

148 (103-213)


(premeno) 39 (15-99)


Hanaoka et al 2004



Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)






Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)

Pooled

Analysis

Never

active

100 100 100 100

lt20 105 (086-128) 123 (103-146) 091 (072-116) 110 (089-135)

gt20 149 (108-204) 142 (116-174) 129 (089-186) 088 (069-113)






initiation

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137)

Al-Delaimy(2004) 129 (097-171)

Reynolds (2004) 117 (105-130)

Lawlor (2004)

Gram (2005) 148 (103-213)

Olson (2005) 112 (092-136)

Cui (2006) 111 (097-128)

Ha (2007) 148 (077-284)

8 of 8 positive

4 of 8 Stat Sig




initiation

Longest duration

before pregnancy

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131)

Al-Delaimy(2004) 129 (097-171) 110 (080-152)

Reynolds (2004) 117 (105-130) 113 (100-125)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137)

Olson (2005) 112 (092-136) 121 (101-125)

Cui (2006) 111 (097-128) 113 (101-125)

Ha (2007) 148 (077-284) 178 (127-249)11

9 of 9 positive

4 of 9 Stat Sig




initiation

Longest duration

before pregnancy

Longest

duration

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189)

Ha (2007) 148 (077-284) 178 (127-249)11

6 of 6 positive

3 of 6 Stat Sig




initiation

Longest duration

Before pregnancy

Longest

duration

Highest pack-

years

Calle (1994) 159 (117-215) 138 (105-183)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133) 125 (106-147)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174) 146 (111-193)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138) 115 (096-137)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189) 117 (102-134)

Ha (2007) 148 (077-284) 178 (127-249)11


5 of 5 positive




First Author Year



Relative Risk

(95 CI)

Reynolds et al (2004) lt20 117 (105-130)

Olson et al (2005) lt19 112 (092-136)

Xue et al (2011) lt18 104 (099-111)

Cui et al (2006) lt16 111 (097-128)


Gram et al (2005) lt15 148 (103-213)

Ha et al (2007) lt15 148 (077-284)



















i
























bull History

bull Lung diseases


bull History

bull Lung disease



TOBACCO SMOKE








INFLAMMATION



LUNG CANCER




ndash COPD

ndash Lung cancer









times








bull History

bull Lung disease












bull History

bull Lung diseases

bull COPD









bull Findings






bull Interpretation







Follow up (y)

Po

stb

ron

cho

dila

tor

FEV

1 L

24

25

26

27

28

29

Screen 2 1 2 3 4 5

Sustained Quitters

Continuous Smokers



COPD










bull Asthma

Asthma








32 subjects


10 quit smoking

Lung cancer













200615517-523















Wen et al--2010




Kolappan Gopi--2002

Thank you




Cancer


Lung

Mouth and pharynx

Larynx

Esophagus

Stomach

Pancreas

Liver

Cervix

Bladder

Kidney

Colorectum

Breast




Body mass index






45-74 years







history from women




51 of the cohort




Heavy smokers (12)


Light smokers (88)





Men (n=27292) Women (n=34028)


Percent 422 214 364 913 25 62


Lung cancer


Never 100

1-12 432 (355-523)

13-22 661 (546-802)

23+ 949 (758-1188)

P for trend lt00001

Smoking status

Lung cancer

RR (95 CI)

Never 100

Former 224 (181-278)

Current 585 (499-687)







Body Mass

Index (kgm2)

Never

smokers

Former

smokers

Current

smokers

Adj HR

(95 CI)

Adj HR

(95 CI)

Adj HR

(95 CI)

lt20 100 100 100

20-lt24 102 (071-146) 092 (057-148) 081 (067-099)

24-lt28 072 (046-110) 101 (059-174) 062 (046-082)

28+ 081 (046-144) 097 (044-212) 050 (028-088)

P for trend 008 089 00001



Smoking

status



Never 100 100 100 100

Former 246

(140-432)

197

(148-262)

296

(184-476)

199

(088-452)

Current 721

(484-1075)

520

(422-641)

550

(364-832)

321

(158-651)





1-12 618

(398-958)

365

(282-473)

365

(212-628)

290

(115-727)

13-22 792

(501-1253)

639

(498-820)

541

(323-905)

221

(071-686)

23+ 1112

(660-1870)

853

(635-1150)

901

(504-1610)

637

(210-1930)

P trend lt00001 lt00001 lt00001 00001




of lung cancer





damage





weights



developed world



Obesity

Western diet

Physical inactivity

Smoking







GST enzymes







GSTP1 polymorphism







Smokers














us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang







Australia

Men

0

10

20

30

40

50

60

70

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Women

0

10

20

30

40

50

60

70

46-

50

51-

55

56-

60

61-

65

66-

70

71-

75

76-

80

81-

85

86-

90

91-

95

96-

00

01-

05

Year

Pre

vale

nce




Romania

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Greece

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Poland

0

5

10

15

20

25

30

35

40

45

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Russia

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female



United Kingdom

United States

Canada

New Zealand

Australia







Greece

Italy

Spain





Community Medicine

Faculty of Medicine


March 23 2012


Singapore

Overview




Active smoking risk

Conclusions

Passive smoking

Secondhand smoke

Involuntary smoking











Acrylamide

Acrylonitrile

13-Butadiene

Isoprene

Nitromethane

Propylene Oxide


Vinyl chloride

4-Aminobiphenyl

Urethane

Benzene

Nitrobenzene

Benzo[a]pyrene

ortho-Toluidine

Dibenzo[ae]pyrene

Dibenzo[ai]pyrene

Dibenzo[al]pyrene






Mainstream Smoke

- Carbon monoxide

- Nitrogen Oxides

- Nicotine

25-15 times as much

37-128 times

13-21 as much

- Benzene

- Formaldehyde

- NNK

- Benz(a)pyrene

- Nickel

- Tar

8-10 times as much

50 times as much

1-22 times as much

25-20 times as much

13-30 times as much

11-157 times













01

1

10H

iray

am

a 199

2W

arte

nb

erg

et

al

200

0R

eyn

old

s e

t a

l 20

04

Ha

nao

ka e

t al

200

4S

an

dle

r e

t al 1

985

Millik

an

et

al 1

998

De

lfin

o e

t al

2000

Scru

bso

le e

t al

2004

Gam

mon

et a

l 200

4S

mit

h e

t al

1994

Mo

rab

ia e

t al 1

996

Zh

ao

et

al

1999

Jo

hn

so

n e

t al

200

0K

ro

pp

et

al

200

2L

isso

wsk

a e

t al 2

00

6M

issed

Ex

po

su

re -

Co

ho

rt

Stu

die

s

Mis

sed

Ex

po

su

re -

Cas

e-C

on

tro

l

Be

tte

r E

xp

osu

re

Asses

sm

en

t



|______________________________________|



|_____________________|

Cohort

|___________________________|

Case-control






















cancerrdquo



2005 1

Surgeon Generals

Report 20062


(95 CI)

N Relative Risk

(95 CI)

All studies 19 125 (108-144) 21 120 (108-135)

Premenopausal

Women lt 50

14 168 (131-215) 11 164 (125-214)

Premenopausal

with lifetime

exposure

assessment

5 220 (169-287) 6 185 (119-287)


Balancing Concerns








Ed



0

50

100

150

200

250

USA 1994

Europe 1998

Sweden 1998

Germany 1998

China 1999

Germany 2000

China 2000

Canada 2001

Excess Lung

Cancer Risk

(Percentage)


Higher Exposure

Work Only -

Higher Exposure


+1-25

+35-220 +50-210























Teachers Cohort[48]

Adjusted HR

(95 CI)

Womenrsquos Health


Adjusted HR (95

CI)


exposure

100 100







126 (099-160) 132(104-167)





























Exposure



40+ cigday

138 (105-183)

174 (115-262)



205 (120-349)


gt20 cigday 183 (129-261)


Initiation 10-14 146 (111-193)

148 (103-213)


(premeno) 39 (15-99)


Hanaoka et al 2004



Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)






Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)

Pooled

Analysis

Never

active

100 100 100 100

lt20 105 (086-128) 123 (103-146) 091 (072-116) 110 (089-135)

gt20 149 (108-204) 142 (116-174) 129 (089-186) 088 (069-113)






initiation

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137)

Al-Delaimy(2004) 129 (097-171)

Reynolds (2004) 117 (105-130)

Lawlor (2004)

Gram (2005) 148 (103-213)

Olson (2005) 112 (092-136)

Cui (2006) 111 (097-128)

Ha (2007) 148 (077-284)

8 of 8 positive

4 of 8 Stat Sig




initiation

Longest duration

before pregnancy

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131)

Al-Delaimy(2004) 129 (097-171) 110 (080-152)

Reynolds (2004) 117 (105-130) 113 (100-125)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137)

Olson (2005) 112 (092-136) 121 (101-125)

Cui (2006) 111 (097-128) 113 (101-125)

Ha (2007) 148 (077-284) 178 (127-249)11

9 of 9 positive

4 of 9 Stat Sig




initiation

Longest duration

before pregnancy

Longest

duration

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189)

Ha (2007) 148 (077-284) 178 (127-249)11

6 of 6 positive

3 of 6 Stat Sig




initiation

Longest duration

Before pregnancy

Longest

duration

Highest pack-

years

Calle (1994) 159 (117-215) 138 (105-183)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133) 125 (106-147)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174) 146 (111-193)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138) 115 (096-137)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189) 117 (102-134)

Ha (2007) 148 (077-284) 178 (127-249)11


5 of 5 positive




First Author Year



Relative Risk

(95 CI)

Reynolds et al (2004) lt20 117 (105-130)

Olson et al (2005) lt19 112 (092-136)

Xue et al (2011) lt18 104 (099-111)

Cui et al (2006) lt16 111 (097-128)


Gram et al (2005) lt15 148 (103-213)

Ha et al (2007) lt15 148 (077-284)



















i
























bull History

bull Lung diseases


bull History

bull Lung disease



TOBACCO SMOKE








INFLAMMATION



LUNG CANCER




ndash COPD

ndash Lung cancer









times








bull History

bull Lung disease












bull History

bull Lung diseases

bull COPD









bull Findings






bull Interpretation







Follow up (y)

Po

stb

ron

cho

dila

tor

FEV

1 L

24

25

26

27

28

29

Screen 2 1 2 3 4 5

Sustained Quitters

Continuous Smokers



COPD










bull Asthma

Asthma








32 subjects


10 quit smoking

Lung cancer













200615517-523















Wen et al--2010




Kolappan Gopi--2002

Thank you




Cancer


Lung

Mouth and pharynx

Larynx

Esophagus

Stomach

Pancreas

Liver

Cervix

Bladder

Kidney

Colorectum

Breast




Body mass index






45-74 years







history from women




51 of the cohort




Heavy smokers (12)


Light smokers (88)





Men (n=27292) Women (n=34028)


Percent 422 214 364 913 25 62


Lung cancer


Never 100

1-12 432 (355-523)

13-22 661 (546-802)

23+ 949 (758-1188)

P for trend lt00001

Smoking status

Lung cancer

RR (95 CI)

Never 100

Former 224 (181-278)

Current 585 (499-687)







Body Mass

Index (kgm2)

Never

smokers

Former

smokers

Current

smokers

Adj HR

(95 CI)

Adj HR

(95 CI)

Adj HR

(95 CI)

lt20 100 100 100

20-lt24 102 (071-146) 092 (057-148) 081 (067-099)

24-lt28 072 (046-110) 101 (059-174) 062 (046-082)

28+ 081 (046-144) 097 (044-212) 050 (028-088)

P for trend 008 089 00001



Smoking

status



Never 100 100 100 100

Former 246

(140-432)

197

(148-262)

296

(184-476)

199

(088-452)

Current 721

(484-1075)

520

(422-641)

550

(364-832)

321

(158-651)





1-12 618

(398-958)

365

(282-473)

365

(212-628)

290

(115-727)

13-22 792

(501-1253)

639

(498-820)

541

(323-905)

221

(071-686)

23+ 1112

(660-1870)

853

(635-1150)

901

(504-1610)

637

(210-1930)

P trend lt00001 lt00001 lt00001 00001




of lung cancer





damage





weights



developed world



Obesity

Western diet

Physical inactivity

Smoking







GST enzymes







GSTP1 polymorphism







Smokers














us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang









Romania

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Greece

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Poland

0

5

10

15

20

25

30

35

40

45

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female

Russia

0

5

10

15

20

25

30

35

40

45

50

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005

Perc

ent

Male

Female



United Kingdom

United States

Canada

New Zealand

Australia







Greece

Italy

Spain





Community Medicine

Faculty of Medicine


March 23 2012


Singapore

Overview




Active smoking risk

Conclusions

Passive smoking

Secondhand smoke

Involuntary smoking











Acrylamide

Acrylonitrile

13-Butadiene

Isoprene

Nitromethane

Propylene Oxide


Vinyl chloride

4-Aminobiphenyl

Urethane

Benzene

Nitrobenzene

Benzo[a]pyrene

ortho-Toluidine

Dibenzo[ae]pyrene

Dibenzo[ai]pyrene

Dibenzo[al]pyrene






Mainstream Smoke

- Carbon monoxide

- Nitrogen Oxides

- Nicotine

25-15 times as much

37-128 times

13-21 as much

- Benzene

- Formaldehyde

- NNK

- Benz(a)pyrene

- Nickel

- Tar

8-10 times as much

50 times as much

1-22 times as much

25-20 times as much

13-30 times as much

11-157 times













01

1

10H

iray

am

a 199

2W

arte

nb

erg

et

al

200

0R

eyn

old

s e

t a

l 20

04

Ha

nao

ka e

t al

200

4S

an

dle

r e

t al 1

985

Millik

an

et

al 1

998

De

lfin

o e

t al

2000

Scru

bso

le e

t al

2004

Gam

mon

et a

l 200

4S

mit

h e

t al

1994

Mo

rab

ia e

t al 1

996

Zh

ao

et

al

1999

Jo

hn

so

n e

t al

200

0K

ro

pp

et

al

200

2L

isso

wsk

a e

t al 2

00

6M

issed

Ex

po

su

re -

Co

ho

rt

Stu

die

s

Mis

sed

Ex

po

su

re -

Cas

e-C

on

tro

l

Be

tte

r E

xp

osu

re

Asses

sm

en

t



|______________________________________|



|_____________________|

Cohort

|___________________________|

Case-control






















cancerrdquo



2005 1

Surgeon Generals

Report 20062


(95 CI)

N Relative Risk

(95 CI)

All studies 19 125 (108-144) 21 120 (108-135)

Premenopausal

Women lt 50

14 168 (131-215) 11 164 (125-214)

Premenopausal

with lifetime

exposure

assessment

5 220 (169-287) 6 185 (119-287)


Balancing Concerns








Ed



0

50

100

150

200

250

USA 1994

Europe 1998

Sweden 1998

Germany 1998

China 1999

Germany 2000

China 2000

Canada 2001

Excess Lung

Cancer Risk

(Percentage)


Higher Exposure

Work Only -

Higher Exposure


+1-25

+35-220 +50-210























Teachers Cohort[48]

Adjusted HR

(95 CI)

Womenrsquos Health


Adjusted HR (95

CI)


exposure

100 100







126 (099-160) 132(104-167)





























Exposure



40+ cigday

138 (105-183)

174 (115-262)



205 (120-349)


gt20 cigday 183 (129-261)


Initiation 10-14 146 (111-193)

148 (103-213)


(premeno) 39 (15-99)


Hanaoka et al 2004



Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)






Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)

Pooled

Analysis

Never

active

100 100 100 100

lt20 105 (086-128) 123 (103-146) 091 (072-116) 110 (089-135)

gt20 149 (108-204) 142 (116-174) 129 (089-186) 088 (069-113)






initiation

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137)

Al-Delaimy(2004) 129 (097-171)

Reynolds (2004) 117 (105-130)

Lawlor (2004)

Gram (2005) 148 (103-213)

Olson (2005) 112 (092-136)

Cui (2006) 111 (097-128)

Ha (2007) 148 (077-284)

8 of 8 positive

4 of 8 Stat Sig




initiation

Longest duration

before pregnancy

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131)

Al-Delaimy(2004) 129 (097-171) 110 (080-152)

Reynolds (2004) 117 (105-130) 113 (100-125)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137)

Olson (2005) 112 (092-136) 121 (101-125)

Cui (2006) 111 (097-128) 113 (101-125)

Ha (2007) 148 (077-284) 178 (127-249)11

9 of 9 positive

4 of 9 Stat Sig




initiation

Longest duration

before pregnancy

Longest

duration

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189)

Ha (2007) 148 (077-284) 178 (127-249)11

6 of 6 positive

3 of 6 Stat Sig




initiation

Longest duration

Before pregnancy

Longest

duration

Highest pack-

years

Calle (1994) 159 (117-215) 138 (105-183)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133) 125 (106-147)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174) 146 (111-193)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138) 115 (096-137)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189) 117 (102-134)

Ha (2007) 148 (077-284) 178 (127-249)11


5 of 5 positive




First Author Year



Relative Risk

(95 CI)

Reynolds et al (2004) lt20 117 (105-130)

Olson et al (2005) lt19 112 (092-136)

Xue et al (2011) lt18 104 (099-111)

Cui et al (2006) lt16 111 (097-128)


Gram et al (2005) lt15 148 (103-213)

Ha et al (2007) lt15 148 (077-284)



















i
























bull History

bull Lung diseases


bull History

bull Lung disease



TOBACCO SMOKE








INFLAMMATION



LUNG CANCER




ndash COPD

ndash Lung cancer









times








bull History

bull Lung disease












bull History

bull Lung diseases

bull COPD









bull Findings






bull Interpretation







Follow up (y)

Po

stb

ron

cho

dila

tor

FEV

1 L

24

25

26

27

28

29

Screen 2 1 2 3 4 5

Sustained Quitters

Continuous Smokers



COPD










bull Asthma

Asthma








32 subjects


10 quit smoking

Lung cancer













200615517-523















Wen et al--2010




Kolappan Gopi--2002

Thank you




Cancer


Lung

Mouth and pharynx

Larynx

Esophagus

Stomach

Pancreas

Liver

Cervix

Bladder

Kidney

Colorectum

Breast




Body mass index






45-74 years







history from women




51 of the cohort




Heavy smokers (12)


Light smokers (88)





Men (n=27292) Women (n=34028)


Percent 422 214 364 913 25 62


Lung cancer


Never 100

1-12 432 (355-523)

13-22 661 (546-802)

23+ 949 (758-1188)

P for trend lt00001

Smoking status

Lung cancer

RR (95 CI)

Never 100

Former 224 (181-278)

Current 585 (499-687)







Body Mass

Index (kgm2)

Never

smokers

Former

smokers

Current

smokers

Adj HR

(95 CI)

Adj HR

(95 CI)

Adj HR

(95 CI)

lt20 100 100 100

20-lt24 102 (071-146) 092 (057-148) 081 (067-099)

24-lt28 072 (046-110) 101 (059-174) 062 (046-082)

28+ 081 (046-144) 097 (044-212) 050 (028-088)

P for trend 008 089 00001



Smoking

status



Never 100 100 100 100

Former 246

(140-432)

197

(148-262)

296

(184-476)

199

(088-452)

Current 721

(484-1075)

520

(422-641)

550

(364-832)

321

(158-651)





1-12 618

(398-958)

365

(282-473)

365

(212-628)

290

(115-727)

13-22 792

(501-1253)

639

(498-820)

541

(323-905)

221

(071-686)

23+ 1112

(660-1870)

853

(635-1150)

901

(504-1610)

637

(210-1930)

P trend lt00001 lt00001 lt00001 00001




of lung cancer





damage





weights



developed world



Obesity

Western diet

Physical inactivity

Smoking







GST enzymes







GSTP1 polymorphism







Smokers














us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang









United Kingdom

United States

Canada

New Zealand

Australia







Greece

Italy

Spain





Community Medicine

Faculty of Medicine


March 23 2012


Singapore

Overview




Active smoking risk

Conclusions

Passive smoking

Secondhand smoke

Involuntary smoking











Acrylamide

Acrylonitrile

13-Butadiene

Isoprene

Nitromethane

Propylene Oxide


Vinyl chloride

4-Aminobiphenyl

Urethane

Benzene

Nitrobenzene

Benzo[a]pyrene

ortho-Toluidine

Dibenzo[ae]pyrene

Dibenzo[ai]pyrene

Dibenzo[al]pyrene






Mainstream Smoke

- Carbon monoxide

- Nitrogen Oxides

- Nicotine

25-15 times as much

37-128 times

13-21 as much

- Benzene

- Formaldehyde

- NNK

- Benz(a)pyrene

- Nickel

- Tar

8-10 times as much

50 times as much

1-22 times as much

25-20 times as much

13-30 times as much

11-157 times













01

1

10H

iray

am

a 199

2W

arte

nb

erg

et

al

200

0R

eyn

old

s e

t a

l 20

04

Ha

nao

ka e

t al

200

4S

an

dle

r e

t al 1

985

Millik

an

et

al 1

998

De

lfin

o e

t al

2000

Scru

bso

le e

t al

2004

Gam

mon

et a

l 200

4S

mit

h e

t al

1994

Mo

rab

ia e

t al 1

996

Zh

ao

et

al

1999

Jo

hn

so

n e

t al

200

0K

ro

pp

et

al

200

2L

isso

wsk

a e

t al 2

00

6M

issed

Ex

po

su

re -

Co

ho

rt

Stu

die

s

Mis

sed

Ex

po

su

re -

Cas

e-C

on

tro

l

Be

tte

r E

xp

osu

re

Asses

sm

en

t



|______________________________________|



|_____________________|

Cohort

|___________________________|

Case-control






















cancerrdquo



2005 1

Surgeon Generals

Report 20062


(95 CI)

N Relative Risk

(95 CI)

All studies 19 125 (108-144) 21 120 (108-135)

Premenopausal

Women lt 50

14 168 (131-215) 11 164 (125-214)

Premenopausal

with lifetime

exposure

assessment

5 220 (169-287) 6 185 (119-287)


Balancing Concerns








Ed



0

50

100

150

200

250

USA 1994

Europe 1998

Sweden 1998

Germany 1998

China 1999

Germany 2000

China 2000

Canada 2001

Excess Lung

Cancer Risk

(Percentage)


Higher Exposure

Work Only -

Higher Exposure


+1-25

+35-220 +50-210























Teachers Cohort[48]

Adjusted HR

(95 CI)

Womenrsquos Health


Adjusted HR (95

CI)


exposure

100 100







126 (099-160) 132(104-167)





























Exposure



40+ cigday

138 (105-183)

174 (115-262)



205 (120-349)


gt20 cigday 183 (129-261)


Initiation 10-14 146 (111-193)

148 (103-213)


(premeno) 39 (15-99)


Hanaoka et al 2004



Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)






Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)

Pooled

Analysis

Never

active

100 100 100 100

lt20 105 (086-128) 123 (103-146) 091 (072-116) 110 (089-135)

gt20 149 (108-204) 142 (116-174) 129 (089-186) 088 (069-113)






initiation

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137)

Al-Delaimy(2004) 129 (097-171)

Reynolds (2004) 117 (105-130)

Lawlor (2004)

Gram (2005) 148 (103-213)

Olson (2005) 112 (092-136)

Cui (2006) 111 (097-128)

Ha (2007) 148 (077-284)

8 of 8 positive

4 of 8 Stat Sig




initiation

Longest duration

before pregnancy

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131)

Al-Delaimy(2004) 129 (097-171) 110 (080-152)

Reynolds (2004) 117 (105-130) 113 (100-125)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137)

Olson (2005) 112 (092-136) 121 (101-125)

Cui (2006) 111 (097-128) 113 (101-125)

Ha (2007) 148 (077-284) 178 (127-249)11

9 of 9 positive

4 of 9 Stat Sig




initiation

Longest duration

before pregnancy

Longest

duration

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189)

Ha (2007) 148 (077-284) 178 (127-249)11

6 of 6 positive

3 of 6 Stat Sig




initiation

Longest duration

Before pregnancy

Longest

duration

Highest pack-

years

Calle (1994) 159 (117-215) 138 (105-183)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133) 125 (106-147)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174) 146 (111-193)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138) 115 (096-137)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189) 117 (102-134)

Ha (2007) 148 (077-284) 178 (127-249)11


5 of 5 positive




First Author Year



Relative Risk

(95 CI)

Reynolds et al (2004) lt20 117 (105-130)

