Tobacco Related Cancers

Philip C. Nasca, MS, PhD, FACE

State University of New York At Albany

School of Public Health

Annual Deaths Attributable to Cigarette Smoking – United States, 200-2004

Assessing Causality A. Strength of Associations: There are mathematical

techniques for measuring how strongly two variables are associated, to be discussed later in the course. Strong associations are more likely to be causal than weak associations; but the fact that an association is weak does not rule out a causal association

B. Consistency: Repeated observation of an association in different populations, at different times, using different methodologies

C. Biologic Credibility (Plausibility):An assessment of how credible the inference is, based on available biologic evidence

Assessing Causality D. Temporality (Time Sequence): The necessity that cause

precede effect in time. This is a necessary part of causal inference, but sometimes temporal information is not available.

E. Biologic Gradient (Dose-Response Relationship): The observation of a gradient of risk associated with the degree of exposure.

F. Experimental Evidence: Strong, but such information is seldom available for human populations. Animal data are often used, e.g. to test if a particular substance may be carcinogenic and then these data are used by analogy, to support observational data that the substance is associated with cancer in humans.

Assessing Causality G. Coherence: Agreement between the hypothesized cause

and the known facts of the natural history and biology of the disease. Very similar to “biologic credibility”.

H. Analogy: A very weak criterion since an analogy with a different causal association may not pertain to the association in question. Good for hypothesis generation.

I. Specificity: Of historic and pedagogic interest only. This criterion states that one cause should lead to a dingle, not multiple effects. This has been advanced by many others (Koch-Henle postulates of infectious disease), but, even with reservations, it appears obvious that single events/causes/exposures can have many effects.

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Relative Risk

Amount Smoked - Grams Tobacco/Day

Risks For Cancers of The Upper Digestive and Respiratory Tracts in Male Smokers Relative to That of Nonsmokers Who Drink Little of No AlcoholExample – Cancer of the Larynx Wynder et al. (1976)

Risks For Cancer of the Pancreas in Cigarette Smokers Relative to That For Nonsmokers – Wynder et al. (1983)

0

0.5

1

1.5

2

2.5

3

Relative Risk

0 1 to 10 11 to 20 21 to 30 >/=31Daily # Cigarettes

MalesFemales

Risk for Cancer of the Hypolarynx/Epilarynx According to Daily Consumption of Tobacco and Alcohol – Tuyns et al (1988).

0

20

40

60

80

100

120

140

Relative Risk

0 to 7 8 to 15 16 to 25 26+# Cigarettes/Day

0-4041-8081-120>/=121

Alcohol Consumption(g Ethanol/day)

*Risk Relative To Those Who Consume 0-40g ethanol/day and 0-7 g tobacco/day

Table 15. Risks for cancer of the bladder of male cigarette smokers relative to those for nonsmokers - Examples

Country Daily No. of Cigarettes

Relative Risk*

Reference

USA Nonsmokers 1.0 Wynder&Goldsmith (1977)

1-10 1.411-20 2.4

21-30 2.7

31-40 2.3

>/=41 3.3

CANADA Nonsmokers 1.0 Howe et al. (1980)<10 2.610-20 3.8>20 5.1

*Ratio between the occurrence rate of cancer among smokers and that among nonsmokers

Figure 7-7. Table of concentrations of selected compounds in nonfilter cigarette mainstream smoke (MS) and the ratio of their relative distribution in sidestream smoke (SS):MS* - Examples

MS SS:MS

Vapour Phase

Carbon Monoxide 10-23 mg 2.5-4.7

Benzene 12-48 ug 10

Formaldehyde 70-100 ug 8-15

Particulate Phase

Nicotine 1.7-3.3 1.8-3.3

2-Naphthylamine 1.7ng 30

Benzopyrene 20-40 2.5-3.5

Range of Average Indoor Concentrations of Noteable ETS Contaminants Associated With Smoking Occupancy

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10111213141516

Cotinine (mg/ml)

Mean Cotinine(mg/ml)

Number of Exposures in the Past 4 Days

Figure 3-16. Urinary cotinine concentrations by number of reported exposures to tobacco smoke in the past 4 days among 663 nonsmokers, Buffalo, New York, 1986