Olson et al (2005) lt19 112 (092-136)

Xue et al (2011) lt18 104 (099-111)

Cui et al (2006) lt16 111 (097-128)


Gram et al (2005) lt15 148 (103-213)

Ha et al (2007) lt15 148 (077-284)



















i
























bull History

bull Lung diseases


bull History

bull Lung disease



TOBACCO SMOKE








INFLAMMATION



LUNG CANCER




ndash COPD

ndash Lung cancer









times








bull History

bull Lung disease












bull History

bull Lung diseases

bull COPD









bull Findings






bull Interpretation







Follow up (y)

Po

stb

ron

cho

dila

tor

FEV

1 L

24

25

26

27

28

29

Screen 2 1 2 3 4 5

Sustained Quitters

Continuous Smokers



COPD










bull Asthma

Asthma








32 subjects


10 quit smoking

Lung cancer













200615517-523















Wen et al--2010




Kolappan Gopi--2002

Thank you




Cancer


Lung

Mouth and pharynx

Larynx

Esophagus

Stomach

Pancreas

Liver

Cervix

Bladder

Kidney

Colorectum

Breast




Body mass index






45-74 years







history from women




51 of the cohort




Heavy smokers (12)


Light smokers (88)





Men (n=27292) Women (n=34028)


Percent 422 214 364 913 25 62


Lung cancer


Never 100

1-12 432 (355-523)

13-22 661 (546-802)

23+ 949 (758-1188)

P for trend lt00001

Smoking status

Lung cancer

RR (95 CI)

Never 100

Former 224 (181-278)

Current 585 (499-687)







Body Mass

Index (kgm2)

Never

smokers

Former

smokers

Current

smokers

Adj HR

(95 CI)

Adj HR

(95 CI)

Adj HR

(95 CI)

lt20 100 100 100

20-lt24 102 (071-146) 092 (057-148) 081 (067-099)

24-lt28 072 (046-110) 101 (059-174) 062 (046-082)

28+ 081 (046-144) 097 (044-212) 050 (028-088)

P for trend 008 089 00001



Smoking

status



Never 100 100 100 100

Former 246

(140-432)

197

(148-262)

296

(184-476)

199

(088-452)

Current 721

(484-1075)

520

(422-641)

550

(364-832)

321

(158-651)





1-12 618

(398-958)

365

(282-473)

365

(212-628)

290

(115-727)

13-22 792

(501-1253)

639

(498-820)

541

(323-905)

221

(071-686)

23+ 1112

(660-1870)

853

(635-1150)

901

(504-1610)

637

(210-1930)

P trend lt00001 lt00001 lt00001 00001




of lung cancer





damage





weights



developed world



Obesity

Western diet

Physical inactivity

Smoking







GST enzymes







GSTP1 polymorphism







Smokers














us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang













Greece

Italy

Spain





Community Medicine

Faculty of Medicine


March 23 2012


Singapore

Overview




Active smoking risk

Conclusions

Passive smoking

Secondhand smoke

Involuntary smoking











Acrylamide

Acrylonitrile

13-Butadiene

Isoprene

Nitromethane

Propylene Oxide


Vinyl chloride

4-Aminobiphenyl

Urethane

Benzene

Nitrobenzene

Benzo[a]pyrene

ortho-Toluidine

Dibenzo[ae]pyrene

Dibenzo[ai]pyrene

Dibenzo[al]pyrene






Mainstream Smoke

- Carbon monoxide

- Nitrogen Oxides

- Nicotine

25-15 times as much

37-128 times

13-21 as much

- Benzene

- Formaldehyde

- NNK

- Benz(a)pyrene

- Nickel

- Tar

8-10 times as much

50 times as much

1-22 times as much

25-20 times as much

13-30 times as much

11-157 times













01

1

10H

iray

am

a 199

2W

arte

nb

erg

et

al

200

0R

eyn

old

s e

t a

l 20

04

Ha

nao

ka e

t al

200

4S

an

dle

r e

t al 1

985

Millik

an

et

al 1

998

De

lfin

o e

t al

2000

Scru

bso

le e

t al

2004

Gam

mon

et a

l 200

4S

mit

h e

t al

1994

Mo

rab

ia e

t al 1

996

Zh

ao

et

al

1999

Jo

hn

so

n e

t al

200

0K

ro

pp

et

al

200

2L

isso

wsk

a e

t al 2

00

6M

issed

Ex

po

su

re -

Co

ho

rt

Stu

die

s

Mis

sed

Ex

po

su

re -

Cas

e-C

on

tro

l

Be

tte

r E

xp

osu

re

Asses

sm

en

t



|______________________________________|



|_____________________|

Cohort

|___________________________|

Case-control






















cancerrdquo



2005 1

Surgeon Generals

Report 20062


(95 CI)

N Relative Risk

(95 CI)

All studies 19 125 (108-144) 21 120 (108-135)

Premenopausal

Women lt 50

14 168 (131-215) 11 164 (125-214)

Premenopausal

with lifetime

exposure

assessment

5 220 (169-287) 6 185 (119-287)


Balancing Concerns








Ed



0

50

100

150

200

250

USA 1994

Europe 1998

Sweden 1998

Germany 1998

China 1999

Germany 2000

China 2000

Canada 2001

Excess Lung

Cancer Risk

(Percentage)


Higher Exposure

Work Only -

Higher Exposure


+1-25

+35-220 +50-210























Teachers Cohort[48]

Adjusted HR

(95 CI)

Womenrsquos Health


Adjusted HR (95

CI)


exposure

100 100







126 (099-160) 132(104-167)





























Exposure



40+ cigday

138 (105-183)

174 (115-262)



205 (120-349)


gt20 cigday 183 (129-261)


Initiation 10-14 146 (111-193)

148 (103-213)


(premeno) 39 (15-99)


Hanaoka et al 2004



Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)






Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)

Pooled

Analysis

Never

active

100 100 100 100

lt20 105 (086-128) 123 (103-146) 091 (072-116) 110 (089-135)

gt20 149 (108-204) 142 (116-174) 129 (089-186) 088 (069-113)






initiation

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137)

Al-Delaimy(2004) 129 (097-171)

Reynolds (2004) 117 (105-130)

Lawlor (2004)

Gram (2005) 148 (103-213)

Olson (2005) 112 (092-136)

Cui (2006) 111 (097-128)

Ha (2007) 148 (077-284)

8 of 8 positive

4 of 8 Stat Sig




initiation

Longest duration

before pregnancy

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131)

Al-Delaimy(2004) 129 (097-171) 110 (080-152)

Reynolds (2004) 117 (105-130) 113 (100-125)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137)

Olson (2005) 112 (092-136) 121 (101-125)

Cui (2006) 111 (097-128) 113 (101-125)

Ha (2007) 148 (077-284) 178 (127-249)11

9 of 9 positive

4 of 9 Stat Sig




initiation

Longest duration

before pregnancy

Longest

duration

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189)

Ha (2007) 148 (077-284) 178 (127-249)11

6 of 6 positive

3 of 6 Stat Sig




initiation

Longest duration

Before pregnancy

Longest

duration

Highest pack-

years

Calle (1994) 159 (117-215) 138 (105-183)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133) 125 (106-147)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174) 146 (111-193)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138) 115 (096-137)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189) 117 (102-134)

Ha (2007) 148 (077-284) 178 (127-249)11


5 of 5 positive




First Author Year



Relative Risk

(95 CI)

Reynolds et al (2004) lt20 117 (105-130)

Olson et al (2005) lt19 112 (092-136)

Xue et al (2011) lt18 104 (099-111)

Cui et al (2006) lt16 111 (097-128)


Gram et al (2005) lt15 148 (103-213)

Ha et al (2007) lt15 148 (077-284)



















i
























bull History

bull Lung diseases


bull History

bull Lung disease



TOBACCO SMOKE








INFLAMMATION



LUNG CANCER




ndash COPD

ndash Lung cancer









times








bull History

bull Lung disease












bull History

bull Lung diseases

bull COPD









bull Findings






bull Interpretation







Follow up (y)

Po

stb

ron

cho

dila

tor

FEV

1 L

24

25

26

27

28

29

Screen 2 1 2 3 4 5

Sustained Quitters

Continuous Smokers



COPD










bull Asthma

Asthma








32 subjects


10 quit smoking

Lung cancer













200615517-523















Wen et al--2010




Kolappan Gopi--2002

Thank you




Cancer


Lung

Mouth and pharynx

Larynx

Esophagus

Stomach

Pancreas

Liver

Cervix

Bladder

Kidney

Colorectum

Breast




Body mass index






45-74 years







history from women




51 of the cohort




Heavy smokers (12)


Light smokers (88)





Men (n=27292) Women (n=34028)


Percent 422 214 364 913 25 62


Lung cancer


Never 100

1-12 432 (355-523)

13-22 661 (546-802)

23+ 949 (758-1188)

P for trend lt00001

Smoking status

Lung cancer

RR (95 CI)

Never 100

Former 224 (181-278)

Current 585 (499-687)







Body Mass

Index (kgm2)

Never

smokers

Former

smokers

Current

smokers

Adj HR

(95 CI)

Adj HR

(95 CI)

Adj HR

(95 CI)

lt20 100 100 100

20-lt24 102 (071-146) 092 (057-148) 081 (067-099)

24-lt28 072 (046-110) 101 (059-174) 062 (046-082)

28+ 081 (046-144) 097 (044-212) 050 (028-088)

P for trend 008 089 00001



Smoking

status



Never 100 100 100 100

Former 246

(140-432)

197

(148-262)

296

(184-476)

199

(088-452)

Current 721

(484-1075)

520

(422-641)

550

(364-832)

321

(158-651)





1-12 618

(398-958)

365

(282-473)

365

(212-628)

290

(115-727)

13-22 792

(501-1253)

639

(498-820)

541

(323-905)

221

(071-686)

23+ 1112

(660-1870)

853

(635-1150)

901

(504-1610)

637

(210-1930)

P trend lt00001 lt00001 lt00001 00001




of lung cancer





damage





weights



developed world



Obesity

Western diet

Physical inactivity

Smoking







GST enzymes







GSTP1 polymorphism







Smokers














us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang











Community Medicine

Faculty of Medicine


March 23 2012


Singapore

Overview




Active smoking risk

Conclusions

Passive smoking

Secondhand smoke

Involuntary smoking











Acrylamide

Acrylonitrile

13-Butadiene

Isoprene

Nitromethane

Propylene Oxide


Vinyl chloride

4-Aminobiphenyl

Urethane

Benzene

Nitrobenzene

Benzo[a]pyrene

ortho-Toluidine

Dibenzo[ae]pyrene

Dibenzo[ai]pyrene

Dibenzo[al]pyrene






Mainstream Smoke

- Carbon monoxide

- Nitrogen Oxides

- Nicotine

25-15 times as much

37-128 times

13-21 as much

- Benzene

- Formaldehyde

- NNK

- Benz(a)pyrene

- Nickel

- Tar

8-10 times as much

50 times as much

1-22 times as much

25-20 times as much

13-30 times as much

11-157 times













01

1

10H

iray

am

a 199

2W

arte

nb

erg

et

al

200

0R

eyn

old

s e

t a

l 20

04

Ha

nao

ka e

t al

200

4S

an

dle

r e

t al 1

985

Millik

an

et

al 1

998

De

lfin

o e

t al

2000

Scru

bso

le e

t al

2004

Gam

mon

et a

l 200

4S

mit

h e

t al

1994

Mo

rab

ia e

t al 1

996

Zh

ao

et

al

1999

Jo

hn

so

n e

t al

200

0K

ro

pp

et

al

200

2L

isso

wsk

a e

t al 2

00

6M

issed

Ex

po

su

re -

Co

ho

rt

Stu

die

s

Mis

sed

Ex

po

su

re -

Cas

e-C

on

tro

l

Be

tte

r E

xp

osu

re

Asses

sm

en

t



|______________________________________|



|_____________________|

Cohort

|___________________________|

Case-control






















cancerrdquo



2005 1

Surgeon Generals

Report 20062


(95 CI)

N Relative Risk

(95 CI)

All studies 19 125 (108-144) 21 120 (108-135)

Premenopausal

Women lt 50

14 168 (131-215) 11 164 (125-214)

Premenopausal

with lifetime

exposure

assessment

5 220 (169-287) 6 185 (119-287)


Balancing Concerns








Ed



0

50

100

150

200

250

USA 1994

Europe 1998

Sweden 1998

Germany 1998

China 1999

Germany 2000

China 2000

Canada 2001

Excess Lung

Cancer Risk

(Percentage)


Higher Exposure

Work Only -

Higher Exposure


+1-25

+35-220 +50-210























Teachers Cohort[48]

Adjusted HR

(95 CI)

Womenrsquos Health


Adjusted HR (95

CI)


exposure

100 100







126 (099-160) 132(104-167)





























Exposure



40+ cigday

138 (105-183)

174 (115-262)



205 (120-349)


gt20 cigday 183 (129-261)


Initiation 10-14 146 (111-193)

148 (103-213)


(premeno) 39 (15-99)


Hanaoka et al 2004



Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)






Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)

Pooled

Analysis

Never

active

100 100 100 100

lt20 105 (086-128) 123 (103-146) 091 (072-116) 110 (089-135)

gt20 149 (108-204) 142 (116-174) 129 (089-186) 088 (069-113)






initiation

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137)

Al-Delaimy(2004) 129 (097-171)

Reynolds (2004) 117 (105-130)

Lawlor (2004)

Gram (2005) 148 (103-213)

Olson (2005) 112 (092-136)

Cui (2006) 111 (097-128)

Ha (2007) 148 (077-284)

8 of 8 positive

4 of 8 Stat Sig




initiation

Longest duration

before pregnancy

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131)

Al-Delaimy(2004) 129 (097-171) 110 (080-152)

Reynolds (2004) 117 (105-130) 113 (100-125)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137)

Olson (2005) 112 (092-136) 121 (101-125)

Cui (2006) 111 (097-128) 113 (101-125)

Ha (2007) 148 (077-284) 178 (127-249)11

9 of 9 positive

4 of 9 Stat Sig




initiation

Longest duration

before pregnancy

Longest

duration

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189)

Ha (2007) 148 (077-284) 178 (127-249)11

6 of 6 positive

3 of 6 Stat Sig




initiation

Longest duration

Before pregnancy

Longest

duration

Highest pack-

years

Calle (1994) 159 (117-215) 138 (105-183)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133) 125 (106-147)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174) 146 (111-193)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138) 115 (096-137)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189) 117 (102-134)

Ha (2007) 148 (077-284) 178 (127-249)11


5 of 5 positive




First Author Year



Relative Risk

(95 CI)

Reynolds et al (2004) lt20 117 (105-130)

Olson et al (2005) lt19 112 (092-136)

Xue et al (2011) lt18 104 (099-111)

Cui et al (2006) lt16 111 (097-128)


Gram et al (2005) lt15 148 (103-213)

Ha et al (2007) lt15 148 (077-284)



















i
























bull History

bull Lung diseases


bull History

bull Lung disease



TOBACCO SMOKE








INFLAMMATION



LUNG CANCER




ndash COPD

ndash Lung cancer









times








bull History

bull Lung disease












bull History

bull Lung diseases

bull COPD









bull Findings






bull Interpretation







Follow up (y)

Po

stb

ron

cho

dila

tor

FEV

1 L

24

25

26

27

28

29

Screen 2 1 2 3 4 5

Sustained Quitters

Continuous Smokers



COPD










bull Asthma

Asthma








32 subjects


10 quit smoking

Lung cancer













200615517-523















Wen et al--2010




Kolappan Gopi--2002

Thank you




Cancer


Lung

Mouth and pharynx

Larynx

Esophagus

Stomach

Pancreas

Liver

Cervix

Bladder

Kidney

Colorectum

Breast




Body mass index






45-74 years







history from women




51 of the cohort




Heavy smokers (12)


Light smokers (88)





Men (n=27292) Women (n=34028)


Percent 422 214 364 913 25 62


Lung cancer


Never 100

1-12 432 (355-523)

13-22 661 (546-802)

23+ 949 (758-1188)

P for trend lt00001

Smoking status

Lung cancer

RR (95 CI)

Never 100

Former 224 (181-278)

Current 585 (499-687)







Body Mass

Index (kgm2)

Never

smokers

Former

smokers

Current

smokers

Adj HR

(95 CI)

Adj HR

(95 CI)

Adj HR

(95 CI)

lt20 100 100 100

20-lt24 102 (071-146) 092 (057-148) 081 (067-099)

24-lt28 072 (046-110) 101 (059-174) 062 (046-082)

28+ 081 (046-144) 097 (044-212) 050 (028-088)

P for trend 008 089 00001



Smoking

status



Never 100 100 100 100

Former 246

(140-432)

197

(148-262)

296

(184-476)

199

(088-452)

Current 721

(484-1075)

520

(422-641)

550

(364-832)

321

(158-651)





1-12 618

(398-958)

365

(282-473)

365

(212-628)

290

(115-727)

13-22 792

(501-1253)

639

(498-820)

541

(323-905)

221

(071-686)

23+ 1112

(660-1870)

853

(635-1150)

901

(504-1610)

637

(210-1930)

P trend lt00001 lt00001 lt00001 00001




of lung cancer





damage





weights



developed world



Obesity

Western diet

Physical inactivity

Smoking







GST enzymes







GSTP1 polymorphism







Smokers














us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang







Overview




Active smoking risk

Conclusions

Passive smoking

Secondhand smoke

Involuntary smoking











Acrylamide

Acrylonitrile

13-Butadiene

Isoprene

Nitromethane

Propylene Oxide


Vinyl chloride

4-Aminobiphenyl

Urethane

Benzene

Nitrobenzene

Benzo[a]pyrene

ortho-Toluidine

Dibenzo[ae]pyrene

Dibenzo[ai]pyrene

Dibenzo[al]pyrene






Mainstream Smoke

- Carbon monoxide

- Nitrogen Oxides

- Nicotine

25-15 times as much

37-128 times

13-21 as much

- Benzene

- Formaldehyde

- NNK

- Benz(a)pyrene

- Nickel

- Tar

8-10 times as much

50 times as much

1-22 times as much

25-20 times as much

13-30 times as much

11-157 times













01

1

10H

iray

am

a 199

2W

arte

nb

erg

et

al

200

0R

eyn

old

s e

t a

l 20

04

Ha

nao

ka e

t al

200

4S

an

dle

r e

t al 1

985

Millik

an

et

al 1

998

De

lfin

o e

t al

2000

Scru

bso

le e

t al

2004

Gam

mon

et a

l 200

4S

mit

h e

t al

1994

Mo

rab

ia e

t al 1

996

Zh

ao

et

al

1999

Jo

hn

so

n e

t al

200

0K

ro

pp

et

al

200

2L

isso

wsk

a e

t al 2

00

6M

issed

Ex

po

su

re -

Co

ho

rt

Stu

die

s

Mis

sed

Ex

po

su

re -

Cas

e-C

on

tro

l

Be

tte

r E

xp

osu

re

Asses

sm

en

t



|______________________________________|



|_____________________|

Cohort

|___________________________|

Case-control






















cancerrdquo



2005 1

Surgeon Generals

Report 20062


(95 CI)

N Relative Risk

(95 CI)

All studies 19 125 (108-144) 21 120 (108-135)

Premenopausal

Women lt 50

14 168 (131-215) 11 164 (125-214)

Premenopausal

with lifetime

exposure

assessment

5 220 (169-287) 6 185 (119-287)


Balancing Concerns








Ed



0

50

100

150

200

250

USA 1994

Europe 1998

Sweden 1998

Germany 1998

China 1999

Germany 2000

China 2000

Canada 2001

Excess Lung

Cancer Risk

(Percentage)


Higher Exposure

Work Only -

Higher Exposure


+1-25

+35-220 +50-210























Teachers Cohort[48]

Adjusted HR

(95 CI)

Womenrsquos Health


Adjusted HR (95

CI)


exposure

100 100







126 (099-160) 132(104-167)





























Exposure



40+ cigday

138 (105-183)

174 (115-262)



205 (120-349)


gt20 cigday 183 (129-261)


Initiation 10-14 146 (111-193)

148 (103-213)


(premeno) 39 (15-99)


Hanaoka et al 2004



Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)






Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)

Pooled

Analysis

Never

active

100 100 100 100

lt20 105 (086-128) 123 (103-146) 091 (072-116) 110 (089-135)

gt20 149 (108-204) 142 (116-174) 129 (089-186) 088 (069-113)






initiation

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137)

Al-Delaimy(2004) 129 (097-171)

Reynolds (2004) 117 (105-130)

Lawlor (2004)

Gram (2005) 148 (103-213)

Olson (2005) 112 (092-136)

Cui (2006) 111 (097-128)

Ha (2007) 148 (077-284)

8 of 8 positive

4 of 8 Stat Sig




initiation

Longest duration

before pregnancy

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131)

Al-Delaimy(2004) 129 (097-171) 110 (080-152)

Reynolds (2004) 117 (105-130) 113 (100-125)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137)

Olson (2005) 112 (092-136) 121 (101-125)

Cui (2006) 111 (097-128) 113 (101-125)

Ha (2007) 148 (077-284) 178 (127-249)11

9 of 9 positive

4 of 9 Stat Sig




initiation

Longest duration

before pregnancy

Longest

duration

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189)

Ha (2007) 148 (077-284) 178 (127-249)11

6 of 6 positive

3 of 6 Stat Sig




initiation

Longest duration

Before pregnancy

Longest

duration

Highest pack-

years

Calle (1994) 159 (117-215) 138 (105-183)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133) 125 (106-147)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174) 146 (111-193)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138) 115 (096-137)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189) 117 (102-134)

Ha (2007) 148 (077-284) 178 (127-249)11


5 of 5 positive




First Author Year



Relative Risk

(95 CI)

Reynolds et al (2004) lt20 117 (105-130)

Olson et al (2005) lt19 112 (092-136)

Xue et al (2011) lt18 104 (099-111)

Cui et al (2006) lt16 111 (097-128)


Gram et al (2005) lt15 148 (103-213)

Ha et al (2007) lt15 148 (077-284)



















i
























bull History

bull Lung diseases


bull History

bull Lung disease



TOBACCO SMOKE








INFLAMMATION



LUNG CANCER




ndash COPD

ndash Lung cancer









times








bull History

bull Lung disease












bull History

bull Lung diseases

bull COPD









bull Findings






bull Interpretation







Follow up (y)

Po

stb

ron

cho

dila

tor

FEV

1 L

24

25

26

27

28

29

Screen 2 1 2 3 4 5

Sustained Quitters

Continuous Smokers



COPD










bull Asthma

Asthma








32 subjects


10 quit smoking

Lung cancer













200615517-523















Wen et al--2010




Kolappan Gopi--2002

Thank you




Cancer


Lung

Mouth and pharynx

Larynx

Esophagus

Stomach

Pancreas

Liver

Cervix

Bladder

Kidney

Colorectum

Breast




Body mass index






45-74 years







history from women




51 of the cohort




Heavy smokers (12)


Light smokers (88)





Men (n=27292) Women (n=34028)


Percent 422 214 364 913 25 62


Lung cancer


Never 100

1-12 432 (355-523)

13-22 661 (546-802)

23+ 949 (758-1188)

P for trend lt00001

Smoking status

Lung cancer

RR (95 CI)

Never 100

Former 224 (181-278)

Current 585 (499-687)







Body Mass

Index (kgm2)

Never

smokers

Former

smokers

Current

smokers

Adj HR

(95 CI)

Adj HR

(95 CI)

Adj HR

(95 CI)

lt20 100 100 100

20-lt24 102 (071-146) 092 (057-148) 081 (067-099)

24-lt28 072 (046-110) 101 (059-174) 062 (046-082)

28+ 081 (046-144) 097 (044-212) 050 (028-088)

P for trend 008 089 00001



Smoking

status



Never 100 100 100 100

Former 246

(140-432)

197

(148-262)

296

(184-476)

199

(088-452)

Current 721

(484-1075)

520

(422-641)

550

(364-832)

321

(158-651)





1-12 618

(398-958)

365

(282-473)

365

(212-628)

290

(115-727)

13-22 792

(501-1253)

639

(498-820)

541

(323-905)

221

(071-686)

23+ 1112

(660-1870)

853

(635-1150)

901

(504-1610)

637

(210-1930)

P trend lt00001 lt00001 lt00001 00001




of lung cancer





damage





weights



developed world



Obesity

Western diet

Physical inactivity

Smoking







GST enzymes







GSTP1 polymorphism







Smokers














us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang







Passive smoking

Secondhand smoke

Involuntary smoking











Acrylamide

Acrylonitrile

13-Butadiene

Isoprene

Nitromethane

Propylene Oxide


Vinyl chloride

4-Aminobiphenyl

Urethane

Benzene

Nitrobenzene

Benzo[a]pyrene

ortho-Toluidine

Dibenzo[ae]pyrene

Dibenzo[ai]pyrene

Dibenzo[al]pyrene






Mainstream Smoke

- Carbon monoxide

- Nitrogen Oxides

- Nicotine

25-15 times as much

37-128 times

13-21 as much

- Benzene

- Formaldehyde

- NNK

- Benz(a)pyrene

- Nickel

- Tar

8-10 times as much

50 times as much

1-22 times as much

25-20 times as much

13-30 times as much

11-157 times













01

1

10H

iray

am

a 199

2W

arte

nb

erg

et

al

200

0R

eyn

old

s e

t a

l 20

04

Ha

nao

ka e

t al

200

4S

an

dle

r e

t al 1

985

Millik

an

et

al 1

998

De

lfin

o e

t al

2000

Scru

bso

le e

t al

2004

Gam

mon

et a

l 200

4S

mit

h e

t al

1994

Mo

rab

ia e

t al 1

996

Zh

ao

et

al

1999

Jo

hn

so

n e

t al

200

0K

ro

pp

et

al

200

2L

isso

wsk

a e

t al 2

00

6M

issed

Ex

po

su

re -

Co

ho

rt

Stu

die

s

Mis

sed

Ex

po

su

re -

Cas

e-C

on

tro

l

Be

tte

r E

xp

osu

re

Asses

sm

en

t



|______________________________________|



|_____________________|

Cohort

|___________________________|

Case-control






















cancerrdquo



2005 1

Surgeon Generals

Report 20062


(95 CI)

N Relative Risk

(95 CI)

All studies 19 125 (108-144) 21 120 (108-135)

Premenopausal

Women lt 50

14 168 (131-215) 11 164 (125-214)

Premenopausal

with lifetime

exposure

assessment

5 220 (169-287) 6 185 (119-287)


Balancing Concerns








Ed



0

50

100

150

200

250

USA 1994

Europe 1998

Sweden 1998

Germany 1998

China 1999

Germany 2000

China 2000

Canada 2001

Excess Lung

Cancer Risk

(Percentage)


Higher Exposure

Work Only -

Higher Exposure


+1-25

+35-220 +50-210























Teachers Cohort[48]

Adjusted HR

(95 CI)

Womenrsquos Health


Adjusted HR (95

CI)


exposure

100 100







126 (099-160) 132(104-167)





























Exposure



40+ cigday

138 (105-183)

174 (115-262)



205 (120-349)


gt20 cigday 183 (129-261)


Initiation 10-14 146 (111-193)

148 (103-213)


(premeno) 39 (15-99)


Hanaoka et al 2004



Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)






Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)

Pooled

Analysis

Never

active

100 100 100 100

lt20 105 (086-128) 123 (103-146) 091 (072-116) 110 (089-135)

gt20 149 (108-204) 142 (116-174) 129 (089-186) 088 (069-113)






initiation

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137)

Al-Delaimy(2004) 129 (097-171)

Reynolds (2004) 117 (105-130)

Lawlor (2004)

Gram (2005) 148 (103-213)

Olson (2005) 112 (092-136)

Cui (2006) 111 (097-128)

Ha (2007) 148 (077-284)

8 of 8 positive

4 of 8 Stat Sig




initiation

Longest duration

before pregnancy

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131)

Al-Delaimy(2004) 129 (097-171) 110 (080-152)

Reynolds (2004) 117 (105-130) 113 (100-125)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137)

Olson (2005) 112 (092-136) 121 (101-125)

Cui (2006) 111 (097-128) 113 (101-125)

Ha (2007) 148 (077-284) 178 (127-249)11

9 of 9 positive

4 of 9 Stat Sig




initiation

Longest duration

before pregnancy

Longest

duration

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189)

Ha (2007) 148 (077-284) 178 (127-249)11

6 of 6 positive

3 of 6 Stat Sig




initiation

Longest duration

Before pregnancy

Longest

duration

Highest pack-

years

Calle (1994) 159 (117-215) 138 (105-183)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133) 125 (106-147)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174) 146 (111-193)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138) 115 (096-137)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189) 117 (102-134)

Ha (2007) 148 (077-284) 178 (127-249)11


5 of 5 positive




First Author Year



Relative Risk

(95 CI)

Reynolds et al (2004) lt20 117 (105-130)

Olson et al (2005) lt19 112 (092-136)

Xue et al (2011) lt18 104 (099-111)

Cui et al (2006) lt16 111 (097-128)


Gram et al (2005) lt15 148 (103-213)

Ha et al (2007) lt15 148 (077-284)



















i
























bull History

bull Lung diseases


bull History

bull Lung disease



TOBACCO SMOKE








INFLAMMATION



LUNG CANCER




ndash COPD

ndash Lung cancer









times








bull History

bull Lung disease












bull History

bull Lung diseases

bull COPD









bull Findings






bull Interpretation







Follow up (y)

Po

stb

ron

cho

dila

tor

FEV

1 L

24

25

26

27

28

29

Screen 2 1 2 3 4 5

Sustained Quitters

Continuous Smokers



COPD










bull Asthma

Asthma








32 subjects


10 quit smoking

Lung cancer













200615517-523















Wen et al--2010




Kolappan Gopi--2002

Thank you




Cancer


Lung

Mouth and pharynx

Larynx

Esophagus

Stomach

Pancreas

Liver

Cervix

Bladder

Kidney

Colorectum

Breast




Body mass index






45-74 years







history from women




51 of the cohort




Heavy smokers (12)


Light smokers (88)





Men (n=27292) Women (n=34028)


Percent 422 214 364 913 25 62


Lung cancer


Never 100

1-12 432 (355-523)

13-22 661 (546-802)

23+ 949 (758-1188)

P for trend lt00001

Smoking status

Lung cancer

RR (95 CI)

Never 100

Former 224 (181-278)

Current 585 (499-687)







Body Mass

Index (kgm2)

Never

smokers

Former

smokers

Current

smokers

Adj HR

(95 CI)

Adj HR

(95 CI)

Adj HR

(95 CI)

lt20 100 100 100

20-lt24 102 (071-146) 092 (057-148) 081 (067-099)

24-lt28 072 (046-110) 101 (059-174) 062 (046-082)

28+ 081 (046-144) 097 (044-212) 050 (028-088)

P for trend 008 089 00001



Smoking

status



Never 100 100 100 100

Former 246

(140-432)

197

(148-262)

296

(184-476)

199

(088-452)

Current 721

(484-1075)

520

(422-641)

550

(364-832)

321

(158-651)





1-12 618

(398-958)

365

(282-473)

365

(212-628)

290

(115-727)

13-22 792

(501-1253)

639

(498-820)

541

(323-905)

221

(071-686)

23+ 1112

(660-1870)

853

(635-1150)

901

(504-1610)

637

(210-1930)

P trend lt00001 lt00001 lt00001 00001




of lung cancer





damage





weights



developed world



Obesity

Western diet

Physical inactivity

Smoking







GST enzymes







GSTP1 polymorphism







Smokers














us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang
















Acrylamide

Acrylonitrile

13-Butadiene

Isoprene

Nitromethane

Propylene Oxide


Vinyl chloride

4-Aminobiphenyl

Urethane

Benzene

Nitrobenzene

Benzo[a]pyrene

ortho-Toluidine

Dibenzo[ae]pyrene

Dibenzo[ai]pyrene

Dibenzo[al]pyrene






Mainstream Smoke

- Carbon monoxide

- Nitrogen Oxides

- Nicotine

25-15 times as much

37-128 times

13-21 as much

- Benzene

- Formaldehyde

- NNK

- Benz(a)pyrene

- Nickel

- Tar

8-10 times as much

50 times as much

1-22 times as much

25-20 times as much

13-30 times as much

11-157 times













01

1

10H

iray

am

a 199

2W

arte

nb

erg

et

al

200

0R

eyn

old

s e

t a

l 20

04

Ha

nao

ka e

t al

200

4S

an

dle

r e

t al 1

985

Millik

an

et

al 1

998

De

lfin

o e

t al

2000

Scru

bso

le e

t al

2004

Gam

mon

et a

l 200

4S

mit

h e

t al

1994

Mo

rab

ia e

t al 1

996

Zh

ao

et

al

1999

Jo

hn

so

n e

t al

200

0K

ro

pp

et

al

200

2L

isso

wsk

a e

t al 2

00

6M

issed

Ex

po

su

re -

Co

ho

rt

Stu

die

s

Mis

sed

Ex

po

su

re -

Cas

e-C

on

tro

l

Be

tte

r E

xp

osu

re

Asses

sm

en

t



|______________________________________|



|_____________________|

Cohort

|___________________________|

Case-control






















cancerrdquo



2005 1

Surgeon Generals

Report 20062


(95 CI)

N Relative Risk

(95 CI)

All studies 19 125 (108-144) 21 120 (108-135)

Premenopausal

Women lt 50

14 168 (131-215) 11 164 (125-214)

Premenopausal

with lifetime

exposure

assessment

5 220 (169-287) 6 185 (119-287)


Balancing Concerns








Ed



0

50

100

150

200

250

USA 1994

Europe 1998

Sweden 1998

Germany 1998

China 1999

Germany 2000

China 2000

Canada 2001

Excess Lung

Cancer Risk

(Percentage)


Higher Exposure

Work Only -

Higher Exposure


+1-25

+35-220 +50-210























Teachers Cohort[48]

Adjusted HR

(95 CI)

Womenrsquos Health


Adjusted HR (95

CI)


exposure

100 100







126 (099-160) 132(104-167)





























Exposure



40+ cigday

138 (105-183)

174 (115-262)



205 (120-349)


gt20 cigday 183 (129-261)


Initiation 10-14 146 (111-193)

148 (103-213)


(premeno) 39 (15-99)


Hanaoka et al 2004



Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)






Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)

Pooled

Analysis

Never

active

100 100 100 100

lt20 105 (086-128) 123 (103-146) 091 (072-116) 110 (089-135)

gt20 149 (108-204) 142 (116-174) 129 (089-186) 088 (069-113)






initiation

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137)

Al-Delaimy(2004) 129 (097-171)

Reynolds (2004) 117 (105-130)

Lawlor (2004)

Gram (2005) 148 (103-213)

Olson (2005) 112 (092-136)

Cui (2006) 111 (097-128)

Ha (2007) 148 (077-284)

8 of 8 positive

4 of 8 Stat Sig




initiation

Longest duration

before pregnancy

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131)

Al-Delaimy(2004) 129 (097-171) 110 (080-152)

Reynolds (2004) 117 (105-130) 113 (100-125)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137)

Olson (2005) 112 (092-136) 121 (101-125)

Cui (2006) 111 (097-128) 113 (101-125)

Ha (2007) 148 (077-284) 178 (127-249)11

9 of 9 positive

4 of 9 Stat Sig




initiation

Longest duration

before pregnancy

Longest

duration

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189)

Ha (2007) 148 (077-284) 178 (127-249)11

6 of 6 positive

3 of 6 Stat Sig




initiation

Longest duration

Before pregnancy

Longest

duration

Highest pack-

years

Calle (1994) 159 (117-215) 138 (105-183)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133) 125 (106-147)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174) 146 (111-193)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138) 115 (096-137)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189) 117 (102-134)

Ha (2007) 148 (077-284) 178 (127-249)11


5 of 5 positive




First Author Year



Relative Risk

(95 CI)

Reynolds et al (2004) lt20 117 (105-130)

Olson et al (2005) lt19 112 (092-136)

Xue et al (2011) lt18 104 (099-111)

Cui et al (2006) lt16 111 (097-128)


Gram et al (2005) lt15 148 (103-213)

Ha et al (2007) lt15 148 (077-284)



















i
























bull History

bull Lung diseases


bull History

bull Lung disease



TOBACCO SMOKE








INFLAMMATION



LUNG CANCER




ndash COPD

ndash Lung cancer









times








bull History

bull Lung disease












bull History

bull Lung diseases

bull COPD









bull Findings






bull Interpretation







Follow up (y)

Po

stb

ron

cho

dila

tor

FEV

1 L

24

25

26

27

28

29

Screen 2 1 2 3 4 5

Sustained Quitters

Continuous Smokers



COPD










bull Asthma

Asthma








32 subjects


10 quit smoking

Lung cancer













200615517-523















Wen et al--2010




Kolappan Gopi--2002

Thank you




Cancer


Lung

Mouth and pharynx

Larynx

Esophagus

Stomach

Pancreas

Liver

Cervix

Bladder

Kidney

Colorectum

Breast




Body mass index






45-74 years







history from women




51 of the cohort




Heavy smokers (12)


Light smokers (88)





Men (n=27292) Women (n=34028)


Percent 422 214 364 913 25 62


Lung cancer


Never 100

1-12 432 (355-523)

13-22 661 (546-802)

23+ 949 (758-1188)

P for trend lt00001

Smoking status

Lung cancer

RR (95 CI)

Never 100

Former 224 (181-278)

Current 585 (499-687)







Body Mass

Index (kgm2)

Never

smokers

Former

smokers

Current

smokers

Adj HR

(95 CI)

Adj HR

(95 CI)

Adj HR

(95 CI)

lt20 100 100 100

20-lt24 102 (071-146) 092 (057-148) 081 (067-099)

24-lt28 072 (046-110) 101 (059-174) 062 (046-082)

28+ 081 (046-144) 097 (044-212) 050 (028-088)

P for trend 008 089 00001



Smoking

status



Never 100 100 100 100

Former 246

(140-432)

197

(148-262)

296

(184-476)

199

(088-452)

Current 721

(484-1075)

520

(422-641)

550

(364-832)

321

(158-651)





1-12 618

(398-958)

365

(282-473)

365

(212-628)

290

(115-727)

13-22 792

(501-1253)

639

(498-820)

541

(323-905)

221

(071-686)

23+ 1112

(660-1870)

853

(635-1150)

901

(504-1610)

637

(210-1930)

P trend lt00001 lt00001 lt00001 00001




of lung cancer





damage





weights



developed world



Obesity

Western diet

Physical inactivity

Smoking







GST enzymes







GSTP1 polymorphism







Smokers














us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang










Mainstream Smoke

- Carbon monoxide

- Nitrogen Oxides

- Nicotine

25-15 times as much

37-128 times

13-21 as much

- Benzene

- Formaldehyde

- NNK

- Benz(a)pyrene

- Nickel

- Tar

8-10 times as much

50 times as much

1-22 times as much

25-20 times as much

13-30 times as much

11-157 times













01

1

10H

iray

am

a 199

2W

arte

nb

erg

et

al

200

0R

eyn

old

s e

t a

l 20

04

Ha

nao

ka e

t al

200

4S

an

dle

r e

t al 1

985

Millik

an

et

al 1

998

De

lfin

o e

t al

2000

Scru

bso

le e

t al

2004

Gam

mon

et a

l 200

4S

mit

h e

t al

1994

Mo

rab

ia e

t al 1

996

Zh

ao

et

al

1999

Jo

hn

so

n e

t al

200

0K

ro

pp

et

al

200

2L

isso

wsk

a e

t al 2

00

6M

issed

Ex

po

su

re -

Co

ho

rt

Stu

die

s

Mis

sed

Ex

po

su

re -

Cas

e-C

on

tro

l

Be

tte

r E

xp

osu

re

Asses

sm

en

t



|______________________________________|



|_____________________|

Cohort

|___________________________|

Case-control






















cancerrdquo



2005 1

Surgeon Generals

Report 20062


(95 CI)

N Relative Risk

(95 CI)

All studies 19 125 (108-144) 21 120 (108-135)

Premenopausal

Women lt 50

14 168 (131-215) 11 164 (125-214)

Premenopausal

with lifetime

exposure

assessment

5 220 (169-287) 6 185 (119-287)


Balancing Concerns








Ed



0

50

100

150

200

250

USA 1994

Europe 1998

Sweden 1998

Germany 1998

China 1999

Germany 2000

China 2000

Canada 2001

Excess Lung

Cancer Risk

(Percentage)


Higher Exposure

Work Only -

Higher Exposure


+1-25

+35-220 +50-210























Teachers Cohort[48]

Adjusted HR

(95 CI)

Womenrsquos Health


Adjusted HR (95

CI)


exposure

100 100







126 (099-160) 132(104-167)





























Exposure



40+ cigday

138 (105-183)

174 (115-262)



205 (120-349)


gt20 cigday 183 (129-261)


Initiation 10-14 146 (111-193)

148 (103-213)


(premeno) 39 (15-99)


Hanaoka et al 2004



Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)






Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)

Pooled

Analysis

Never

active

100 100 100 100

lt20 105 (086-128) 123 (103-146) 091 (072-116) 110 (089-135)

gt20 149 (108-204) 142 (116-174) 129 (089-186) 088 (069-113)






initiation

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137)

Al-Delaimy(2004) 129 (097-171)

Reynolds (2004) 117 (105-130)

Lawlor (2004)

Gram (2005) 148 (103-213)

Olson (2005) 112 (092-136)

Cui (2006) 111 (097-128)

Ha (2007) 148 (077-284)

8 of 8 positive

4 of 8 Stat Sig




initiation

Longest duration

before pregnancy

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131)

Al-Delaimy(2004) 129 (097-171) 110 (080-152)

Reynolds (2004) 117 (105-130) 113 (100-125)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137)

Olson (2005) 112 (092-136) 121 (101-125)

Cui (2006) 111 (097-128) 113 (101-125)

Ha (2007) 148 (077-284) 178 (127-249)11

9 of 9 positive

4 of 9 Stat Sig




initiation

Longest duration

before pregnancy

Longest

duration

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189)

Ha (2007) 148 (077-284) 178 (127-249)11

6 of 6 positive

3 of 6 Stat Sig




initiation

Longest duration

Before pregnancy

Longest

duration

Highest pack-

years

Calle (1994) 159 (117-215) 138 (105-183)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133) 125 (106-147)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174) 146 (111-193)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138) 115 (096-137)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189) 117 (102-134)

Ha (2007) 148 (077-284) 178 (127-249)11


5 of 5 positive




First Author Year



Relative Risk

(95 CI)

Reynolds et al (2004) lt20 117 (105-130)

Olson et al (2005) lt19 112 (092-136)

Xue et al (2011) lt18 104 (099-111)

Cui et al (2006) lt16 111 (097-128)


Gram et al (2005) lt15 148 (103-213)

Ha et al (2007) lt15 148 (077-284)



















i
























bull History

bull Lung diseases


bull History

bull Lung disease



TOBACCO SMOKE








INFLAMMATION



LUNG CANCER




ndash COPD

ndash Lung cancer









times








bull History

bull Lung disease












bull History

bull Lung diseases

bull COPD









bull Findings






bull Interpretation







Follow up (y)

Po

stb

ron

cho

dila

tor

FEV

1 L

24

25

26

27

28

29

Screen 2 1 2 3 4 5

Sustained Quitters

Continuous Smokers



COPD










bull Asthma

Asthma








32 subjects


10 quit smoking

Lung cancer













200615517-523















Wen et al--2010




Kolappan Gopi--2002

Thank you




Cancer


Lung

Mouth and pharynx

Larynx

Esophagus

Stomach

Pancreas

Liver

Cervix

Bladder

Kidney

Colorectum

Breast




Body mass index






45-74 years







history from women




51 of the cohort




Heavy smokers (12)


Light smokers (88)





Men (n=27292) Women (n=34028)


Percent 422 214 364 913 25 62


Lung cancer


Never 100

1-12 432 (355-523)

13-22 661 (546-802)

23+ 949 (758-1188)

P for trend lt00001

Smoking status

Lung cancer

RR (95 CI)

Never 100

Former 224 (181-278)

Current 585 (499-687)







Body Mass

Index (kgm2)

Never

smokers

Former

smokers

Current

smokers

Adj HR

(95 CI)

Adj HR

(95 CI)

Adj HR

(95 CI)

lt20 100 100 100

20-lt24 102 (071-146) 092 (057-148) 081 (067-099)

24-lt28 072 (046-110) 101 (059-174) 062 (046-082)

28+ 081 (046-144) 097 (044-212) 050 (028-088)

P for trend 008 089 00001



Smoking

status



Never 100 100 100 100

Former 246

(140-432)

197

(148-262)

296

(184-476)

199

(088-452)

Current 721

(484-1075)

520

(422-641)

550

(364-832)

321

(158-651)





1-12 618

(398-958)

365

(282-473)

365

(212-628)

290

(115-727)

13-22 792

(501-1253)

639

(498-820)

541

(323-905)

221

(071-686)

23+ 1112

(660-1870)

853

(635-1150)

901

(504-1610)

637

(210-1930)

P trend lt00001 lt00001 lt00001 00001




of lung cancer





damage





weights



developed world



Obesity

Western diet

Physical inactivity

Smoking







GST enzymes







GSTP1 polymorphism







Smokers














us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang


















01

1

10H

iray

am

a 199

2W

arte

nb

erg

et

al

200

0R

eyn

old

s e

t a

l 20

04

Ha

nao

ka e

t al

200

4S

an

dle

r e

t al 1

985

Millik

an

et

al 1

998

De

lfin

o e

t al

2000

Scru

bso

le e

t al

2004

Gam

mon

et a

l 200

4S

mit

h e

t al

1994

Mo

rab

ia e

t al 1

996

Zh

ao

et

al

1999

Jo

hn

so

n e

t al

200

0K

ro

pp

et

al

200

2L

isso

wsk

a e

t al 2

00

6M

issed

Ex

po

su

re -

Co

ho

rt

Stu

die

s

Mis

sed

Ex

po

su

re -

Cas

e-C

on

tro

l

Be

tte

r E

xp

osu

re

Asses

sm

en

t



|______________________________________|



|_____________________|

Cohort

|___________________________|

Case-control






















cancerrdquo



2005 1

Surgeon Generals

Report 20062


(95 CI)

N Relative Risk

(95 CI)

All studies 19 125 (108-144) 21 120 (108-135)

Premenopausal

Women lt 50

14 168 (131-215) 11 164 (125-214)

Premenopausal

with lifetime

exposure

assessment

5 220 (169-287) 6 185 (119-287)


Balancing Concerns








Ed



0

50

100

150

200

250

USA 1994

Europe 1998

Sweden 1998

Germany 1998

China 1999

Germany 2000

China 2000

Canada 2001

Excess Lung

Cancer Risk

(Percentage)


Higher Exposure

Work Only -

Higher Exposure


+1-25

+35-220 +50-210























Teachers Cohort[48]

Adjusted HR

(95 CI)

Womenrsquos Health


Adjusted HR (95

CI)


exposure

100 100







126 (099-160) 132(104-167)





























Exposure



40+ cigday

138 (105-183)

174 (115-262)



205 (120-349)


gt20 cigday 183 (129-261)


Initiation 10-14 146 (111-193)

148 (103-213)


(premeno) 39 (15-99)


Hanaoka et al 2004



Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)






Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)

Pooled

Analysis

Never

active

100 100 100 100

lt20 105 (086-128) 123 (103-146) 091 (072-116) 110 (089-135)

gt20 149 (108-204) 142 (116-174) 129 (089-186) 088 (069-113)






initiation

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137)

Al-Delaimy(2004) 129 (097-171)

Reynolds (2004) 117 (105-130)

Lawlor (2004)

Gram (2005) 148 (103-213)

Olson (2005) 112 (092-136)

Cui (2006) 111 (097-128)

Ha (2007) 148 (077-284)

8 of 8 positive

4 of 8 Stat Sig




initiation

Longest duration

before pregnancy

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131)

Al-Delaimy(2004) 129 (097-171) 110 (080-152)

Reynolds (2004) 117 (105-130) 113 (100-125)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137)

Olson (2005) 112 (092-136) 121 (101-125)

Cui (2006) 111 (097-128) 113 (101-125)

Ha (2007) 148 (077-284) 178 (127-249)11

9 of 9 positive

4 of 9 Stat Sig




initiation

Longest duration

before pregnancy

Longest

duration

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189)