Table 5-11. Exposure Response Trends For Females – Smoking By Spouse

Study Exposure RR* C.I

Font (Years) 0 1.01-15 1.33 (0.93, 1.89)16-30 1.40 (0.96,2.05)>30 1.43 (0.99, 2.09)

Font (Pack Years) 1.00<15 1.03 (0.73, 1.46)15-39 1.26 (0.85, 1.87)40-79 1.49 (0.98, 2.27)>/=80 1.70 (0.82, 3.49)

Table 5-11. Exposure Response Trends For Females – Smoking By Spouse

Study Exposure RR* C.I

Geng (Cig./Day) 0 1.01-9 1.40 (1.1, 1.8)10-19 1.97 (1.4, 2.7)>/= 20 2.76 (1.9, 4.1)

Geng (Years) 0 1.0<20 1.49 (1.15, 1.94)20-39 2.23 (1.54, 3.22)>/=40 3.32 (2.11, 5.22)

HISTORY OF SMOKELESS TOBACCO

Smokeless tobacco was used in the United States in the early 1600s when snuff made its way to the Jamestown Colony in Virginia through the efforts of John Rolfe in 1611 (1). Evidence of tobacco chewing, however, was not until a century later in 1704 (2).

A Chinese Law in 1683 Threatened That Anyone Possessing Tobacco Would Be Beheaded

HISTORY OF SMOKELESS TOBACCO

In the past, tobacco use was considered by some as beneficial.•3500 B.C. tobacco an article of value – Mexico and Peru•Alleviation of hunger pains•Medicinal Uses: In Native Americans – to alleviate toothaches, disinfect cuts and relieve the effects of snake, spider, and insect bites•19th and 20th centuries used to relieve toothache, to cure neuroglia, bleeding of gums, and scurvy•To preserve and whiten teeth and prevent decay

CHEWING TOBACCO•Looseleaf•Plug•Twist

SNUFF•Moist•Dry

Does smokeless tobacco cause cancer?Smokeless tobacco is tobacco that is not burned. It includes chewing tobacco, dip, snuff, and betel quid*.

At least 28 chemicals in these products have been found to cause cancer, including:

• Esophageal cancer• Mouth cancer• Pancreatic cancer• Esophageal cancer• Lip cancer• Mouth cancer• Pharynx cancer• Tongue cancer

*Betel quid is a combination of betel leaf, areca nut, and slaked lime. In many countries, tobacco is added, and the product is known as gutka, ghutka, or gutkha. Like other smokeless tobacco products, betel quid and gutka are known to cause various cancers

Number of Studies Evaluated

Cancer Site Case-Control Cohort Average Relative Risk Lung >100 37 15.0-30.0 Urinary tract 50 24 3.0 Upper aero-digestive tract: Oral Cavity

16

3

4.0-5.0

Oro-and hypopharynx 12 3 4.0-5.0 Oesophagus (SCC or NOS) 35 19 2.0-5.0 Larynx 25 5 10.0 Esophagus (adenocarcinoma) 10 NA 1.5-2.5 Pancreas 38 27 2.0–4.0 Nasal cavity, paranasal sinuses 9 1 1.5-2.5 Nasopharynx 19 2 1.5-2.5 Stomach 44 27 1.5-2.0 Liver 29 29 1.5-2.5 Kidney 13 8 1.5-2.5 Uterine cervix 49 14 1.5-2.5 Myeloid leukemia Not reviewed 12 1.5-2.0

Table 9-3 Cancer sites for which there is “sufficient” evidence of carcinogenicity of tobacco smoking according to the International Agency for Research on cancer

70

520

70

340

500

220

190

0

100

200

300

400

500

1950 2000 2025 2050

Year

Toba

cco

deat

hs (m

illio

n)

Baseline

If proportion of yound adultstaking up smoking halves by2020If adult consumption halvesby 2020

Figure 9-12. Unless current smokers quit, tobacco deaths will rise dramatically in the next 50 years

IMPACT OF TOBACCO ON GLOBAL HEALTH