Ha (2007) 148 (077-284) 178 (127-249)11

6 of 6 positive

3 of 6 Stat Sig




initiation

Longest duration

Before pregnancy

Longest

duration

Highest pack-

years

Calle (1994) 159 (117-215) 138 (105-183)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133) 125 (106-147)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174) 146 (111-193)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138) 115 (096-137)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189) 117 (102-134)

Ha (2007) 148 (077-284) 178 (127-249)11


5 of 5 positive




First Author Year



Relative Risk

(95 CI)

Reynolds et al (2004) lt20 117 (105-130)

Olson et al (2005) lt19 112 (092-136)

Xue et al (2011) lt18 104 (099-111)

Cui et al (2006) lt16 111 (097-128)


Gram et al (2005) lt15 148 (103-213)

Ha et al (2007) lt15 148 (077-284)



















i
























bull History

bull Lung diseases


bull History

bull Lung disease



TOBACCO SMOKE








INFLAMMATION



LUNG CANCER




ndash COPD

ndash Lung cancer









times








bull History

bull Lung disease












bull History

bull Lung diseases

bull COPD









bull Findings






bull Interpretation







Follow up (y)

Po

stb

ron

cho

dila

tor

FEV

1 L

24

25

26

27

28

29

Screen 2 1 2 3 4 5

Sustained Quitters

Continuous Smokers



COPD










bull Asthma

Asthma








32 subjects


10 quit smoking

Lung cancer













200615517-523















Wen et al--2010




Kolappan Gopi--2002

Thank you




Cancer


Lung

Mouth and pharynx

Larynx

Esophagus

Stomach

Pancreas

Liver

Cervix

Bladder

Kidney

Colorectum

Breast




Body mass index






45-74 years







history from women




51 of the cohort




Heavy smokers (12)


Light smokers (88)





Men (n=27292) Women (n=34028)


Percent 422 214 364 913 25 62


Lung cancer


Never 100

1-12 432 (355-523)

13-22 661 (546-802)

23+ 949 (758-1188)

P for trend lt00001

Smoking status

Lung cancer

RR (95 CI)

Never 100

Former 224 (181-278)

Current 585 (499-687)







Body Mass

Index (kgm2)

Never

smokers

Former

smokers

Current

smokers

Adj HR

(95 CI)

Adj HR

(95 CI)

Adj HR

(95 CI)

lt20 100 100 100

20-lt24 102 (071-146) 092 (057-148) 081 (067-099)

24-lt28 072 (046-110) 101 (059-174) 062 (046-082)

28+ 081 (046-144) 097 (044-212) 050 (028-088)

P for trend 008 089 00001



Smoking

status



Never 100 100 100 100

Former 246

(140-432)

197

(148-262)

296

(184-476)

199

(088-452)

Current 721

(484-1075)

520

(422-641)

550

(364-832)

321

(158-651)





1-12 618

(398-958)

365

(282-473)

365

(212-628)

290

(115-727)

13-22 792

(501-1253)

639

(498-820)

541

(323-905)

221

(071-686)

23+ 1112

(660-1870)

853

(635-1150)

901

(504-1610)

637

(210-1930)

P trend lt00001 lt00001 lt00001 00001




of lung cancer





damage





weights



developed world



Obesity

Western diet

Physical inactivity

Smoking







GST enzymes







GSTP1 polymorphism







Smokers














us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang


























cancerrdquo



2005 1

Surgeon Generals

Report 20062


(95 CI)

N Relative Risk

(95 CI)

All studies 19 125 (108-144) 21 120 (108-135)

Premenopausal

Women lt 50

14 168 (131-215) 11 164 (125-214)

Premenopausal

with lifetime

exposure

assessment

5 220 (169-287) 6 185 (119-287)


Balancing Concerns








Ed



0

50

100

150

200

250

USA 1994

Europe 1998

Sweden 1998

Germany 1998

China 1999

Germany 2000

China 2000

Canada 2001

Excess Lung

Cancer Risk

(Percentage)


Higher Exposure

Work Only -

Higher Exposure


+1-25

+35-220 +50-210























Teachers Cohort[48]

Adjusted HR

(95 CI)

Womenrsquos Health


Adjusted HR (95

CI)


exposure

100 100







126 (099-160) 132(104-167)





























Exposure



40+ cigday

138 (105-183)

174 (115-262)



205 (120-349)


gt20 cigday 183 (129-261)


Initiation 10-14 146 (111-193)

148 (103-213)


(premeno) 39 (15-99)


Hanaoka et al 2004



Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)






Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)

Pooled

Analysis

Never

active

100 100 100 100

lt20 105 (086-128) 123 (103-146) 091 (072-116) 110 (089-135)

gt20 149 (108-204) 142 (116-174) 129 (089-186) 088 (069-113)






initiation

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137)

Al-Delaimy(2004) 129 (097-171)

Reynolds (2004) 117 (105-130)

Lawlor (2004)

Gram (2005) 148 (103-213)

Olson (2005) 112 (092-136)

Cui (2006) 111 (097-128)

Ha (2007) 148 (077-284)

8 of 8 positive

4 of 8 Stat Sig




initiation

Longest duration

before pregnancy

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131)

Al-Delaimy(2004) 129 (097-171) 110 (080-152)

Reynolds (2004) 117 (105-130) 113 (100-125)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137)

Olson (2005) 112 (092-136) 121 (101-125)

Cui (2006) 111 (097-128) 113 (101-125)

Ha (2007) 148 (077-284) 178 (127-249)11

9 of 9 positive

4 of 9 Stat Sig




initiation

Longest duration

before pregnancy

Longest

duration

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189)

Ha (2007) 148 (077-284) 178 (127-249)11

6 of 6 positive

3 of 6 Stat Sig




initiation

Longest duration

Before pregnancy

Longest

duration

Highest pack-

years

Calle (1994) 159 (117-215) 138 (105-183)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133) 125 (106-147)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174) 146 (111-193)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138) 115 (096-137)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189) 117 (102-134)

Ha (2007) 148 (077-284) 178 (127-249)11


5 of 5 positive




First Author Year



Relative Risk

(95 CI)

Reynolds et al (2004) lt20 117 (105-130)

Olson et al (2005) lt19 112 (092-136)

Xue et al (2011) lt18 104 (099-111)

Cui et al (2006) lt16 111 (097-128)


Gram et al (2005) lt15 148 (103-213)

Ha et al (2007) lt15 148 (077-284)



















i
























bull History

bull Lung diseases


bull History

bull Lung disease



TOBACCO SMOKE








INFLAMMATION



LUNG CANCER




ndash COPD

ndash Lung cancer









times








bull History

bull Lung disease












bull History

bull Lung diseases

bull COPD









bull Findings






bull Interpretation







Follow up (y)

Po

stb

ron

cho

dila

tor

FEV

1 L

24

25

26

27

28

29

Screen 2 1 2 3 4 5

Sustained Quitters

Continuous Smokers



COPD










bull Asthma

Asthma








32 subjects


10 quit smoking

Lung cancer













200615517-523















Wen et al--2010




Kolappan Gopi--2002

Thank you




Cancer


Lung

Mouth and pharynx

Larynx

Esophagus

Stomach

Pancreas

Liver

Cervix

Bladder

Kidney

Colorectum

Breast




Body mass index






45-74 years







history from women




51 of the cohort




Heavy smokers (12)


Light smokers (88)





Men (n=27292) Women (n=34028)


Percent 422 214 364 913 25 62


Lung cancer


Never 100

1-12 432 (355-523)

13-22 661 (546-802)

23+ 949 (758-1188)

P for trend lt00001

Smoking status

Lung cancer

RR (95 CI)

Never 100

Former 224 (181-278)

Current 585 (499-687)







Body Mass

Index (kgm2)

Never

smokers

Former

smokers

Current

smokers

Adj HR

(95 CI)

Adj HR

(95 CI)

Adj HR

(95 CI)

lt20 100 100 100

20-lt24 102 (071-146) 092 (057-148) 081 (067-099)

24-lt28 072 (046-110) 101 (059-174) 062 (046-082)

28+ 081 (046-144) 097 (044-212) 050 (028-088)

P for trend 008 089 00001



Smoking

status



Never 100 100 100 100

Former 246

(140-432)

197

(148-262)

296

(184-476)

199

(088-452)

Current 721

(484-1075)

520

(422-641)

550

(364-832)

321

(158-651)





1-12 618

(398-958)

365

(282-473)

365

(212-628)

290

(115-727)

13-22 792

(501-1253)

639

(498-820)

541

(323-905)

221

(071-686)

23+ 1112

(660-1870)

853

(635-1150)

901

(504-1610)

637

(210-1930)

P trend lt00001 lt00001 lt00001 00001




of lung cancer





damage





weights



developed world



Obesity

Western diet

Physical inactivity

Smoking







GST enzymes







GSTP1 polymorphism







Smokers














us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang









2005 1

Surgeon Generals

Report 20062


(95 CI)

N Relative Risk

(95 CI)

All studies 19 125 (108-144) 21 120 (108-135)

Premenopausal

Women lt 50

14 168 (131-215) 11 164 (125-214)

Premenopausal

with lifetime

exposure

assessment

5 220 (169-287) 6 185 (119-287)


Balancing Concerns








Ed



0

50

100

150

200

250

USA 1994

Europe 1998

Sweden 1998

Germany 1998

China 1999

Germany 2000

China 2000

Canada 2001

Excess Lung

Cancer Risk

(Percentage)


Higher Exposure

Work Only -

Higher Exposure


+1-25

+35-220 +50-210























Teachers Cohort[48]

Adjusted HR

(95 CI)

Womenrsquos Health


Adjusted HR (95

CI)


exposure

100 100







126 (099-160) 132(104-167)





























Exposure



40+ cigday

138 (105-183)

174 (115-262)



205 (120-349)


gt20 cigday 183 (129-261)


Initiation 10-14 146 (111-193)

148 (103-213)


(premeno) 39 (15-99)


Hanaoka et al 2004



Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)






Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)

Pooled

Analysis

Never

active

100 100 100 100

lt20 105 (086-128) 123 (103-146) 091 (072-116) 110 (089-135)

gt20 149 (108-204) 142 (116-174) 129 (089-186) 088 (069-113)






initiation

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137)

Al-Delaimy(2004) 129 (097-171)

Reynolds (2004) 117 (105-130)

Lawlor (2004)

Gram (2005) 148 (103-213)

Olson (2005) 112 (092-136)

Cui (2006) 111 (097-128)

Ha (2007) 148 (077-284)

8 of 8 positive

4 of 8 Stat Sig




initiation

Longest duration

before pregnancy

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131)

Al-Delaimy(2004) 129 (097-171) 110 (080-152)

Reynolds (2004) 117 (105-130) 113 (100-125)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137)

Olson (2005) 112 (092-136) 121 (101-125)

Cui (2006) 111 (097-128) 113 (101-125)

Ha (2007) 148 (077-284) 178 (127-249)11

9 of 9 positive

4 of 9 Stat Sig




initiation

Longest duration

before pregnancy

Longest

duration

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189)

Ha (2007) 148 (077-284) 178 (127-249)11

6 of 6 positive

3 of 6 Stat Sig




initiation

Longest duration

Before pregnancy

Longest

duration

Highest pack-

years

Calle (1994) 159 (117-215) 138 (105-183)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133) 125 (106-147)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174) 146 (111-193)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138) 115 (096-137)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189) 117 (102-134)

Ha (2007) 148 (077-284) 178 (127-249)11


5 of 5 positive




First Author Year



Relative Risk

(95 CI)

Reynolds et al (2004) lt20 117 (105-130)

Olson et al (2005) lt19 112 (092-136)

Xue et al (2011) lt18 104 (099-111)

Cui et al (2006) lt16 111 (097-128)


Gram et al (2005) lt15 148 (103-213)

Ha et al (2007) lt15 148 (077-284)



















i
























bull History

bull Lung diseases


bull History

bull Lung disease



TOBACCO SMOKE








INFLAMMATION



LUNG CANCER




ndash COPD

ndash Lung cancer









times








bull History

bull Lung disease












bull History

bull Lung diseases

bull COPD









bull Findings






bull Interpretation







Follow up (y)

Po

stb

ron

cho

dila

tor

FEV

1 L

24

25

26

27

28

29

Screen 2 1 2 3 4 5

Sustained Quitters

Continuous Smokers



COPD










bull Asthma

Asthma








32 subjects


10 quit smoking

Lung cancer













200615517-523















Wen et al--2010




Kolappan Gopi--2002

Thank you




Cancer


Lung

Mouth and pharynx

Larynx

Esophagus

Stomach

Pancreas

Liver

Cervix

Bladder

Kidney

Colorectum

Breast




Body mass index






45-74 years







history from women




51 of the cohort




Heavy smokers (12)


Light smokers (88)





Men (n=27292) Women (n=34028)


Percent 422 214 364 913 25 62


Lung cancer


Never 100

1-12 432 (355-523)

13-22 661 (546-802)

23+ 949 (758-1188)

P for trend lt00001

Smoking status

Lung cancer

RR (95 CI)

Never 100

Former 224 (181-278)

Current 585 (499-687)







Body Mass

Index (kgm2)

Never

smokers

Former

smokers

Current

smokers

Adj HR

(95 CI)

Adj HR

(95 CI)

Adj HR

(95 CI)

lt20 100 100 100

20-lt24 102 (071-146) 092 (057-148) 081 (067-099)

24-lt28 072 (046-110) 101 (059-174) 062 (046-082)

28+ 081 (046-144) 097 (044-212) 050 (028-088)

P for trend 008 089 00001



Smoking

status



Never 100 100 100 100

Former 246

(140-432)

197

(148-262)

296

(184-476)

199

(088-452)

Current 721

(484-1075)

520

(422-641)

550

(364-832)

321

(158-651)





1-12 618

(398-958)

365

(282-473)

365

(212-628)

290

(115-727)

13-22 792

(501-1253)

639

(498-820)

541

(323-905)

221

(071-686)

23+ 1112

(660-1870)

853

(635-1150)

901

(504-1610)

637

(210-1930)

P trend lt00001 lt00001 lt00001 00001




of lung cancer





damage





weights



developed world



Obesity

Western diet

Physical inactivity

Smoking







GST enzymes







GSTP1 polymorphism







Smokers














us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang








Balancing Concerns








Ed



0

50

100

150

200

250

USA 1994

Europe 1998

Sweden 1998

Germany 1998

China 1999

Germany 2000

China 2000

Canada 2001

Excess Lung

Cancer Risk

(Percentage)


Higher Exposure

Work Only -

Higher Exposure


+1-25

+35-220 +50-210























Teachers Cohort[48]

Adjusted HR

(95 CI)

Womenrsquos Health


Adjusted HR (95

CI)


exposure

100 100







126 (099-160) 132(104-167)





























Exposure



40+ cigday

138 (105-183)

174 (115-262)



205 (120-349)


gt20 cigday 183 (129-261)


Initiation 10-14 146 (111-193)

148 (103-213)


(premeno) 39 (15-99)


Hanaoka et al 2004



Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)






Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)

Pooled

Analysis

Never

active

100 100 100 100

lt20 105 (086-128) 123 (103-146) 091 (072-116) 110 (089-135)

gt20 149 (108-204) 142 (116-174) 129 (089-186) 088 (069-113)






initiation

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137)

Al-Delaimy(2004) 129 (097-171)

Reynolds (2004) 117 (105-130)

Lawlor (2004)

Gram (2005) 148 (103-213)

Olson (2005) 112 (092-136)

Cui (2006) 111 (097-128)

Ha (2007) 148 (077-284)

8 of 8 positive

4 of 8 Stat Sig




initiation

Longest duration

before pregnancy

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131)

Al-Delaimy(2004) 129 (097-171) 110 (080-152)

Reynolds (2004) 117 (105-130) 113 (100-125)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137)

Olson (2005) 112 (092-136) 121 (101-125)

Cui (2006) 111 (097-128) 113 (101-125)

Ha (2007) 148 (077-284) 178 (127-249)11

9 of 9 positive

4 of 9 Stat Sig




initiation

Longest duration

before pregnancy

Longest

duration

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189)

Ha (2007) 148 (077-284) 178 (127-249)11

6 of 6 positive

3 of 6 Stat Sig




initiation

Longest duration

Before pregnancy

Longest

duration

Highest pack-

years

Calle (1994) 159 (117-215) 138 (105-183)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133) 125 (106-147)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174) 146 (111-193)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138) 115 (096-137)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189) 117 (102-134)

Ha (2007) 148 (077-284) 178 (127-249)11


5 of 5 positive




First Author Year



Relative Risk

(95 CI)

Reynolds et al (2004) lt20 117 (105-130)

Olson et al (2005) lt19 112 (092-136)

Xue et al (2011) lt18 104 (099-111)

Cui et al (2006) lt16 111 (097-128)


Gram et al (2005) lt15 148 (103-213)

Ha et al (2007) lt15 148 (077-284)



















i
























bull History

bull Lung diseases


bull History

bull Lung disease



TOBACCO SMOKE








INFLAMMATION



LUNG CANCER




ndash COPD

ndash Lung cancer









times








bull History

bull Lung disease












bull History

bull Lung diseases

bull COPD









bull Findings






bull Interpretation







Follow up (y)

Po

stb

ron

cho

dila

tor

FEV

1 L

24

25

26

27

28

29

Screen 2 1 2 3 4 5

Sustained Quitters

Continuous Smokers



COPD










bull Asthma

Asthma








32 subjects


10 quit smoking

Lung cancer













200615517-523















Wen et al--2010




Kolappan Gopi--2002

Thank you




Cancer


Lung

Mouth and pharynx

Larynx

Esophagus

Stomach

Pancreas

Liver

Cervix

Bladder

Kidney

Colorectum

Breast




Body mass index






45-74 years







history from women




51 of the cohort




Heavy smokers (12)


Light smokers (88)





Men (n=27292) Women (n=34028)


Percent 422 214 364 913 25 62


Lung cancer


Never 100

1-12 432 (355-523)

13-22 661 (546-802)

23+ 949 (758-1188)

P for trend lt00001

Smoking status

Lung cancer

RR (95 CI)

Never 100

Former 224 (181-278)

Current 585 (499-687)







Body Mass

Index (kgm2)

Never

smokers

Former

smokers

Current

smokers

Adj HR

(95 CI)

Adj HR

(95 CI)

Adj HR

(95 CI)

lt20 100 100 100

20-lt24 102 (071-146) 092 (057-148) 081 (067-099)

24-lt28 072 (046-110) 101 (059-174) 062 (046-082)

28+ 081 (046-144) 097 (044-212) 050 (028-088)

P for trend 008 089 00001



Smoking

status



Never 100 100 100 100

Former 246

(140-432)

197

(148-262)

296

(184-476)

199

(088-452)

Current 721

(484-1075)

520

(422-641)

550

(364-832)

321

(158-651)





1-12 618

(398-958)

365

(282-473)

365

(212-628)

290

(115-727)

13-22 792

(501-1253)

639

(498-820)

541

(323-905)

221

(071-686)

23+ 1112

(660-1870)

853

(635-1150)

901

(504-1610)

637

(210-1930)

P trend lt00001 lt00001 lt00001 00001




of lung cancer





damage





weights



developed world



Obesity

Western diet

Physical inactivity

Smoking







GST enzymes







GSTP1 polymorphism







Smokers














us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang








Ed



0

50

100

150

200

250

USA 1994

Europe 1998

Sweden 1998

Germany 1998

China 1999

Germany 2000

China 2000

Canada 2001

Excess Lung

Cancer Risk

(Percentage)


Higher Exposure

Work Only -

Higher Exposure


+1-25

+35-220 +50-210























Teachers Cohort[48]

Adjusted HR

(95 CI)

Womenrsquos Health


Adjusted HR (95

CI)


exposure

100 100







126 (099-160) 132(104-167)





























Exposure



40+ cigday

138 (105-183)

174 (115-262)



205 (120-349)


gt20 cigday 183 (129-261)


Initiation 10-14 146 (111-193)

148 (103-213)


(premeno) 39 (15-99)


Hanaoka et al 2004



Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)






Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)

Pooled

Analysis

Never

active

100 100 100 100

lt20 105 (086-128) 123 (103-146) 091 (072-116) 110 (089-135)

gt20 149 (108-204) 142 (116-174) 129 (089-186) 088 (069-113)






initiation

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137)

Al-Delaimy(2004) 129 (097-171)

Reynolds (2004) 117 (105-130)

Lawlor (2004)

Gram (2005) 148 (103-213)

Olson (2005) 112 (092-136)

Cui (2006) 111 (097-128)

Ha (2007) 148 (077-284)

8 of 8 positive

4 of 8 Stat Sig




initiation

Longest duration

before pregnancy

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131)

Al-Delaimy(2004) 129 (097-171) 110 (080-152)

Reynolds (2004) 117 (105-130) 113 (100-125)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137)

Olson (2005) 112 (092-136) 121 (101-125)

Cui (2006) 111 (097-128) 113 (101-125)

Ha (2007) 148 (077-284) 178 (127-249)11

9 of 9 positive

4 of 9 Stat Sig




initiation

Longest duration

before pregnancy

Longest

duration

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189)

Ha (2007) 148 (077-284) 178 (127-249)11

6 of 6 positive

3 of 6 Stat Sig




initiation

Longest duration

Before pregnancy

Longest

duration

Highest pack-

years

Calle (1994) 159 (117-215) 138 (105-183)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133) 125 (106-147)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174) 146 (111-193)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138) 115 (096-137)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189) 117 (102-134)

Ha (2007) 148 (077-284) 178 (127-249)11


5 of 5 positive




First Author Year



Relative Risk

(95 CI)

Reynolds et al (2004) lt20 117 (105-130)

Olson et al (2005) lt19 112 (092-136)

Xue et al (2011) lt18 104 (099-111)

Cui et al (2006) lt16 111 (097-128)


Gram et al (2005) lt15 148 (103-213)

Ha et al (2007) lt15 148 (077-284)



















i
























bull History

bull Lung diseases


bull History

bull Lung disease



TOBACCO SMOKE








INFLAMMATION



LUNG CANCER




ndash COPD

ndash Lung cancer









times








bull History

bull Lung disease












bull History

bull Lung diseases

bull COPD









bull Findings






bull Interpretation







Follow up (y)

Po

stb

ron

cho

dila

tor

FEV

1 L

24

25

26

27

28

29

Screen 2 1 2 3 4 5

Sustained Quitters

Continuous Smokers



COPD










bull Asthma

Asthma








32 subjects


10 quit smoking

Lung cancer













200615517-523















Wen et al--2010




Kolappan Gopi--2002

Thank you




Cancer


Lung

Mouth and pharynx

Larynx

Esophagus

Stomach

Pancreas

Liver

Cervix

Bladder

Kidney

Colorectum

Breast




Body mass index






45-74 years







history from women




51 of the cohort




Heavy smokers (12)


Light smokers (88)





Men (n=27292) Women (n=34028)


Percent 422 214 364 913 25 62


Lung cancer


Never 100

1-12 432 (355-523)

13-22 661 (546-802)

23+ 949 (758-1188)

P for trend lt00001

Smoking status

Lung cancer

RR (95 CI)

Never 100

Former 224 (181-278)

Current 585 (499-687)







Body Mass

Index (kgm2)

Never

smokers

Former

smokers

Current

smokers

Adj HR

(95 CI)

Adj HR

(95 CI)

Adj HR

(95 CI)

lt20 100 100 100

20-lt24 102 (071-146) 092 (057-148) 081 (067-099)

24-lt28 072 (046-110) 101 (059-174) 062 (046-082)

28+ 081 (046-144) 097 (044-212) 050 (028-088)

P for trend 008 089 00001



Smoking

status



Never 100 100 100 100

Former 246

(140-432)

197

(148-262)

296

(184-476)

199

(088-452)

Current 721

(484-1075)

520

(422-641)

550

(364-832)

321

(158-651)





1-12 618

(398-958)

365

(282-473)

365

(212-628)

290

(115-727)

13-22 792

(501-1253)

639

(498-820)

541

(323-905)

221

(071-686)

23+ 1112

(660-1870)

853

(635-1150)

901

(504-1610)

637

(210-1930)

P trend lt00001 lt00001 lt00001 00001




of lung cancer





damage





weights



developed world



Obesity

Western diet

Physical inactivity

Smoking







GST enzymes







GSTP1 polymorphism







Smokers














us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang









0

50

100

150

200

250

USA 1994

Europe 1998

Sweden 1998

Germany 1998

China 1999

Germany 2000

China 2000

Canada 2001

Excess Lung

Cancer Risk

(Percentage)


Higher Exposure

Work Only -

Higher Exposure


+1-25

+35-220 +50-210























Teachers Cohort[48]

Adjusted HR

(95 CI)

Womenrsquos Health


Adjusted HR (95

CI)


exposure

100 100







126 (099-160) 132(104-167)





























Exposure



40+ cigday

138 (105-183)

174 (115-262)



205 (120-349)


gt20 cigday 183 (129-261)


Initiation 10-14 146 (111-193)

148 (103-213)


(premeno) 39 (15-99)


Hanaoka et al 2004



Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)






Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)

Pooled

Analysis

Never

active

100 100 100 100

lt20 105 (086-128) 123 (103-146) 091 (072-116) 110 (089-135)

gt20 149 (108-204) 142 (116-174) 129 (089-186) 088 (069-113)






initiation

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137)

Al-Delaimy(2004) 129 (097-171)

Reynolds (2004) 117 (105-130)

Lawlor (2004)

Gram (2005) 148 (103-213)

Olson (2005) 112 (092-136)

Cui (2006) 111 (097-128)

Ha (2007) 148 (077-284)

8 of 8 positive

4 of 8 Stat Sig




initiation

Longest duration

before pregnancy

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131)

Al-Delaimy(2004) 129 (097-171) 110 (080-152)

Reynolds (2004) 117 (105-130) 113 (100-125)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137)

Olson (2005) 112 (092-136) 121 (101-125)

Cui (2006) 111 (097-128) 113 (101-125)

Ha (2007) 148 (077-284) 178 (127-249)11

9 of 9 positive

4 of 9 Stat Sig




initiation

Longest duration

before pregnancy

Longest

duration

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189)

Ha (2007) 148 (077-284) 178 (127-249)11

6 of 6 positive

3 of 6 Stat Sig




initiation

Longest duration

Before pregnancy

Longest

duration

Highest pack-

years

Calle (1994) 159 (117-215) 138 (105-183)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133) 125 (106-147)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174) 146 (111-193)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138) 115 (096-137)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189) 117 (102-134)

Ha (2007) 148 (077-284) 178 (127-249)11


5 of 5 positive




First Author Year



Relative Risk

(95 CI)

Reynolds et al (2004) lt20 117 (105-130)

Olson et al (2005) lt19 112 (092-136)

Xue et al (2011) lt18 104 (099-111)

Cui et al (2006) lt16 111 (097-128)


Gram et al (2005) lt15 148 (103-213)

Ha et al (2007) lt15 148 (077-284)



















i
























bull History

bull Lung diseases


bull History

bull Lung disease



TOBACCO SMOKE








INFLAMMATION



LUNG CANCER




ndash COPD

ndash Lung cancer









times








bull History

bull Lung disease












bull History

bull Lung diseases

bull COPD









bull Findings






bull Interpretation







Follow up (y)

Po

stb

ron

cho

dila

tor

FEV

1 L

24

25

26

27

28

29

Screen 2 1 2 3 4 5

Sustained Quitters

Continuous Smokers



COPD










bull Asthma

Asthma








32 subjects


10 quit smoking

Lung cancer













200615517-523















Wen et al--2010




Kolappan Gopi--2002

Thank you




Cancer


Lung

Mouth and pharynx

Larynx

Esophagus

Stomach

Pancreas

Liver

Cervix

Bladder

Kidney

Colorectum

Breast




Body mass index






45-74 years







history from women




51 of the cohort




Heavy smokers (12)


Light smokers (88)





Men (n=27292) Women (n=34028)


Percent 422 214 364 913 25 62


Lung cancer


Never 100

1-12 432 (355-523)

13-22 661 (546-802)

23+ 949 (758-1188)

P for trend lt00001

Smoking status

Lung cancer

RR (95 CI)

Never 100

Former 224 (181-278)

Current 585 (499-687)







Body Mass

Index (kgm2)

Never

smokers

Former

smokers

Current

smokers

Adj HR

(95 CI)

Adj HR

(95 CI)

Adj HR

(95 CI)

lt20 100 100 100

20-lt24 102 (071-146) 092 (057-148) 081 (067-099)

24-lt28 072 (046-110) 101 (059-174) 062 (046-082)

28+ 081 (046-144) 097 (044-212) 050 (028-088)

P for trend 008 089 00001



Smoking

status



Never 100 100 100 100

Former 246

(140-432)

197

(148-262)

296

(184-476)

199

(088-452)

Current 721

(484-1075)

520

(422-641)

550

(364-832)

321

(158-651)





1-12 618

(398-958)

365

(282-473)

365

(212-628)

290

(115-727)

13-22 792

(501-1253)

639

(498-820)

541

(323-905)

221

(071-686)

23+ 1112

(660-1870)

853

(635-1150)

901

(504-1610)

637

(210-1930)

P trend lt00001 lt00001 lt00001 00001




of lung cancer





damage





weights



developed world



Obesity

Western diet

Physical inactivity

Smoking







GST enzymes







GSTP1 polymorphism







Smokers














us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang





























Teachers Cohort[48]

Adjusted HR

(95 CI)

Womenrsquos Health


Adjusted HR (95

CI)


exposure

100 100







126 (099-160) 132(104-167)





























Exposure



40+ cigday

138 (105-183)

174 (115-262)



205 (120-349)


gt20 cigday 183 (129-261)


Initiation 10-14 146 (111-193)

148 (103-213)


(premeno) 39 (15-99)


Hanaoka et al 2004



Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)






Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)

Pooled

Analysis

Never

active

100 100 100 100

lt20 105 (086-128) 123 (103-146) 091 (072-116) 110 (089-135)

gt20 149 (108-204) 142 (116-174) 129 (089-186) 088 (069-113)






initiation

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137)

Al-Delaimy(2004) 129 (097-171)

Reynolds (2004) 117 (105-130)

Lawlor (2004)

Gram (2005) 148 (103-213)

Olson (2005) 112 (092-136)

Cui (2006) 111 (097-128)

Ha (2007) 148 (077-284)

8 of 8 positive

4 of 8 Stat Sig




initiation

Longest duration

before pregnancy

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131)

Al-Delaimy(2004) 129 (097-171) 110 (080-152)

Reynolds (2004) 117 (105-130) 113 (100-125)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137)

Olson (2005) 112 (092-136) 121 (101-125)

Cui (2006) 111 (097-128) 113 (101-125)

Ha (2007) 148 (077-284) 178 (127-249)11

9 of 9 positive

4 of 9 Stat Sig




initiation

Longest duration

before pregnancy

Longest

duration

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189)

Ha (2007) 148 (077-284) 178 (127-249)11

6 of 6 positive

3 of 6 Stat Sig




initiation

Longest duration

Before pregnancy

Longest

duration

Highest pack-

years

Calle (1994) 159 (117-215) 138 (105-183)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133) 125 (106-147)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174) 146 (111-193)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138) 115 (096-137)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189) 117 (102-134)

Ha (2007) 148 (077-284) 178 (127-249)11


5 of 5 positive




First Author Year



Relative Risk

(95 CI)

Reynolds et al (2004) lt20 117 (105-130)

Olson et al (2005) lt19 112 (092-136)

Xue et al (2011) lt18 104 (099-111)

Cui et al (2006) lt16 111 (097-128)


Gram et al (2005) lt15 148 (103-213)

Ha et al (2007) lt15 148 (077-284)



















i
























bull History

bull Lung diseases


bull History

bull Lung disease



TOBACCO SMOKE








INFLAMMATION



LUNG CANCER




ndash COPD

ndash Lung cancer









times








bull History

bull Lung disease












bull History

bull Lung diseases

bull COPD









bull Findings






bull Interpretation







Follow up (y)

Po

stb

ron

cho

dila

tor

FEV

1 L

24

25

26

27

28

29

Screen 2 1 2 3 4 5

Sustained Quitters

Continuous Smokers



COPD










bull Asthma

Asthma








32 subjects


10 quit smoking

Lung cancer













200615517-523















Wen et al--2010




Kolappan Gopi--2002

Thank you




Cancer


Lung

Mouth and pharynx

Larynx

Esophagus

Stomach

Pancreas

Liver

Cervix

Bladder

Kidney

Colorectum

Breast




Body mass index






45-74 years







history from women




51 of the cohort




Heavy smokers (12)


Light smokers (88)





Men (n=27292) Women (n=34028)


Percent 422 214 364 913 25 62


Lung cancer


Never 100

1-12 432 (355-523)

13-22 661 (546-802)

23+ 949 (758-1188)

P for trend lt00001

Smoking status

Lung cancer

RR (95 CI)

Never 100

Former 224 (181-278)

Current 585 (499-687)







Body Mass

Index (kgm2)

Never

smokers

Former

smokers

Current

smokers

Adj HR

(95 CI)

Adj HR

(95 CI)

Adj HR

(95 CI)

lt20 100 100 100

20-lt24 102 (071-146) 092 (057-148) 081 (067-099)

24-lt28 072 (046-110) 101 (059-174) 062 (046-082)

28+ 081 (046-144) 097 (044-212) 050 (028-088)

P for trend 008 089 00001



Smoking

status



Never 100 100 100 100

Former 246

(140-432)

197

(148-262)

296

(184-476)

199

(088-452)

Current 721

(484-1075)

520

(422-641)

550

(364-832)

321

(158-651)





1-12 618

(398-958)

365

(282-473)

365

(212-628)

290

(115-727)

13-22 792

(501-1253)

639

(498-820)

541

(323-905)

221

(071-686)

23+ 1112

(660-1870)

853

(635-1150)

901

(504-1610)

637

(210-1930)

P trend lt00001 lt00001 lt00001 00001




of lung cancer





damage





weights



developed world



Obesity

Western diet

Physical inactivity

Smoking







GST enzymes







GSTP1 polymorphism







Smokers














us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang



































Exposure



40+ cigday

138 (105-183)

174 (115-262)



205 (120-349)


gt20 cigday 183 (129-261)


Initiation 10-14 146 (111-193)

148 (103-213)


(premeno) 39 (15-99)


Hanaoka et al 2004



Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)






Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)

Pooled

Analysis

Never

active

100 100 100 100

lt20 105 (086-128) 123 (103-146) 091 (072-116) 110 (089-135)

gt20 149 (108-204) 142 (116-174) 129 (089-186) 088 (069-113)






initiation

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137)

Al-Delaimy(2004) 129 (097-171)

Reynolds (2004) 117 (105-130)

Lawlor (2004)

Gram (2005) 148 (103-213)

Olson (2005) 112 (092-136)

Cui (2006) 111 (097-128)

Ha (2007) 148 (077-284)

8 of 8 positive

4 of 8 Stat Sig




initiation

Longest duration

before pregnancy

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131)

Al-Delaimy(2004) 129 (097-171) 110 (080-152)

Reynolds (2004) 117 (105-130) 113 (100-125)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137)

Olson (2005) 112 (092-136) 121 (101-125)

Cui (2006) 111 (097-128) 113 (101-125)

Ha (2007) 148 (077-284) 178 (127-249)11

9 of 9 positive

4 of 9 Stat Sig




initiation

Longest duration

before pregnancy

Longest

duration

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189)

Ha (2007) 148 (077-284) 178 (127-249)11

6 of 6 positive

3 of 6 Stat Sig




initiation

Longest duration

Before pregnancy

Longest

duration

Highest pack-

years

Calle (1994) 159 (117-215) 138 (105-183)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133) 125 (106-147)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174) 146 (111-193)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138) 115 (096-137)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189) 117 (102-134)

Ha (2007) 148 (077-284) 178 (127-249)11


5 of 5 positive




First Author Year



Relative Risk

(95 CI)

Reynolds et al (2004) lt20 117 (105-130)

Olson et al (2005) lt19 112 (092-136)

Xue et al (2011) lt18 104 (099-111)

Cui et al (2006) lt16 111 (097-128)


Gram et al (2005) lt15 148 (103-213)

Ha et al (2007) lt15 148 (077-284)



















i
























bull History

bull Lung diseases


bull History

bull Lung disease



TOBACCO SMOKE








INFLAMMATION



LUNG CANCER




ndash COPD

ndash Lung cancer









times








bull History

bull Lung disease












bull History

bull Lung diseases

bull COPD









bull Findings






bull Interpretation







Follow up (y)

Po

stb

ron

cho

dila

tor

FEV

1 L

24

25

26

27

28

29

Screen 2 1 2 3 4 5

Sustained Quitters

Continuous Smokers



COPD










bull Asthma

Asthma








32 subjects


10 quit smoking

Lung cancer













200615517-523















Wen et al--2010




Kolappan Gopi--2002

Thank you




Cancer


Lung

Mouth and pharynx

Larynx

Esophagus

Stomach

Pancreas

Liver

Cervix

Bladder

Kidney

Colorectum

Breast




Body mass index






45-74 years







history from women




51 of the cohort




Heavy smokers (12)


Light smokers (88)





Men (n=27292) Women (n=34028)


Percent 422 214 364 913 25 62


Lung cancer


Never 100

1-12 432 (355-523)

13-22 661 (546-802)

23+ 949 (758-1188)

P for trend lt00001

Smoking status

Lung cancer

RR (95 CI)

Never 100

Former 224 (181-278)

Current 585 (499-687)







Body Mass

Index (kgm2)

Never

smokers

Former

smokers

Current

smokers

Adj HR

(95 CI)

Adj HR

(95 CI)

Adj HR

(95 CI)

lt20 100 100 100

20-lt24 102 (071-146) 092 (057-148) 081 (067-099)

24-lt28 072 (046-110) 101 (059-174) 062 (046-082)

28+ 081 (046-144) 097 (044-212) 050 (028-088)

P for trend 008 089 00001



Smoking

status



Never 100 100 100 100

Former 246

(140-432)

197

(148-262)

296

(184-476)

199

(088-452)

Current 721

(484-1075)

520

(422-641)

550

(364-832)

321

(158-651)





1-12 618

(398-958)

365

(282-473)

365

(212-628)

290

(115-727)

13-22 792

(501-1253)

639

(498-820)

541

(323-905)

221

(071-686)

23+ 1112

(660-1870)

853

(635-1150)

901

(504-1610)

637

(210-1930)

P trend lt00001 lt00001 lt00001 00001




of lung cancer





damage





weights



developed world



Obesity

Western diet

Physical inactivity

Smoking







GST enzymes







GSTP1 polymorphism







Smokers














us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang









Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)






Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)

Pooled

Analysis

Never

active

100 100 100 100

lt20 105 (086-128) 123 (103-146) 091 (072-116) 110 (089-135)

gt20 149 (108-204) 142 (116-174) 129 (089-186) 088 (069-113)






initiation

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137)

Al-Delaimy(2004) 129 (097-171)

Reynolds (2004) 117 (105-130)

Lawlor (2004)

Gram (2005) 148 (103-213)

Olson (2005) 112 (092-136)

Cui (2006) 111 (097-128)

Ha (2007) 148 (077-284)

8 of 8 positive

4 of 8 Stat Sig




initiation

Longest duration

before pregnancy

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131)

Al-Delaimy(2004) 129 (097-171) 110 (080-152)

Reynolds (2004) 117 (105-130) 113 (100-125)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137)

Olson (2005) 112 (092-136) 121 (101-125)

Cui (2006) 111 (097-128) 113 (101-125)

Ha (2007) 148 (077-284) 178 (127-249)11

9 of 9 positive

4 of 9 Stat Sig




initiation

Longest duration

before pregnancy

Longest

duration

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189)

Ha (2007) 148 (077-284) 178 (127-249)11

6 of 6 positive

3 of 6 Stat Sig




initiation

Longest duration

Before pregnancy

Longest

duration

Highest pack-

years

Calle (1994) 159 (117-215) 138 (105-183)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133) 125 (106-147)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174) 146 (111-193)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138) 115 (096-137)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189) 117 (102-134)

Ha (2007) 148 (077-284) 178 (127-249)11


5 of 5 positive




First Author Year



Relative Risk

(95 CI)

Reynolds et al (2004) lt20 117 (105-130)

Olson et al (2005) lt19 112 (092-136)

Xue et al (2011) lt18 104 (099-111)

Cui et al (2006) lt16 111 (097-128)


Gram et al (2005) lt15 148 (103-213)

Ha et al (2007) lt15 148 (077-284)



















i
























bull History

bull Lung diseases


bull History

bull Lung disease



TOBACCO SMOKE








INFLAMMATION



LUNG CANCER




ndash COPD

ndash Lung cancer









times








bull History

bull Lung disease












bull History

bull Lung diseases

bull COPD









bull Findings






bull Interpretation







Follow up (y)

Po

stb

ron

cho

dila

tor

FEV

1 L

24

25

26

27

28

29

Screen 2 1 2 3 4 5

Sustained Quitters

Continuous Smokers



COPD










bull Asthma

Asthma








32 subjects


10 quit smoking

Lung cancer













200615517-523















Wen et al--2010




Kolappan Gopi--2002

Thank you




Cancer


Lung

Mouth and pharynx

Larynx

Esophagus

Stomach

Pancreas

Liver

Cervix

Bladder

Kidney

Colorectum

Breast




Body mass index






45-74 years







history from women




51 of the cohort




Heavy smokers (12)


Light smokers (88)





Men (n=27292) Women (n=34028)


Percent 422 214 364 913 25 62


Lung cancer


Never 100

1-12 432 (355-523)

13-22 661 (546-802)

23+ 949 (758-1188)

P for trend lt00001

Smoking status

Lung cancer

RR (95 CI)

Never 100

Former 224 (181-278)

Current 585 (499-687)







Body Mass

Index (kgm2)

Never

smokers

Former

smokers

Current

smokers

Adj HR

(95 CI)

Adj HR

(95 CI)

Adj HR

(95 CI)

lt20 100 100 100

20-lt24 102 (071-146) 092 (057-148) 081 (067-099)

24-lt28 072 (046-110) 101 (059-174) 062 (046-082)

28+ 081 (046-144) 097 (044-212) 050 (028-088)

P for trend 008 089 00001



Smoking

status



Never 100 100 100 100

Former 246

(140-432)

197

(148-262)

296

(184-476)

199

(088-452)

Current 721

(484-1075)

520

(422-641)

550

(364-832)

321

(158-651)





1-12 618

(398-958)

365

(282-473)

365

(212-628)

290

(115-727)

13-22 792

(501-1253)

639

(498-820)

541

(323-905)

221

(071-686)

23+ 1112

(660-1870)

853

(635-1150)

901

(504-1610)

637

(210-1930)

P trend lt00001 lt00001 lt00001 00001




of lung cancer





damage





weights



developed world



Obesity

Western diet

Physical inactivity

Smoking







GST enzymes







GSTP1 polymorphism







Smokers














us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang









Type of

Analysis

Pack-


Meta-

Analysis

Never

active

100 100 100 100

lt20 121 (100-145) 128 (108-150) 100 (080-124) 112 (093-136)

gt20 147 (108-201) 141 (115-172) 134 (094-189) 098 (077-126)

Pooled

Analysis

Never

active

100 100 100 100

lt20 105 (086-128) 123 (103-146) 091 (072-116) 110 (089-135)

gt20 149 (108-204) 142 (116-174) 129 (089-186) 088 (069-113)






initiation

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137)

Al-Delaimy(2004) 129 (097-171)

Reynolds (2004) 117 (105-130)

Lawlor (2004)

Gram (2005) 148 (103-213)

Olson (2005) 112 (092-136)

Cui (2006) 111 (097-128)

Ha (2007) 148 (077-284)

8 of 8 positive

4 of 8 Stat Sig




initiation

Longest duration

before pregnancy

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131)

Al-Delaimy(2004) 129 (097-171) 110 (080-152)

Reynolds (2004) 117 (105-130) 113 (100-125)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137)

Olson (2005) 112 (092-136) 121 (101-125)

Cui (2006) 111 (097-128) 113 (101-125)

Ha (2007) 148 (077-284) 178 (127-249)11

9 of 9 positive

4 of 9 Stat Sig




initiation

Longest duration

before pregnancy

Longest

duration

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189)

Ha (2007) 148 (077-284) 178 (127-249)11

6 of 6 positive

3 of 6 Stat Sig




initiation

Longest duration

Before pregnancy

Longest

duration

Highest pack-

years

Calle (1994) 159 (117-215) 138 (105-183)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133) 125 (106-147)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174) 146 (111-193)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138) 115 (096-137)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189) 117 (102-134)

Ha (2007) 148 (077-284) 178 (127-249)11


5 of 5 positive




First Author Year



Relative Risk

(95 CI)

Reynolds et al (2004) lt20 117 (105-130)

Olson et al (2005) lt19 112 (092-136)

Xue et al (2011) lt18 104 (099-111)

Cui et al (2006) lt16 111 (097-128)


Gram et al (2005) lt15 148 (103-213)

Ha et al (2007) lt15 148 (077-284)



















i
























bull History

bull Lung diseases


bull History

bull Lung disease



TOBACCO SMOKE








INFLAMMATION



LUNG CANCER




ndash COPD

ndash Lung cancer









times








bull History

bull Lung disease












bull History

bull Lung diseases

bull COPD









bull Findings






bull Interpretation







Follow up (y)

Po

stb

ron

cho

dila

tor

FEV

1 L

24

25

26

27

28

29

Screen 2 1 2 3 4 5

Sustained Quitters

Continuous Smokers



COPD










bull Asthma

Asthma








32 subjects


10 quit smoking

Lung cancer













200615517-523















Wen et al--2010




Kolappan Gopi--2002

Thank you




Cancer


Lung

Mouth and pharynx

Larynx

Esophagus

Stomach

Pancreas

Liver

Cervix

Bladder

Kidney

Colorectum

Breast




Body mass index






45-74 years







history from women




51 of the cohort




Heavy smokers (12)


Light smokers (88)





Men (n=27292) Women (n=34028)


Percent 422 214 364 913 25 62


Lung cancer


Never 100

1-12 432 (355-523)

13-22 661 (546-802)

23+ 949 (758-1188)

P for trend lt00001

Smoking status

Lung cancer

RR (95 CI)

Never 100

Former 224 (181-278)

Current 585 (499-687)







Body Mass

Index (kgm2)

Never

smokers

Former

smokers

Current

smokers

Adj HR

(95 CI)

Adj HR

(95 CI)

Adj HR

(95 CI)

lt20 100 100 100

20-lt24 102 (071-146) 092 (057-148) 081 (067-099)

24-lt28 072 (046-110) 101 (059-174) 062 (046-082)

28+ 081 (046-144) 097 (044-212) 050 (028-088)

P for trend 008 089 00001



Smoking

status



Never 100 100 100 100

Former 246

(140-432)

197

(148-262)

296

(184-476)

199

(088-452)

Current 721

(484-1075)

520

(422-641)

550

(364-832)

321

(158-651)





1-12 618

(398-958)

365

(282-473)

365

(212-628)

290

(115-727)

13-22 792

(501-1253)

639

(498-820)

541

(323-905)

221

(071-686)

23+ 1112

(660-1870)

853

(635-1150)

901

(504-1610)

637

(210-1930)

P trend lt00001 lt00001 lt00001 00001




of lung cancer





damage





weights



developed world



Obesity

Western diet

Physical inactivity

Smoking







GST enzymes







GSTP1 polymorphism







Smokers














us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang









initiation

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137)

Al-Delaimy(2004) 129 (097-171)

Reynolds (2004) 117 (105-130)

Lawlor (2004)

Gram (2005) 148 (103-213)

Olson (2005) 112 (092-136)

Cui (2006) 111 (097-128)

Ha (2007) 148 (077-284)

8 of 8 positive

4 of 8 Stat Sig




initiation

Longest duration

before pregnancy

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131)

Al-Delaimy(2004) 129 (097-171) 110 (080-152)

Reynolds (2004) 117 (105-130) 113 (100-125)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137)

Olson (2005) 112 (092-136) 121 (101-125)

Cui (2006) 111 (097-128) 113 (101-125)

Ha (2007) 148 (077-284) 178 (127-249)11

9 of 9 positive

4 of 9 Stat Sig




initiation

Longest duration

before pregnancy

Longest

duration

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189)

Ha (2007) 148 (077-284) 178 (127-249)11

6 of 6 positive

3 of 6 Stat Sig




initiation

Longest duration

Before pregnancy

Longest

duration

Highest pack-

years

Calle (1994) 159 (117-215) 138 (105-183)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133) 125 (106-147)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174) 146 (111-193)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138) 115 (096-137)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189) 117 (102-134)

Ha (2007) 148 (077-284) 178 (127-249)11


5 of 5 positive




First Author Year



Relative Risk

(95 CI)

Reynolds et al (2004) lt20 117 (105-130)

Olson et al (2005) lt19 112 (092-136)

Xue et al (2011) lt18 104 (099-111)

Cui et al (2006) lt16 111 (097-128)


Gram et al (2005) lt15 148 (103-213)

Ha et al (2007) lt15 148 (077-284)



















i
























bull History

bull Lung diseases


bull History

bull Lung disease



TOBACCO SMOKE








INFLAMMATION



LUNG CANCER




ndash COPD

ndash Lung cancer









times








bull History

bull Lung disease












bull History

bull Lung diseases

bull COPD









bull Findings






bull Interpretation







Follow up (y)

Po

stb

ron

cho

dila

tor

FEV

1 L

24

25

26

27

28

29

Screen 2 1 2 3 4 5

Sustained Quitters

Continuous Smokers



COPD










bull Asthma

Asthma








32 subjects


10 quit smoking

Lung cancer













200615517-523















Wen et al--2010




Kolappan Gopi--2002

Thank you




Cancer


Lung

Mouth and pharynx

Larynx

Esophagus

Stomach

Pancreas

Liver

Cervix

Bladder

Kidney

Colorectum

Breast




Body mass index






45-74 years







history from women




51 of the cohort




Heavy smokers (12)


Light smokers (88)





Men (n=27292) Women (n=34028)


Percent 422 214 364 913 25 62


Lung cancer


Never 100

1-12 432 (355-523)

13-22 661 (546-802)

23+ 949 (758-1188)

P for trend lt00001

Smoking status

Lung cancer

RR (95 CI)

Never 100

Former 224 (181-278)

Current 585 (499-687)







Body Mass

Index (kgm2)

Never

smokers

Former

smokers

Current

smokers

Adj HR

(95 CI)

Adj HR

(95 CI)

Adj HR

(95 CI)

lt20 100 100 100

20-lt24 102 (071-146) 092 (057-148) 081 (067-099)

24-lt28 072 (046-110) 101 (059-174) 062 (046-082)

28+ 081 (046-144) 097 (044-212) 050 (028-088)

P for trend 008 089 00001



Smoking

status



Never 100 100 100 100

Former 246

(140-432)

197

(148-262)

296

(184-476)

199

(088-452)

Current 721

(484-1075)

520

(422-641)

550

(364-832)

321

(158-651)





1-12 618

(398-958)

365

(282-473)

365

(212-628)

290

(115-727)

13-22 792

(501-1253)

639

(498-820)

541

(323-905)

221

(071-686)

23+ 1112

(660-1870)

853

(635-1150)

901

(504-1610)

637

(210-1930)

P trend lt00001 lt00001 lt00001 00001




of lung cancer





damage





weights



developed world



Obesity

Western diet

Physical inactivity

Smoking







GST enzymes







GSTP1 polymorphism







Smokers














us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang









initiation

Longest duration

before pregnancy

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131)

Al-Delaimy(2004) 129 (097-171) 110 (080-152)

Reynolds (2004) 117 (105-130) 113 (100-125)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137)

Olson (2005) 112 (092-136) 121 (101-125)

Cui (2006) 111 (097-128) 113 (101-125)

Ha (2007) 148 (077-284) 178 (127-249)11

9 of 9 positive

4 of 9 Stat Sig




initiation

Longest duration

before pregnancy

Longest

duration

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189)

Ha (2007) 148 (077-284) 178 (127-249)11

6 of 6 positive

3 of 6 Stat Sig




initiation

Longest duration

Before pregnancy

Longest

duration

Highest pack-

years

Calle (1994) 159 (117-215) 138 (105-183)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133) 125 (106-147)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174) 146 (111-193)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138) 115 (096-137)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189) 117 (102-134)

Ha (2007) 148 (077-284) 178 (127-249)11


5 of 5 positive




First Author Year



Relative Risk

(95 CI)

Reynolds et al (2004) lt20 117 (105-130)

Olson et al (2005) lt19 112 (092-136)

Xue et al (2011) lt18 104 (099-111)

Cui et al (2006) lt16 111 (097-128)


Gram et al (2005) lt15 148 (103-213)

Ha et al (2007) lt15 148 (077-284)



















i
























bull History

bull Lung diseases


bull History

bull Lung disease



TOBACCO SMOKE








INFLAMMATION



LUNG CANCER




ndash COPD

ndash Lung cancer









times








bull History

bull Lung disease












bull History

bull Lung diseases

bull COPD









bull Findings






bull Interpretation







Follow up (y)

Po

stb

ron

cho

dila

tor

FEV

1 L

24

25

26

27

28

29

Screen 2 1 2 3 4 5

Sustained Quitters

Continuous Smokers



COPD










bull Asthma

Asthma








32 subjects


10 quit smoking

Lung cancer













200615517-523















Wen et al--2010




Kolappan Gopi--2002

Thank you




Cancer


Lung

Mouth and pharynx

Larynx

Esophagus

Stomach

Pancreas

Liver

Cervix

Bladder

Kidney

Colorectum

Breast




Body mass index






45-74 years







history from women




51 of the cohort




Heavy smokers (12)


Light smokers (88)





Men (n=27292) Women (n=34028)


Percent 422 214 364 913 25 62


Lung cancer


Never 100

1-12 432 (355-523)

13-22 661 (546-802)

23+ 949 (758-1188)

P for trend lt00001

Smoking status

Lung cancer

RR (95 CI)

Never 100

Former 224 (181-278)

Current 585 (499-687)







Body Mass

Index (kgm2)

Never

smokers

Former

smokers

Current

smokers

Adj HR

(95 CI)

Adj HR

(95 CI)

Adj HR

(95 CI)

lt20 100 100 100

20-lt24 102 (071-146) 092 (057-148) 081 (067-099)

24-lt28 072 (046-110) 101 (059-174) 062 (046-082)

28+ 081 (046-144) 097 (044-212) 050 (028-088)

P for trend 008 089 00001



Smoking

status



Never 100 100 100 100

Former 246

(140-432)

197

(148-262)

296

(184-476)

199

(088-452)

Current 721

(484-1075)

520

(422-641)

550

(364-832)

321

(158-651)





1-12 618

(398-958)

365

(282-473)

365

(212-628)

290

(115-727)

13-22 792

(501-1253)

639

(498-820)

541

(323-905)

221

(071-686)

23+ 1112

(660-1870)

853

(635-1150)

901

(504-1610)

637

(210-1930)

P trend lt00001 lt00001 lt00001 00001




of lung cancer





damage





weights



developed world



Obesity

Western diet

Physical inactivity

Smoking







GST enzymes







GSTP1 polymorphism







Smokers














us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang









initiation

Longest duration

before pregnancy

Longest

duration

Calle (1994) 159 (117-215)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189)

Ha (2007) 148 (077-284) 178 (127-249)11

6 of 6 positive

3 of 6 Stat Sig




initiation

Longest duration

Before pregnancy

Longest

duration

Highest pack-

years

Calle (1994) 159 (117-215) 138 (105-183)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133) 125 (106-147)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174) 146 (111-193)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138) 115 (096-137)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189) 117 (102-134)

Ha (2007) 148 (077-284) 178 (127-249)11


5 of 5 positive




First Author Year



Relative Risk

(95 CI)

Reynolds et al (2004) lt20 117 (105-130)

Olson et al (2005) lt19 112 (092-136)

Xue et al (2011) lt18 104 (099-111)

Cui et al (2006) lt16 111 (097-128)


Gram et al (2005) lt15 148 (103-213)

Ha et al (2007) lt15 148 (077-284)



















i
























bull History

bull Lung diseases


bull History

bull Lung disease



TOBACCO SMOKE








INFLAMMATION



LUNG CANCER




ndash COPD

ndash Lung cancer









times








bull History

bull Lung disease












bull History

bull Lung diseases

bull COPD









bull Findings






bull Interpretation







Follow up (y)

Po

stb

ron

cho

dila

tor

FEV

1 L

24

25

26

27

28

29

Screen 2 1 2 3 4 5

Sustained Quitters

Continuous Smokers



COPD










bull Asthma

Asthma








32 subjects


10 quit smoking

Lung cancer













200615517-523















Wen et al--2010




Kolappan Gopi--2002

Thank you




Cancer


Lung

Mouth and pharynx

Larynx

Esophagus

Stomach

Pancreas

Liver

Cervix

Bladder

Kidney

Colorectum

Breast




Body mass index






45-74 years







history from women




51 of the cohort




Heavy smokers (12)


Light smokers (88)





Men (n=27292) Women (n=34028)


Percent 422 214 364 913 25 62


Lung cancer


Never 100

1-12 432 (355-523)

13-22 661 (546-802)

23+ 949 (758-1188)

P for trend lt00001

Smoking status

Lung cancer

RR (95 CI)

Never 100

Former 224 (181-278)

Current 585 (499-687)







Body Mass

Index (kgm2)

Never

smokers

Former

smokers

Current

smokers

Adj HR

(95 CI)

Adj HR

(95 CI)

Adj HR

(95 CI)

lt20 100 100 100

20-lt24 102 (071-146) 092 (057-148) 081 (067-099)

24-lt28 072 (046-110) 101 (059-174) 062 (046-082)

28+ 081 (046-144) 097 (044-212) 050 (028-088)

P for trend 008 089 00001



Smoking

status



Never 100 100 100 100

Former 246

(140-432)

197

(148-262)

296

(184-476)

199

(088-452)

Current 721

(484-1075)

520

(422-641)

550

(364-832)

321

(158-651)





1-12 618

(398-958)

365

(282-473)

365

(212-628)

290

(115-727)

13-22 792

(501-1253)

639

(498-820)

541

(323-905)

221

(071-686)

23+ 1112

(660-1870)

853

(635-1150)

901

(504-1610)

637

(210-1930)

P trend lt00001 lt00001 lt00001 00001




of lung cancer





damage





weights



developed world



Obesity

Western diet

Physical inactivity

Smoking







GST enzymes







GSTP1 polymorphism







Smokers














us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang









initiation

Longest duration

Before pregnancy

Longest

duration

Highest pack-

years

Calle (1994) 159 (117-215) 138 (105-183)

Egan (2002) 119 (103-137) 113 (099-131) 105 (090-121)

Al-Delaimy(2004) 129 (097-171) 110 (080-152) 121 (101-145)

Reynolds (2004) 117 (105-130) 113 (100-125) 115 (100-133) 125 (106-147)

Lawlor (2004) 106 (072-156)

104 (067 159)

Gram (2005) 148 (103-213) 127 (107-137) 136 (106-174) 146 (111-193)

Olson (2005) 112 (092-136) 121 (101-125) 118 (100-138) 115 (096-137)

Cui (2006) 111 (097-128) 113 (101-125) 150 (119-189) 117 (102-134)

Ha (2007) 148 (077-284) 178 (127-249)11


5 of 5 positive




First Author Year



Relative Risk

(95 CI)

Reynolds et al (2004) lt20 117 (105-130)

Olson et al (2005) lt19 112 (092-136)

Xue et al (2011) lt18 104 (099-111)

Cui et al (2006) lt16 111 (097-128)


Gram et al (2005) lt15 148 (103-213)

Ha et al (2007) lt15 148 (077-284)



















i
























bull History

bull Lung diseases


bull History

bull Lung disease



TOBACCO SMOKE








INFLAMMATION



LUNG CANCER




ndash COPD

ndash Lung cancer









times








bull History

bull Lung disease












bull History

bull Lung diseases

bull COPD









bull Findings






bull Interpretation







Follow up (y)

Po

stb

ron

cho

dila

tor

FEV

1 L

24

25

26

27

28

29

Screen 2 1 2 3 4 5

Sustained Quitters

Continuous Smokers



COPD










bull Asthma

Asthma








32 subjects


10 quit smoking

Lung cancer













200615517-523















Wen et al--2010




Kolappan Gopi--2002

Thank you




Cancer


Lung

Mouth and pharynx

Larynx

Esophagus

Stomach

Pancreas

Liver

Cervix

Bladder

Kidney

Colorectum

Breast




Body mass index






45-74 years







history from women




51 of the cohort




Heavy smokers (12)


Light smokers (88)





Men (n=27292) Women (n=34028)


Percent 422 214 364 913 25 62


Lung cancer


Never 100

1-12 432 (355-523)

13-22 661 (546-802)

23+ 949 (758-1188)

P for trend lt00001

Smoking status

Lung cancer

RR (95 CI)

Never 100

Former 224 (181-278)

Current 585 (499-687)







Body Mass

Index (kgm2)

Never

smokers

Former

smokers

Current

smokers

Adj HR

(95 CI)

Adj HR

(95 CI)

Adj HR

(95 CI)

lt20 100 100 100

20-lt24 102 (071-146) 092 (057-148) 081 (067-099)

24-lt28 072 (046-110) 101 (059-174) 062 (046-082)

28+ 081 (046-144) 097 (044-212) 050 (028-088)

P for trend 008 089 00001



Smoking

status



Never 100 100 100 100

Former 246

(140-432)

197

(148-262)

296

(184-476)

199

(088-452)

Current 721

(484-1075)

520

(422-641)

550

(364-832)

321

(158-651)





1-12 618

(398-958)

365

(282-473)

365

(212-628)

290

(115-727)

13-22 792

(501-1253)

639

(498-820)

541

(323-905)

221

(071-686)

23+ 1112

(660-1870)

853

(635-1150)

901

(504-1610)

637

(210-1930)

P trend lt00001 lt00001 lt00001 00001




of lung cancer





damage





weights



developed world



Obesity

Western diet

Physical inactivity

Smoking







GST enzymes







GSTP1 polymorphism







Smokers














us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang









First Author Year



Relative Risk

(95 CI)

Reynolds et al (2004) lt20 117 (105-130)

Olson et al (2005) lt19 112 (092-136)

Xue et al (2011) lt18 104 (099-111)

Cui et al (2006) lt16 111 (097-128)


Gram et al (2005) lt15 148 (103-213)

Ha et al (2007) lt15 148 (077-284)



















i
























bull History

bull Lung diseases


bull History

bull Lung disease



TOBACCO SMOKE








INFLAMMATION



LUNG CANCER




ndash COPD

ndash Lung cancer









times








bull History

bull Lung disease












bull History

bull Lung diseases

bull COPD









bull Findings






bull Interpretation







Follow up (y)

Po

stb

ron

cho

dila

tor

FEV

1 L

24

25

26

27

28

29

Screen 2 1 2 3 4 5

Sustained Quitters

Continuous Smokers



COPD










bull Asthma

Asthma








32 subjects


10 quit smoking

Lung cancer













200615517-523















Wen et al--2010




Kolappan Gopi--2002

Thank you




Cancer


Lung

Mouth and pharynx

Larynx

Esophagus

Stomach

Pancreas

Liver

Cervix

Bladder

Kidney

Colorectum

Breast




Body mass index






45-74 years







history from women




51 of the cohort




Heavy smokers (12)


Light smokers (88)





Men (n=27292) Women (n=34028)


Percent 422 214 364 913 25 62


Lung cancer


Never 100

1-12 432 (355-523)

13-22 661 (546-802)

23+ 949 (758-1188)

P for trend lt00001

Smoking status

Lung cancer

RR (95 CI)

Never 100

Former 224 (181-278)

Current 585 (499-687)







Body Mass

Index (kgm2)

Never

smokers

Former

smokers

Current

smokers

Adj HR

(95 CI)

Adj HR

(95 CI)

Adj HR

(95 CI)

lt20 100 100 100

20-lt24 102 (071-146) 092 (057-148) 081 (067-099)

24-lt28 072 (046-110) 101 (059-174) 062 (046-082)

28+ 081 (046-144) 097 (044-212) 050 (028-088)

P for trend 008 089 00001



Smoking

status



Never 100 100 100 100

Former 246

(140-432)

197

(148-262)

296

(184-476)

199

(088-452)

Current 721

(484-1075)

520

(422-641)

550

(364-832)

321

(158-651)





1-12 618

(398-958)

365

(282-473)

365

(212-628)

290

(115-727)

13-22 792

(501-1253)

639

(498-820)

541

(323-905)

221

(071-686)

23+ 1112

(660-1870)

853

(635-1150)

901

(504-1610)

637

(210-1930)

P trend lt00001 lt00001 lt00001 00001




of lung cancer





damage





weights



developed world



Obesity

Western diet

Physical inactivity

Smoking







GST enzymes







GSTP1 polymorphism







Smokers














us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang

























i
























bull History

bull Lung diseases


bull History

bull Lung disease



TOBACCO SMOKE








INFLAMMATION



LUNG CANCER




ndash COPD

ndash Lung cancer









times








bull History

bull Lung disease












bull History

bull Lung diseases

bull COPD









bull Findings






bull Interpretation







Follow up (y)

Po

stb

ron

cho

dila

tor

FEV

1 L

24

25

26

27

28

29

Screen 2 1 2 3 4 5

Sustained Quitters

Continuous Smokers



COPD










bull Asthma

Asthma








32 subjects


10 quit smoking

Lung cancer













200615517-523















Wen et al--2010




Kolappan Gopi--2002

Thank you




Cancer


Lung

Mouth and pharynx

Larynx

Esophagus

Stomach

Pancreas

Liver

Cervix

Bladder

Kidney

Colorectum

Breast




Body mass index






45-74 years







history from women




51 of the cohort




Heavy smokers (12)


Light smokers (88)





Men (n=27292) Women (n=34028)


Percent 422 214 364 913 25 62


Lung cancer


Never 100

1-12 432 (355-523)

13-22 661 (546-802)

23+ 949 (758-1188)

P for trend lt00001

Smoking status

Lung cancer

RR (95 CI)

Never 100

Former 224 (181-278)

Current 585 (499-687)







Body Mass

Index (kgm2)

Never

smokers

Former

smokers

Current

smokers

Adj HR

(95 CI)

Adj HR

(95 CI)

Adj HR

(95 CI)

lt20 100 100 100

20-lt24 102 (071-146) 092 (057-148) 081 (067-099)

24-lt28 072 (046-110) 101 (059-174) 062 (046-082)

28+ 081 (046-144) 097 (044-212) 050 (028-088)

P for trend 008 089 00001



Smoking

status



Never 100 100 100 100

Former 246

(140-432)

197

(148-262)

296

(184-476)

199

(088-452)

Current 721

(484-1075)

520

(422-641)

550

(364-832)

321

(158-651)





1-12 618

(398-958)

365

(282-473)

365

(212-628)

290

(115-727)

13-22 792

(501-1253)

639

(498-820)

541

(323-905)

221

(071-686)

23+ 1112

(660-1870)

853

(635-1150)

901

(504-1610)

637

(210-1930)

P trend lt00001 lt00001 lt00001 00001




of lung cancer





damage





weights



developed world



Obesity

Western diet

Physical inactivity

Smoking







GST enzymes







GSTP1 polymorphism







Smokers














us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang




























bull History

bull Lung diseases


bull History

bull Lung disease



TOBACCO SMOKE








INFLAMMATION



LUNG CANCER




ndash COPD

ndash Lung cancer









times








bull History

bull Lung disease












bull History

bull Lung diseases

bull COPD









bull Findings






bull Interpretation







Follow up (y)

Po

stb

ron

cho

dila

tor

FEV

1 L

24

25

26

27

28

29

Screen 2 1 2 3 4 5

Sustained Quitters

Continuous Smokers



COPD










bull Asthma

Asthma








32 subjects


10 quit smoking

Lung cancer













200615517-523















Wen et al--2010




Kolappan Gopi--2002

Thank you




Cancer


Lung

Mouth and pharynx

Larynx

Esophagus

Stomach

Pancreas

Liver

Cervix

Bladder

Kidney

Colorectum

Breast




Body mass index






45-74 years







history from women




51 of the cohort




Heavy smokers (12)


Light smokers (88)





Men (n=27292) Women (n=34028)


Percent 422 214 364 913 25 62


Lung cancer


Never 100

1-12 432 (355-523)

13-22 661 (546-802)

23+ 949 (758-1188)

P for trend lt00001

Smoking status

Lung cancer

RR (95 CI)

Never 100

Former 224 (181-278)

Current 585 (499-687)







Body Mass

Index (kgm2)

Never

smokers

Former

smokers

Current

smokers

Adj HR

(95 CI)

Adj HR

(95 CI)

Adj HR

(95 CI)

lt20 100 100 100

20-lt24 102 (071-146) 092 (057-148) 081 (067-099)

24-lt28 072 (046-110) 101 (059-174) 062 (046-082)

28+ 081 (046-144) 097 (044-212) 050 (028-088)

P for trend 008 089 00001



Smoking

status



Never 100 100 100 100

Former 246

(140-432)

197

(148-262)

296

(184-476)

199

(088-452)

Current 721

(484-1075)

520

(422-641)

550

(364-832)

321

(158-651)





1-12 618

(398-958)

365

(282-473)

365

(212-628)

290

(115-727)

13-22 792

(501-1253)

639

(498-820)

541

(323-905)

221

(071-686)

23+ 1112

(660-1870)

853

(635-1150)

901

(504-1610)

637

(210-1930)

P trend lt00001 lt00001 lt00001 00001




of lung cancer





damage





weights



developed world



Obesity

Western diet

Physical inactivity

Smoking







GST enzymes







GSTP1 polymorphism







Smokers














us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang








bull History

bull Lung disease



TOBACCO SMOKE








INFLAMMATION



LUNG CANCER




ndash COPD

ndash Lung cancer









times








bull History

bull Lung disease












bull History

bull Lung diseases

bull COPD









bull Findings






bull Interpretation







Follow up (y)

Po

stb

ron

cho

dila

tor

FEV

1 L

24

25

26

27

28

29

Screen 2 1 2 3 4 5

Sustained Quitters

Continuous Smokers



COPD










bull Asthma

Asthma








32 subjects


10 quit smoking

Lung cancer













200615517-523















Wen et al--2010




Kolappan Gopi--2002

Thank you




Cancer


Lung

Mouth and pharynx

Larynx

Esophagus

Stomach

Pancreas

Liver

Cervix

Bladder

Kidney

Colorectum

Breast




Body mass index






45-74 years







history from women




51 of the cohort




Heavy smokers (12)


Light smokers (88)





Men (n=27292) Women (n=34028)


Percent 422 214 364 913 25 62


Lung cancer


Never 100

1-12 432 (355-523)

13-22 661 (546-802)

23+ 949 (758-1188)

P for trend lt00001

Smoking status

Lung cancer

RR (95 CI)

Never 100

Former 224 (181-278)

Current 585 (499-687)







Body Mass

Index (kgm2)

Never

smokers

Former

smokers

Current

smokers

Adj HR

(95 CI)

Adj HR

(95 CI)

Adj HR

(95 CI)

lt20 100 100 100

20-lt24 102 (071-146) 092 (057-148) 081 (067-099)

24-lt28 072 (046-110) 101 (059-174) 062 (046-082)

28+ 081 (046-144) 097 (044-212) 050 (028-088)

P for trend 008 089 00001



Smoking

status



Never 100 100 100 100

Former 246

(140-432)

197

(148-262)

296

(184-476)

199

(088-452)

Current 721

(484-1075)

520

(422-641)

550

(364-832)

321

(158-651)





1-12 618

(398-958)

365

(282-473)

365

(212-628)

290

(115-727)

13-22 792

(501-1253)

639

(498-820)

541

(323-905)

221

(071-686)

23+ 1112

(660-1870)

853

(635-1150)

901

(504-1610)

637

(210-1930)

P trend lt00001 lt00001 lt00001 00001




of lung cancer





damage





weights



developed world



Obesity

Western diet

Physical inactivity

Smoking







GST enzymes







GSTP1 polymorphism







Smokers














us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang









TOBACCO SMOKE








INFLAMMATION



LUNG CANCER




ndash COPD

ndash Lung cancer









times








bull History

bull Lung disease












bull History

bull Lung diseases

bull COPD









bull Findings






bull Interpretation







Follow up (y)

Po

stb

ron

cho

dila

tor

FEV

1 L

24

25

26

27

28

29

Screen 2 1 2 3 4 5

Sustained Quitters

Continuous Smokers



COPD










bull Asthma

Asthma








32 subjects


10 quit smoking

Lung cancer













200615517-523















Wen et al--2010




Kolappan Gopi--2002

Thank you




Cancer


Lung

Mouth and pharynx

Larynx

Esophagus

Stomach

Pancreas

Liver

Cervix

Bladder

Kidney

Colorectum

Breast




Body mass index






45-74 years







history from women




51 of the cohort




Heavy smokers (12)


Light smokers (88)





Men (n=27292) Women (n=34028)


Percent 422 214 364 913 25 62


Lung cancer


Never 100

1-12 432 (355-523)

13-22 661 (546-802)

23+ 949 (758-1188)

P for trend lt00001

Smoking status

Lung cancer

RR (95 CI)

Never 100

Former 224 (181-278)

Current 585 (499-687)







Body Mass

Index (kgm2)

Never

smokers

Former

smokers

Current

smokers

Adj HR

(95 CI)

Adj HR

(95 CI)

Adj HR

(95 CI)

lt20 100 100 100

20-lt24 102 (071-146) 092 (057-148) 081 (067-099)

24-lt28 072 (046-110) 101 (059-174) 062 (046-082)

28+ 081 (046-144) 097 (044-212) 050 (028-088)

P for trend 008 089 00001



Smoking

status



Never 100 100 100 100

Former 246

(140-432)

197

(148-262)

296

(184-476)

199

(088-452)

Current 721

(484-1075)

520

(422-641)

550

(364-832)

321

(158-651)





1-12 618

(398-958)

365

(282-473)

365

(212-628)

290

(115-727)

13-22 792

(501-1253)

639

(498-820)

541

(323-905)

221

(071-686)

23+ 1112

(660-1870)

853

(635-1150)

901

(504-1610)

637

(210-1930)

P trend lt00001 lt00001 lt00001 00001




of lung cancer





damage





weights



developed world



Obesity

Western diet

Physical inactivity

Smoking







GST enzymes







GSTP1 polymorphism







Smokers














us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang









ndash COPD

ndash Lung cancer









times








bull History

bull Lung disease












bull History

bull Lung diseases

bull COPD









bull Findings






bull Interpretation







Follow up (y)

Po

stb

ron

cho

dila

tor

FEV

1 L

24

25

26

27

28

29

Screen 2 1 2 3 4 5

Sustained Quitters

Continuous Smokers



COPD










bull Asthma

Asthma








32 subjects


10 quit smoking

Lung cancer













200615517-523















Wen et al--2010




Kolappan Gopi--2002

Thank you




Cancer


Lung

Mouth and pharynx

Larynx

Esophagus

Stomach

Pancreas

Liver

Cervix

Bladder

Kidney

Colorectum

Breast




Body mass index






45-74 years







history from women




51 of the cohort




Heavy smokers (12)


Light smokers (88)





Men (n=27292) Women (n=34028)


Percent 422 214 364 913 25 62


Lung cancer


Never 100

1-12 432 (355-523)

13-22 661 (546-802)

23+ 949 (758-1188)

P for trend lt00001

Smoking status

Lung cancer

RR (95 CI)

Never 100

Former 224 (181-278)

Current 585 (499-687)







Body Mass

Index (kgm2)

Never

smokers

Former

smokers

Current

smokers

Adj HR

(95 CI)

Adj HR

(95 CI)

Adj HR

(95 CI)

lt20 100 100 100

20-lt24 102 (071-146) 092 (057-148) 081 (067-099)

24-lt28 072 (046-110) 101 (059-174) 062 (046-082)

28+ 081 (046-144) 097 (044-212) 050 (028-088)

P for trend 008 089 00001



Smoking

status



Never 100 100 100 100

Former 246

(140-432)

197

(148-262)

296

(184-476)

199

(088-452)

Current 721

(484-1075)

520

(422-641)

550

(364-832)

321

(158-651)





1-12 618

(398-958)

365

(282-473)

365

(212-628)

290

(115-727)

13-22 792

(501-1253)

639

(498-820)

541

(323-905)

221

(071-686)

23+ 1112

(660-1870)

853

(635-1150)

901

(504-1610)

637

(210-1930)

P trend lt00001 lt00001 lt00001 00001




of lung cancer





damage





weights



developed world



Obesity

Western diet

Physical inactivity

Smoking







GST enzymes







GSTP1 polymorphism







Smokers














us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang















times








bull History

bull Lung disease












bull History

bull Lung diseases

bull COPD









bull Findings






bull Interpretation







Follow up (y)

Po

stb

ron

cho

dila

tor

FEV

1 L

24

25

26

27

28

29

Screen 2 1 2 3 4 5

Sustained Quitters

Continuous Smokers



COPD










bull Asthma

Asthma








32 subjects


10 quit smoking

Lung cancer













200615517-523















Wen et al--2010




Kolappan Gopi--2002

Thank you




Cancer


Lung

Mouth and pharynx

Larynx

Esophagus

Stomach

Pancreas

Liver

Cervix

Bladder

Kidney

Colorectum

Breast




Body mass index






45-74 years







history from women




51 of the cohort




Heavy smokers (12)


Light smokers (88)





Men (n=27292) Women (n=34028)


Percent 422 214 364 913 25 62


Lung cancer


Never 100

1-12 432 (355-523)

13-22 661 (546-802)

23+ 949 (758-1188)

P for trend lt00001

Smoking status

Lung cancer

RR (95 CI)

Never 100

Former 224 (181-278)

Current 585 (499-687)







Body Mass

Index (kgm2)

Never

smokers

Former

smokers

Current

smokers

Adj HR

(95 CI)

Adj HR

(95 CI)

Adj HR

(95 CI)

lt20 100 100 100

20-lt24 102 (071-146) 092 (057-148) 081 (067-099)

24-lt28 072 (046-110) 101 (059-174) 062 (046-082)

28+ 081 (046-144) 097 (044-212) 050 (028-088)

P for trend 008 089 00001



Smoking

status



Never 100 100 100 100

Former 246

(140-432)

197

(148-262)

296

(184-476)

199

(088-452)

Current 721

(484-1075)

520

(422-641)

550

(364-832)

321

(158-651)





1-12 618

(398-958)

365

(282-473)

365

(212-628)

290

(115-727)

13-22 792

(501-1253)

639

(498-820)

541

(323-905)

221

(071-686)

23+ 1112

(660-1870)

853

(635-1150)

901

(504-1610)

637

(210-1930)

P trend lt00001 lt00001 lt00001 00001




of lung cancer





damage





weights



developed world



Obesity

Western diet

Physical inactivity

Smoking







GST enzymes







GSTP1 polymorphism







Smokers














us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang














bull History

bull Lung disease












bull History

bull Lung diseases

bull COPD









bull Findings






bull Interpretation







Follow up (y)

Po

stb

ron

cho

dila

tor

FEV

1 L

24

25

26

27

28

29

Screen 2 1 2 3 4 5

Sustained Quitters

Continuous Smokers



COPD










bull Asthma

Asthma








32 subjects


10 quit smoking

Lung cancer













200615517-523















Wen et al--2010




Kolappan Gopi--2002

Thank you




Cancer


Lung

Mouth and pharynx

Larynx

Esophagus

Stomach

Pancreas

Liver

Cervix

Bladder

Kidney

Colorectum

Breast




Body mass index






45-74 years







history from women




51 of the cohort




Heavy smokers (12)


Light smokers (88)





Men (n=27292) Women (n=34028)


Percent 422 214 364 913 25 62


Lung cancer


Never 100

1-12 432 (355-523)

13-22 661 (546-802)

23+ 949 (758-1188)

P for trend lt00001

Smoking status

Lung cancer

RR (95 CI)

Never 100

Former 224 (181-278)

Current 585 (499-687)







Body Mass

Index (kgm2)

Never

smokers

Former

smokers

Current

smokers

Adj HR

(95 CI)

Adj HR

(95 CI)

Adj HR

(95 CI)

lt20 100 100 100

20-lt24 102 (071-146) 092 (057-148) 081 (067-099)

24-lt28 072 (046-110) 101 (059-174) 062 (046-082)

28+ 081 (046-144) 097 (044-212) 050 (028-088)

P for trend 008 089 00001



Smoking

status



Never 100 100 100 100

Former 246

(140-432)

197

(148-262)

296

(184-476)

199

(088-452)

Current 721

(484-1075)

520

(422-641)

550

(364-832)

321

(158-651)





1-12 618

(398-958)

365

(282-473)

365

(212-628)

290

(115-727)

13-22 792

(501-1253)

639

(498-820)

541

(323-905)

221

(071-686)

23+ 1112

(660-1870)

853

(635-1150)

901

(504-1610)

637

(210-1930)

P trend lt00001 lt00001 lt00001 00001




of lung cancer





damage





weights



developed world



Obesity

Western diet

Physical inactivity

Smoking







GST enzymes







GSTP1 polymorphism







Smokers














us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang


















bull History

bull Lung diseases

bull COPD









bull Findings






bull Interpretation







Follow up (y)

Po

stb

ron

cho

dila

tor

FEV

1 L

24

25

26

27

28

29

Screen 2 1 2 3 4 5

Sustained Quitters

Continuous Smokers



COPD










bull Asthma

Asthma








32 subjects


10 quit smoking

Lung cancer













200615517-523















Wen et al--2010




Kolappan Gopi--2002

Thank you




Cancer


Lung

Mouth and pharynx

Larynx

Esophagus

Stomach

Pancreas

Liver

Cervix

Bladder

Kidney

Colorectum

Breast




Body mass index






45-74 years







history from women




51 of the cohort




Heavy smokers (12)


Light smokers (88)





Men (n=27292) Women (n=34028)


Percent 422 214 364 913 25 62


Lung cancer


Never 100

1-12 432 (355-523)

13-22 661 (546-802)

23+ 949 (758-1188)

P for trend lt00001

Smoking status

Lung cancer

RR (95 CI)

Never 100

Former 224 (181-278)

Current 585 (499-687)







Body Mass

Index (kgm2)

Never

smokers

Former

smokers

Current

smokers

Adj HR

(95 CI)

Adj HR

(95 CI)

Adj HR

(95 CI)

lt20 100 100 100

20-lt24 102 (071-146) 092 (057-148) 081 (067-099)

24-lt28 072 (046-110) 101 (059-174) 062 (046-082)

28+ 081 (046-144) 097 (044-212) 050 (028-088)

P for trend 008 089 00001



Smoking

status



Never 100 100 100 100

Former 246

(140-432)

197

(148-262)

296

(184-476)

199

(088-452)

Current 721

(484-1075)

520

(422-641)

550

(364-832)

321

(158-651)





1-12 618

(398-958)

365

(282-473)

365

(212-628)

290

(115-727)

13-22 792

(501-1253)

639

(498-820)

541

(323-905)

221

(071-686)

23+ 1112

(660-1870)

853

(635-1150)

901

(504-1610)

637

(210-1930)

P trend lt00001 lt00001 lt00001 00001




of lung cancer





damage





weights



developed world



Obesity

Western diet

Physical inactivity

Smoking







GST enzymes







GSTP1 polymorphism







Smokers














us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang







bull COPD









bull Findings






bull Interpretation







Follow up (y)

Po

stb

ron

cho

dila

tor

FEV

1 L

24

25

26

27

28

29

Screen 2 1 2 3 4 5

Sustained Quitters

Continuous Smokers



COPD










bull Asthma

Asthma








32 subjects


10 quit smoking

Lung cancer













200615517-523















Wen et al--2010




Kolappan Gopi--2002

Thank you




Cancer


Lung

Mouth and pharynx

Larynx

Esophagus

Stomach

Pancreas

Liver

Cervix

Bladder

Kidney

Colorectum

Breast




Body mass index






45-74 years







history from women




51 of the cohort




Heavy smokers (12)


Light smokers (88)





Men (n=27292) Women (n=34028)


Percent 422 214 364 913 25 62


Lung cancer


Never 100

1-12 432 (355-523)

13-22 661 (546-802)

23+ 949 (758-1188)

P for trend lt00001

Smoking status

Lung cancer

RR (95 CI)

Never 100

Former 224 (181-278)

Current 585 (499-687)







Body Mass

Index (kgm2)

Never

smokers

Former

smokers

Current

smokers

Adj HR

(95 CI)

Adj HR

(95 CI)

Adj HR

(95 CI)

lt20 100 100 100

20-lt24 102 (071-146) 092 (057-148) 081 (067-099)

24-lt28 072 (046-110) 101 (059-174) 062 (046-082)

28+ 081 (046-144) 097 (044-212) 050 (028-088)

P for trend 008 089 00001



Smoking

status



Never 100 100 100 100

Former 246

(140-432)

197

(148-262)

296

(184-476)

199

(088-452)

Current 721

(484-1075)

520

(422-641)

550

(364-832)

321

(158-651)





1-12 618

(398-958)

365

(282-473)

365

(212-628)

290

(115-727)

13-22 792

(501-1253)

639

(498-820)

541

(323-905)

221

(071-686)

23+ 1112

(660-1870)

853

(635-1150)

901

(504-1610)

637

(210-1930)

P trend lt00001 lt00001 lt00001 00001




of lung cancer





damage





weights



developed world



Obesity

Western diet

Physical inactivity

Smoking







GST enzymes







GSTP1 polymorphism







Smokers














us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang















bull Findings






bull Interpretation







Follow up (y)

Po

stb

ron

cho

dila

tor

FEV

1 L

24

25

26

27

28

29

Screen 2 1 2 3 4 5

Sustained Quitters

Continuous Smokers



COPD










bull Asthma

Asthma








32 subjects


10 quit smoking

Lung cancer













200615517-523















Wen et al--2010




Kolappan Gopi--2002

Thank you




Cancer


Lung

Mouth and pharynx

Larynx

Esophagus

Stomach

Pancreas

Liver

Cervix

Bladder

Kidney

Colorectum

Breast




Body mass index






45-74 years







history from women




51 of the cohort




Heavy smokers (12)


Light smokers (88)





Men (n=27292) Women (n=34028)


Percent 422 214 364 913 25 62


Lung cancer


Never 100

1-12 432 (355-523)

13-22 661 (546-802)

23+ 949 (758-1188)

P for trend lt00001

Smoking status

Lung cancer

RR (95 CI)

Never 100

Former 224 (181-278)

Current 585 (499-687)







Body Mass

Index (kgm2)

Never

smokers

Former

smokers

Current

smokers

Adj HR

(95 CI)

Adj HR

(95 CI)

Adj HR

(95 CI)

lt20 100 100 100

20-lt24 102 (071-146) 092 (057-148) 081 (067-099)

24-lt28 072 (046-110) 101 (059-174) 062 (046-082)

28+ 081 (046-144) 097 (044-212) 050 (028-088)

P for trend 008 089 00001



Smoking

status



Never 100 100 100 100

Former 246

(140-432)

197

(148-262)

296

(184-476)

199

(088-452)

Current 721

(484-1075)

520

(422-641)

550

(364-832)

321

(158-651)





1-12 618

(398-958)

365

(282-473)

365

(212-628)

290

(115-727)

13-22 792

(501-1253)

639

(498-820)

541

(323-905)

221

(071-686)

23+ 1112

(660-1870)

853

(635-1150)

901

(504-1610)

637

(210-1930)

P trend lt00001 lt00001 lt00001 00001




of lung cancer





damage





weights



developed world



Obesity

Western diet

Physical inactivity

Smoking







GST enzymes







GSTP1 polymorphism







Smokers














us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang










Follow up (y)

Po

stb

ron

cho

dila

tor

FEV

1 L

24

25

26

27

28

29

Screen 2 1 2 3 4 5

Sustained Quitters

Continuous Smokers



COPD










bull Asthma

Asthma








32 subjects


10 quit smoking

Lung cancer













200615517-523















Wen et al--2010




Kolappan Gopi--2002

Thank you




Cancer


Lung

Mouth and pharynx

Larynx

Esophagus

Stomach

Pancreas

Liver

Cervix

Bladder

Kidney

Colorectum

Breast




Body mass index






45-74 years







history from women




51 of the cohort




Heavy smokers (12)


Light smokers (88)





Men (n=27292) Women (n=34028)


Percent 422 214 364 913 25 62


Lung cancer


Never 100

1-12 432 (355-523)

13-22 661 (546-802)

23+ 949 (758-1188)

P for trend lt00001

Smoking status

Lung cancer

RR (95 CI)

Never 100

Former 224 (181-278)

Current 585 (499-687)







Body Mass

Index (kgm2)

Never

smokers

Former

smokers

Current

smokers

Adj HR

(95 CI)

Adj HR

(95 CI)

Adj HR

(95 CI)

lt20 100 100 100

20-lt24 102 (071-146) 092 (057-148) 081 (067-099)

24-lt28 072 (046-110) 101 (059-174) 062 (046-082)

28+ 081 (046-144) 097 (044-212) 050 (028-088)

P for trend 008 089 00001



Smoking

status



Never 100 100 100 100

Former 246

(140-432)

197

(148-262)

296

(184-476)

199

(088-452)

Current 721

(484-1075)

520

(422-641)

550

(364-832)

321

(158-651)





1-12 618

(398-958)

365

(282-473)

365

(212-628)

290

(115-727)

13-22 792

(501-1253)

639

(498-820)

541

(323-905)

221

(071-686)

23+ 1112

(660-1870)

853

(635-1150)

901

(504-1610)

637

(210-1930)

P trend lt00001 lt00001 lt00001 00001




of lung cancer





damage





weights



developed world



Obesity

Western diet

Physical inactivity

Smoking







GST enzymes







GSTP1 polymorphism







Smokers














us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang







COPD










bull Asthma

Asthma








32 subjects


10 quit smoking

Lung cancer













200615517-523















Wen et al--2010




Kolappan Gopi--2002

Thank you




Cancer


Lung

Mouth and pharynx

Larynx

Esophagus

Stomach

Pancreas

Liver

Cervix

Bladder

Kidney

Colorectum

Breast




Body mass index






45-74 years







history from women




51 of the cohort




Heavy smokers (12)


Light smokers (88)





Men (n=27292) Women (n=34028)


Percent 422 214 364 913 25 62


Lung cancer


Never 100

1-12 432 (355-523)

13-22 661 (546-802)

23+ 949 (758-1188)

P for trend lt00001

Smoking status

Lung cancer

RR (95 CI)

Never 100

Former 224 (181-278)

Current 585 (499-687)







Body Mass

Index (kgm2)

Never

smokers

Former

smokers

Current

smokers

Adj HR

(95 CI)

Adj HR

(95 CI)

Adj HR

(95 CI)

lt20 100 100 100

20-lt24 102 (071-146) 092 (057-148) 081 (067-099)

24-lt28 072 (046-110) 101 (059-174) 062 (046-082)

28+ 081 (046-144) 097 (044-212) 050 (028-088)

P for trend 008 089 00001



Smoking

status



Never 100 100 100 100

Former 246

(140-432)

197

(148-262)

296

(184-476)

199

(088-452)

Current 721

(484-1075)

520

(422-641)

550

(364-832)

321

(158-651)





1-12 618

(398-958)

365

(282-473)

365

(212-628)

290

(115-727)

13-22 792

(501-1253)

639

(498-820)

541

(323-905)

221

(071-686)

23+ 1112

(660-1870)

853

(635-1150)

901

(504-1610)

637

(210-1930)

P trend lt00001 lt00001 lt00001 00001




of lung cancer





damage





weights



developed world



Obesity

Western diet

Physical inactivity

Smoking







GST enzymes







GSTP1 polymorphism







Smokers














us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang











bull Asthma

Asthma








32 subjects


10 quit smoking

Lung cancer













200615517-523















Wen et al--2010




Kolappan Gopi--2002

Thank you




Cancer


Lung

Mouth and pharynx

Larynx

Esophagus

Stomach

Pancreas

Liver

Cervix

Bladder

Kidney

Colorectum

Breast




Body mass index






45-74 years







history from women




51 of the cohort




Heavy smokers (12)


Light smokers (88)





Men (n=27292) Women (n=34028)


Percent 422 214 364 913 25 62


Lung cancer


Never 100

1-12 432 (355-523)

13-22 661 (546-802)

23+ 949 (758-1188)

P for trend lt00001

Smoking status

Lung cancer

RR (95 CI)

Never 100

Former 224 (181-278)

Current 585 (499-687)







Body Mass

Index (kgm2)

Never

smokers

Former

smokers

Current

smokers

Adj HR

(95 CI)

Adj HR

(95 CI)

Adj HR

(95 CI)

lt20 100 100 100

20-lt24 102 (071-146) 092 (057-148) 081 (067-099)

24-lt28 072 (046-110) 101 (059-174) 062 (046-082)

28+ 081 (046-144) 097 (044-212) 050 (028-088)

P for trend 008 089 00001



Smoking

status



Never 100 100 100 100

Former 246

(140-432)

197

(148-262)

296

(184-476)

199

(088-452)

Current 721

(484-1075)

520

(422-641)

550

(364-832)

321

(158-651)





1-12 618

(398-958)

365

(282-473)

365

(212-628)

290

(115-727)

13-22 792

(501-1253)

639

(498-820)

541

(323-905)

221

(071-686)

23+ 1112

(660-1870)

853

(635-1150)

901

(504-1610)

637

(210-1930)

P trend lt00001 lt00001 lt00001 00001




of lung cancer





damage





weights



developed world



Obesity

Western diet

Physical inactivity

Smoking







GST enzymes







GSTP1 polymorphism







Smokers














us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang







Asthma








32 subjects


10 quit smoking

Lung cancer













200615517-523















Wen et al--2010




Kolappan Gopi--2002

Thank you




Cancer


Lung

Mouth and pharynx

Larynx

Esophagus

Stomach

Pancreas

Liver

Cervix

Bladder

Kidney

Colorectum

Breast




Body mass index






45-74 years







history from women




51 of the cohort




Heavy smokers (12)


Light smokers (88)





Men (n=27292) Women (n=34028)


Percent 422 214 364 913 25 62


Lung cancer


Never 100

1-12 432 (355-523)

13-22 661 (546-802)

23+ 949 (758-1188)

P for trend lt00001

Smoking status

Lung cancer

RR (95 CI)

Never 100

Former 224 (181-278)

Current 585 (499-687)







Body Mass

Index (kgm2)

Never

smokers

Former

smokers

Current

smokers

Adj HR

(95 CI)

Adj HR

(95 CI)

Adj HR

(95 CI)

lt20 100 100 100

20-lt24 102 (071-146) 092 (057-148) 081 (067-099)

24-lt28 072 (046-110) 101 (059-174) 062 (046-082)

28+ 081 (046-144) 097 (044-212) 050 (028-088)

P for trend 008 089 00001



Smoking

status



Never 100 100 100 100

Former 246

(140-432)

197

(148-262)

296

(184-476)

199

(088-452)

Current 721

(484-1075)

520

(422-641)

550

(364-832)

321

(158-651)





1-12 618

(398-958)

365

(282-473)

365

(212-628)

290

(115-727)

13-22 792

(501-1253)

639

(498-820)

541

(323-905)

221

(071-686)

23+ 1112

(660-1870)

853

(635-1150)

901

(504-1610)

637

(210-1930)

P trend lt00001 lt00001 lt00001 00001




of lung cancer





damage





weights



developed world



Obesity

Western diet

Physical inactivity

Smoking







GST enzymes







GSTP1 polymorphism







Smokers














us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang








32 subjects


10 quit smoking

Lung cancer













200615517-523















Wen et al--2010




Kolappan Gopi--2002

Thank you




Cancer


Lung

Mouth and pharynx

Larynx

Esophagus

Stomach

Pancreas

Liver

Cervix

Bladder

Kidney

Colorectum

Breast




Body mass index






45-74 years







history from women




51 of the cohort




Heavy smokers (12)


Light smokers (88)





Men (n=27292) Women (n=34028)


Percent 422 214 364 913 25 62


Lung cancer


Never 100

1-12 432 (355-523)

13-22 661 (546-802)

23+ 949 (758-1188)

P for trend lt00001

Smoking status

Lung cancer

RR (95 CI)

Never 100

Former 224 (181-278)

Current 585 (499-687)







Body Mass

Index (kgm2)

Never

smokers

Former

smokers

Current

smokers

Adj HR

(95 CI)

Adj HR

(95 CI)

Adj HR

(95 CI)

lt20 100 100 100

20-lt24 102 (071-146) 092 (057-148) 081 (067-099)

24-lt28 072 (046-110) 101 (059-174) 062 (046-082)

28+ 081 (046-144) 097 (044-212) 050 (028-088)

P for trend 008 089 00001



Smoking

status



Never 100 100 100 100

Former 246

(140-432)

197

(148-262)

296

(184-476)

199

(088-452)

Current 721

(484-1075)

520

(422-641)

550

(364-832)

321

(158-651)





1-12 618

(398-958)

365

(282-473)

365

(212-628)

290

(115-727)

13-22 792

(501-1253)

639

(498-820)

541

(323-905)

221

(071-686)

23+ 1112

(660-1870)

853

(635-1150)

901

(504-1610)

637

(210-1930)

P trend lt00001 lt00001 lt00001 00001




of lung cancer





damage





weights



developed world



Obesity

Western diet

Physical inactivity

Smoking







GST enzymes







GSTP1 polymorphism







Smokers














us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang







Lung cancer













200615517-523















Wen et al--2010




Kolappan Gopi--2002

Thank you




Cancer


Lung

Mouth and pharynx

Larynx

Esophagus

Stomach

Pancreas

Liver

Cervix

Bladder

Kidney

Colorectum

Breast




Body mass index






45-74 years







history from women




51 of the cohort




Heavy smokers (12)


Light smokers (88)





Men (n=27292) Women (n=34028)


Percent 422 214 364 913 25 62


Lung cancer


Never 100

1-12 432 (355-523)

13-22 661 (546-802)

23+ 949 (758-1188)

P for trend lt00001

Smoking status

Lung cancer

RR (95 CI)

Never 100

Former 224 (181-278)

Current 585 (499-687)







Body Mass

Index (kgm2)

Never

smokers

Former

smokers

Current

smokers

Adj HR

(95 CI)

Adj HR

(95 CI)

Adj HR

(95 CI)

lt20 100 100 100

20-lt24 102 (071-146) 092 (057-148) 081 (067-099)

24-lt28 072 (046-110) 101 (059-174) 062 (046-082)

28+ 081 (046-144) 097 (044-212) 050 (028-088)

P for trend 008 089 00001



Smoking

status



Never 100 100 100 100

Former 246

(140-432)

197

(148-262)

296

(184-476)

199

(088-452)

Current 721

(484-1075)

520

(422-641)

550

(364-832)

321

(158-651)





1-12 618

(398-958)

365

(282-473)

365

(212-628)

290

(115-727)

13-22 792

(501-1253)

639

(498-820)

541

(323-905)

221

(071-686)

23+ 1112

(660-1870)

853

(635-1150)

901

(504-1610)

637

(210-1930)

P trend lt00001 lt00001 lt00001 00001




of lung cancer





damage





weights



developed world



Obesity

Western diet

Physical inactivity

Smoking







GST enzymes







GSTP1 polymorphism







Smokers














us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang



















200615517-523















Wen et al--2010




Kolappan Gopi--2002

Thank you




Cancer


Lung

Mouth and pharynx

Larynx

Esophagus

Stomach

Pancreas

Liver

Cervix

Bladder

Kidney

Colorectum

Breast




Body mass index






45-74 years







history from women




51 of the cohort




Heavy smokers (12)


Light smokers (88)





Men (n=27292) Women (n=34028)


Percent 422 214 364 913 25 62


Lung cancer


Never 100

1-12 432 (355-523)

13-22 661 (546-802)

23+ 949 (758-1188)

P for trend lt00001

Smoking status

Lung cancer

RR (95 CI)

Never 100

Former 224 (181-278)

Current 585 (499-687)







Body Mass

Index (kgm2)

Never

smokers

Former

smokers

Current

smokers

Adj HR

(95 CI)

Adj HR

(95 CI)

Adj HR

(95 CI)

lt20 100 100 100

20-lt24 102 (071-146) 092 (057-148) 081 (067-099)

24-lt28 072 (046-110) 101 (059-174) 062 (046-082)

28+ 081 (046-144) 097 (044-212) 050 (028-088)

P for trend 008 089 00001



Smoking

status



Never 100 100 100 100

Former 246

(140-432)

197

(148-262)

296

(184-476)

199

(088-452)

Current 721

(484-1075)

520

(422-641)

550

(364-832)

321

(158-651)





1-12 618

(398-958)

365

(282-473)

365

(212-628)

290

(115-727)

13-22 792

(501-1253)

639

(498-820)

541

(323-905)

221

(071-686)

23+ 1112

(660-1870)

853

(635-1150)

901

(504-1610)

637

(210-1930)

P trend lt00001 lt00001 lt00001 00001




of lung cancer





damage





weights



developed world



Obesity

Western diet

Physical inactivity

Smoking







GST enzymes







GSTP1 polymorphism







Smokers














us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang





















Wen et al--2010




Kolappan Gopi--2002

Thank you




Cancer


Lung

Mouth and pharynx

Larynx

Esophagus

Stomach

Pancreas

Liver

Cervix

Bladder

Kidney

Colorectum

Breast




Body mass index






45-74 years







history from women




51 of the cohort




Heavy smokers (12)


Light smokers (88)





Men (n=27292) Women (n=34028)


Percent 422 214 364 913 25 62


Lung cancer


Never 100

1-12 432 (355-523)

13-22 661 (546-802)

23+ 949 (758-1188)

P for trend lt00001

Smoking status

Lung cancer

RR (95 CI)

Never 100

Former 224 (181-278)

Current 585 (499-687)







Body Mass

Index (kgm2)

Never

smokers

Former

smokers

Current

smokers

Adj HR

(95 CI)

Adj HR

(95 CI)

Adj HR

(95 CI)

lt20 100 100 100

20-lt24 102 (071-146) 092 (057-148) 081 (067-099)

24-lt28 072 (046-110) 101 (059-174) 062 (046-082)

28+ 081 (046-144) 097 (044-212) 050 (028-088)

P for trend 008 089 00001



Smoking

status



Never 100 100 100 100

Former 246

(140-432)

197

(148-262)

296

(184-476)

199

(088-452)

Current 721

(484-1075)

520

(422-641)

550

(364-832)

321

(158-651)





1-12 618

(398-958)

365

(282-473)

365

(212-628)

290

(115-727)

13-22 792

(501-1253)

639

(498-820)

541

(323-905)

221

(071-686)

23+ 1112

(660-1870)

853

(635-1150)

901

(504-1610)

637

(210-1930)

P trend lt00001 lt00001 lt00001 00001




of lung cancer





damage





weights



developed world



Obesity

Western diet

Physical inactivity

Smoking







GST enzymes







GSTP1 polymorphism







Smokers














us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang










Kolappan Gopi--2002

Thank you




Cancer


Lung

Mouth and pharynx

Larynx

Esophagus

Stomach

Pancreas

Liver

Cervix

Bladder

Kidney

Colorectum

Breast




Body mass index






45-74 years







history from women




51 of the cohort




Heavy smokers (12)


Light smokers (88)





Men (n=27292) Women (n=34028)


Percent 422 214 364 913 25 62


Lung cancer


Never 100

1-12 432 (355-523)

13-22 661 (546-802)

23+ 949 (758-1188)

P for trend lt00001

Smoking status

Lung cancer

RR (95 CI)

Never 100

Former 224 (181-278)

Current 585 (499-687)







Body Mass

Index (kgm2)

Never

smokers

Former

smokers

Current

smokers

Adj HR

(95 CI)

Adj HR

(95 CI)

Adj HR

(95 CI)

lt20 100 100 100

20-lt24 102 (071-146) 092 (057-148) 081 (067-099)

24-lt28 072 (046-110) 101 (059-174) 062 (046-082)

28+ 081 (046-144) 097 (044-212) 050 (028-088)

P for trend 008 089 00001



Smoking

status



Never 100 100 100 100

Former 246

(140-432)

197

(148-262)

296

(184-476)

199

(088-452)

Current 721

(484-1075)

520

(422-641)

550

(364-832)

321

(158-651)





1-12 618

(398-958)

365

(282-473)

365

(212-628)

290

(115-727)

13-22 792

(501-1253)

639

(498-820)

541

(323-905)

221

(071-686)

23+ 1112

(660-1870)

853

(635-1150)

901

(504-1610)

637

(210-1930)

P trend lt00001 lt00001 lt00001 00001




of lung cancer





damage





weights



developed world



Obesity

Western diet

Physical inactivity

Smoking







GST enzymes







GSTP1 polymorphism







Smokers














us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang







Thank you




Cancer


Lung

Mouth and pharynx

Larynx

Esophagus

Stomach

Pancreas

Liver

Cervix

Bladder

Kidney

Colorectum

Breast




Body mass index






45-74 years







history from women




51 of the cohort




Heavy smokers (12)


Light smokers (88)





Men (n=27292) Women (n=34028)


Percent 422 214 364 913 25 62


Lung cancer


Never 100

1-12 432 (355-523)

13-22 661 (546-802)

23+ 949 (758-1188)

P for trend lt00001

Smoking status

Lung cancer

RR (95 CI)

Never 100

Former 224 (181-278)

Current 585 (499-687)







Body Mass

Index (kgm2)

Never

smokers

Former

smokers

Current

smokers

Adj HR

(95 CI)

Adj HR

(95 CI)

Adj HR

(95 CI)

lt20 100 100 100

20-lt24 102 (071-146) 092 (057-148) 081 (067-099)

24-lt28 072 (046-110) 101 (059-174) 062 (046-082)

28+ 081 (046-144) 097 (044-212) 050 (028-088)

P for trend 008 089 00001



Smoking

status



Never 100 100 100 100

Former 246

(140-432)

197

(148-262)

296

(184-476)

199

(088-452)

Current 721

(484-1075)

520

(422-641)

550

(364-832)

321

(158-651)





1-12 618

(398-958)

365

(282-473)

365

(212-628)

290

(115-727)

13-22 792

(501-1253)

639

(498-820)

541

(323-905)

221

(071-686)

23+ 1112

(660-1870)

853

(635-1150)

901

(504-1610)

637

(210-1930)

P trend lt00001 lt00001 lt00001 00001




of lung cancer





damage





weights



developed world



Obesity

Western diet

Physical inactivity

Smoking







GST enzymes







GSTP1 polymorphism







Smokers














us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang










Cancer


Lung

Mouth and pharynx

Larynx

Esophagus

Stomach

Pancreas

Liver

Cervix

Bladder

Kidney

Colorectum

Breast




Body mass index






45-74 years







history from women




51 of the cohort




Heavy smokers (12)


Light smokers (88)





Men (n=27292) Women (n=34028)


Percent 422 214 364 913 25 62


Lung cancer


Never 100

1-12 432 (355-523)

13-22 661 (546-802)

23+ 949 (758-1188)

P for trend lt00001

Smoking status

Lung cancer

RR (95 CI)

Never 100

Former 224 (181-278)

Current 585 (499-687)







Body Mass

Index (kgm2)

Never

smokers

Former

smokers

Current

smokers

Adj HR

(95 CI)

Adj HR

(95 CI)

Adj HR

(95 CI)

lt20 100 100 100

20-lt24 102 (071-146) 092 (057-148) 081 (067-099)

24-lt28 072 (046-110) 101 (059-174) 062 (046-082)

28+ 081 (046-144) 097 (044-212) 050 (028-088)

P for trend 008 089 00001



Smoking

status



Never 100 100 100 100

Former 246

(140-432)

197

(148-262)

296

(184-476)

199

(088-452)

Current 721

(484-1075)

520

(422-641)

550

(364-832)

321

(158-651)





1-12 618

(398-958)

365

(282-473)

365

(212-628)

290

(115-727)

13-22 792

(501-1253)

639

(498-820)

541

(323-905)

221

(071-686)

23+ 1112

(660-1870)

853

(635-1150)

901

(504-1610)

637

(210-1930)

P trend lt00001 lt00001 lt00001 00001




of lung cancer





damage





weights



developed world



Obesity

Western diet

Physical inactivity

Smoking







GST enzymes







GSTP1 polymorphism







Smokers














us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang








Lung

Mouth and pharynx

Larynx

Esophagus

Stomach

Pancreas

Liver

Cervix

Bladder

Kidney

Colorectum

Breast




Body mass index






45-74 years







history from women




51 of the cohort




Heavy smokers (12)


Light smokers (88)





Men (n=27292) Women (n=34028)


Percent 422 214 364 913 25 62


Lung cancer


Never 100

1-12 432 (355-523)

13-22 661 (546-802)

23+ 949 (758-1188)

P for trend lt00001

Smoking status

Lung cancer

RR (95 CI)

Never 100

Former 224 (181-278)

Current 585 (499-687)







Body Mass

Index (kgm2)

Never

smokers

Former

smokers

Current

smokers

Adj HR

(95 CI)

Adj HR

(95 CI)

Adj HR

(95 CI)

lt20 100 100 100

20-lt24 102 (071-146) 092 (057-148) 081 (067-099)

24-lt28 072 (046-110) 101 (059-174) 062 (046-082)

28+ 081 (046-144) 097 (044-212) 050 (028-088)

P for trend 008 089 00001



Smoking

status



Never 100 100 100 100

Former 246

(140-432)

197

(148-262)

296

(184-476)

199

(088-452)

Current 721

(484-1075)

520

(422-641)

550

(364-832)

321

(158-651)





1-12 618

(398-958)

365

(282-473)

365

(212-628)

290

(115-727)

13-22 792

(501-1253)

639

(498-820)

541

(323-905)

221

(071-686)

23+ 1112

(660-1870)

853

(635-1150)

901

(504-1610)

637

(210-1930)

P trend lt00001 lt00001 lt00001 00001




of lung cancer





damage





weights



developed world



Obesity

Western diet

Physical inactivity

Smoking







GST enzymes







GSTP1 polymorphism







Smokers














us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang










Body mass index






45-74 years







history from women




51 of the cohort




Heavy smokers (12)


Light smokers (88)





Men (n=27292) Women (n=34028)


Percent 422 214 364 913 25 62


Lung cancer


Never 100

1-12 432 (355-523)

13-22 661 (546-802)

23+ 949 (758-1188)

P for trend lt00001

Smoking status

Lung cancer

RR (95 CI)

Never 100

Former 224 (181-278)

Current 585 (499-687)







Body Mass

Index (kgm2)

Never

smokers

Former

smokers

Current

smokers

Adj HR

(95 CI)

Adj HR

(95 CI)

Adj HR

(95 CI)

lt20 100 100 100

20-lt24 102 (071-146) 092 (057-148) 081 (067-099)

24-lt28 072 (046-110) 101 (059-174) 062 (046-082)

28+ 081 (046-144) 097 (044-212) 050 (028-088)

P for trend 008 089 00001



Smoking

status



Never 100 100 100 100

Former 246

(140-432)

197

(148-262)

296

(184-476)

199

(088-452)

Current 721

(484-1075)

520

(422-641)

550

(364-832)

321

(158-651)





1-12 618

(398-958)

365

(282-473)

365

(212-628)

290

(115-727)

13-22 792

(501-1253)

639

(498-820)

541

(323-905)

221

(071-686)

23+ 1112

(660-1870)

853

(635-1150)

901

(504-1610)

637

(210-1930)

P trend lt00001 lt00001 lt00001 00001




of lung cancer





damage





weights



developed world



Obesity

Western diet

Physical inactivity

Smoking







GST enzymes







GSTP1 polymorphism







Smokers














us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang









45-74 years







history from women




51 of the cohort




Heavy smokers (12)


Light smokers (88)





Men (n=27292) Women (n=34028)


Percent 422 214 364 913 25 62


Lung cancer


Never 100

1-12 432 (355-523)

13-22 661 (546-802)

23+ 949 (758-1188)

P for trend lt00001

Smoking status

Lung cancer

RR (95 CI)

Never 100

Former 224 (181-278)

Current 585 (499-687)







Body Mass

Index (kgm2)

Never

smokers

Former

smokers

Current

smokers

Adj HR

(95 CI)

Adj HR

(95 CI)

Adj HR

(95 CI)

lt20 100 100 100

20-lt24 102 (071-146) 092 (057-148) 081 (067-099)

24-lt28 072 (046-110) 101 (059-174) 062 (046-082)

28+ 081 (046-144) 097 (044-212) 050 (028-088)

P for trend 008 089 00001



Smoking

status



Never 100 100 100 100

Former 246

(140-432)

197

(148-262)

296

(184-476)

199

(088-452)

Current 721

(484-1075)

520

(422-641)

550

(364-832)

321

(158-651)





1-12 618

(398-958)

365

(282-473)

365

(212-628)

290

(115-727)

13-22 792

(501-1253)

639

(498-820)

541

(323-905)

221

(071-686)

23+ 1112

(660-1870)

853

(635-1150)

901

(504-1610)

637

(210-1930)

P trend lt00001 lt00001 lt00001 00001




of lung cancer





damage





weights



developed world



Obesity

Western diet

Physical inactivity

Smoking







GST enzymes







GSTP1 polymorphism







Smokers














us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang








Heavy smokers (12)


Light smokers (88)





Men (n=27292) Women (n=34028)


Percent 422 214 364 913 25 62


Lung cancer


Never 100

1-12 432 (355-523)

13-22 661 (546-802)

23+ 949 (758-1188)

P for trend lt00001

Smoking status

Lung cancer

RR (95 CI)

Never 100

Former 224 (181-278)

Current 585 (499-687)







Body Mass

Index (kgm2)

Never

smokers

Former

smokers

Current

smokers

Adj HR

(95 CI)

Adj HR

(95 CI)

Adj HR

(95 CI)

lt20 100 100 100

20-lt24 102 (071-146) 092 (057-148) 081 (067-099)

24-lt28 072 (046-110) 101 (059-174) 062 (046-082)

28+ 081 (046-144) 097 (044-212) 050 (028-088)

P for trend 008 089 00001



Smoking

status



Never 100 100 100 100

Former 246

(140-432)

197

(148-262)

296

(184-476)

199

(088-452)

Current 721

(484-1075)

520

(422-641)

550

(364-832)

321

(158-651)





1-12 618

(398-958)

365

(282-473)

365

(212-628)

290

(115-727)

13-22 792

(501-1253)

639

(498-820)

541

(323-905)

221

(071-686)

23+ 1112

(660-1870)

853

(635-1150)

901

(504-1610)

637

(210-1930)

P trend lt00001 lt00001 lt00001 00001




of lung cancer





damage





weights



developed world



Obesity

Western diet

Physical inactivity

Smoking







GST enzymes







GSTP1 polymorphism







Smokers














us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang








Lung cancer


Never 100

1-12 432 (355-523)

13-22 661 (546-802)

23+ 949 (758-1188)

P for trend lt00001

Smoking status

Lung cancer

RR (95 CI)

Never 100

Former 224 (181-278)

Current 585 (499-687)







Body Mass

Index (kgm2)

Never

smokers

Former

smokers

Current

smokers

Adj HR

(95 CI)

Adj HR

(95 CI)

Adj HR

(95 CI)

lt20 100 100 100

20-lt24 102 (071-146) 092 (057-148) 081 (067-099)

24-lt28 072 (046-110) 101 (059-174) 062 (046-082)

28+ 081 (046-144) 097 (044-212) 050 (028-088)

P for trend 008 089 00001



Smoking

status



Never 100 100 100 100

Former 246

(140-432)

197

(148-262)

296

(184-476)

199

(088-452)

Current 721

(484-1075)

520

(422-641)

550

(364-832)

321

(158-651)





1-12 618

(398-958)

365

(282-473)

365

(212-628)

290

(115-727)

13-22 792

(501-1253)

639

(498-820)

541

(323-905)

221

(071-686)

23+ 1112

(660-1870)

853

(635-1150)

901

(504-1610)

637

(210-1930)

P trend lt00001 lt00001 lt00001 00001




of lung cancer





damage





weights



developed world



Obesity

Western diet

Physical inactivity

Smoking







GST enzymes







GSTP1 polymorphism







Smokers














us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang








Body Mass

Index (kgm2)

Never

smokers

Former

smokers

Current

smokers

Adj HR

(95 CI)

Adj HR

(95 CI)

Adj HR

(95 CI)

lt20 100 100 100

20-lt24 102 (071-146) 092 (057-148) 081 (067-099)

24-lt28 072 (046-110) 101 (059-174) 062 (046-082)

28+ 081 (046-144) 097 (044-212) 050 (028-088)

P for trend 008 089 00001



Smoking

status



Never 100 100 100 100

Former 246

(140-432)

197

(148-262)

296

(184-476)

199

(088-452)

Current 721

(484-1075)

520

(422-641)

550

(364-832)

321

(158-651)





1-12 618

(398-958)

365

(282-473)

365

(212-628)

290

(115-727)

13-22 792

(501-1253)

639

(498-820)

541

(323-905)

221

(071-686)

23+ 1112

(660-1870)

853

(635-1150)

901

(504-1610)

637

(210-1930)

P trend lt00001 lt00001 lt00001 00001




of lung cancer





damage





weights



developed world



Obesity

Western diet

Physical inactivity

Smoking







GST enzymes







GSTP1 polymorphism







Smokers














us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang








Smoking

status



Never 100 100 100 100

Former 246

(140-432)

197

(148-262)

296

(184-476)

199

(088-452)

Current 721

(484-1075)

520

(422-641)

550

(364-832)

321

(158-651)





1-12 618

(398-958)

365

(282-473)

365

(212-628)

290

(115-727)

13-22 792

(501-1253)

639

(498-820)

541

(323-905)

221

(071-686)

23+ 1112

(660-1870)

853

(635-1150)

901

(504-1610)

637

(210-1930)

P trend lt00001 lt00001 lt00001 00001




of lung cancer





damage





weights



developed world



Obesity

Western diet

Physical inactivity

Smoking







GST enzymes







GSTP1 polymorphism







Smokers














us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang










1-12 618

(398-958)

365

(282-473)

365

(212-628)

290

(115-727)

13-22 792

(501-1253)

639

(498-820)

541

(323-905)

221

(071-686)

23+ 1112

(660-1870)

853

(635-1150)

901

(504-1610)

637

(210-1930)

P trend lt00001 lt00001 lt00001 00001




of lung cancer





damage





weights



developed world



Obesity

Western diet

Physical inactivity

Smoking







GST enzymes







GSTP1 polymorphism







Smokers














us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang









of lung cancer





damage





weights



developed world



Obesity

Western diet

Physical inactivity

Smoking







GST enzymes







GSTP1 polymorphism







Smokers














us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang











weights



developed world



Obesity

Western diet

Physical inactivity

Smoking







GST enzymes







GSTP1 polymorphism







Smokers














us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang









Obesity

Western diet

Physical inactivity

Smoking







GST enzymes







GSTP1 polymorphism







Smokers














us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang













GST enzymes







GSTP1 polymorphism







Smokers














us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang









GSTP1 polymorphism







Smokers














us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang











Smokers














us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang















us blood





OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang











OR (95 CI)

Never 100 100 100

Light smoker 116 (087-154) 094 (066-134) 145 (099-213)

Heavy smoker 295 (172-506) 218 (111-429) 412 (215-788)

P for trend 0002 0246 lt00001





Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang









Present 100 100 100

Null 092 (073-116) 083 (062-110) 106 (077-146)



Present 100 100 100

Null 112 (089-141) 123 (093-161) 103 (075-141)



AA 100 100 100

AB 082 (063-106) 086 (063-118) 076 (053-109)

BB 065 (035-121) 074 (035-158) 055 (022-137)

ABBB 080 (062-102) 085 (063-114) 073 (052-104)




No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang







No of ldquonull

or low

activityrdquo GST

genotypes


OR (95 CI) OR (95 CI) OR (95 CI)

0 100 100 100

1 102 (076-136) 098 (068-140) 106 (070-161)

2 095 (069-131) 089 (060-131) 106 (068-165)

3 076 (044-132) 095 (050-178) 048 (019-123)

P for trend 0410 0601 0498










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang










OR (95 CI)

Never 100 100 100

Light smoker 082 (043-155) 035 (015-084) 200 (081-490)

Heavy smoker 134 (038-476) 068 (014-322) 323 (057-181)

P for trend 0916 0087 0085







OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang










OR (95 CI)

Never 100 100 100

Light smoker 109 (070-168) 086 (050-149) 137 (077-244)

Heavy smoker 243 (101-586) 205 (066-633) 301 (105-862)

P for trend 0143 0732 0052







OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang










OR (95 CI)

Never 100 100 100

Light smoker 169 (103-277) 192 (104-354) 139 (071-272)

Heavy smoker 543 (222-132) 425 (136-133) 604 (214-170)

P for trend 00002 0005 0003















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang



















Acknowledgement

Cohort Study Team



Professor Mimi Yu


Dr Renwei Wang







S21 all

Health & Medicine

Transcript of S21 all