Kidney Cancer Overview - Incidence, Causes and Risk Factors

8/6/2019 Kidney Cancer Overview - Incidence, Causes and Risk Factors

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May 2010 KCA Patient - Survivor Seminar

Kidney Cancer Overview -

Incidence, Causes and RiskFactors

Dr. Paul Nathan

Mount Vernon Cancer CentreUK


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Cells

Were made up of them

Originate from pluripotent stem cells

(able to turn into any type) & thendifferentiate

Normally proliferation, differentiation,

invasion tightly controlled


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Under normal circumstances.

Cell cycle tightly controlled

Fidelity of DNA replication v. high

Errors undergo programmed cell death(apoptosis)


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Cancer cells.

Lose proliferation control

Lose balance between proliferation &

apoptosis

Invade

Stimulate angiogenesis (new bloodvessel formation)


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All cancer cells within acancer are not exactly the

same Mutations in quality control machinery

allows genetic errors to accumulate Mutations in cell death control allows

cells to survive even when damaged

Cancer populations thereforeheterogeneous


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Implications of Heterogeneity

Likely that some cells survive post treatment

Underpins rationale for combination treatment Underpins rationale for anti-angiogenic

treatment

However in most cancers, despite

combination treatment, some cells survive In which case it may be better to use therapies

sequentially


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Cancer and Darwin

Cancer cells equipped for natural selection

Intrinsically highly genetically unstable

Infinitely variable Survive despite huge selection pressures

Which is why metastatic disease is so difficultto treat.


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DeathsMalesFemalesPersons

Crude rate per 100,000 populationMalesFemalesPersonsAge-standardised rate (European) per 100,000 populationMales

CI 95% 5.9 6.4 4.8 7.0 5.4 7.2 4.3 7.5 5.9 6.4

FemalesCI 95% 2.6 2.9 2.5 3.9 3.4 4.6 2.1 4.2 2.8 3.1

PersonsCI 95% 4.1 4.5 3.8 5.1 4.5 5.5 3.4 5.2 4.2 4.5

Table 2.1: Number of deaths and mortality rates of kidney

cancer, UK, 2005England Wales Scotland N.Ireland UK

2,2041,094 80 168 34 1,3761,849 111 193 51

3,580

7.5 7.7 7.9 6.1 7.5

2,943 191 361 85

4.55.9 6.4 7.1 5.0 6.04.3 5.2 6.4 3.9

6.1

2.8 3.2 4.0 3.1 2.9

6.2 5.9 6.3 5.9

4.44.3 4.4 5.0 4.3


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The 20 most common causes of death from cancer, UK, 2008


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0

100

200

300

400

500

600

700

0-4

5-9

10-14

15-19

20-24

25-29

30-34

35-39

40-44

45-49

50-54

55-59

60-64

65-69

70-74

75-79

80-84

85+

Age at diagnosis

0

20

40

60

80

Rateper100,0

00populatio

n

Male cases Female cases

Male rates Female rates

Figure 1.2: Numbers of new cases and age specific incidence rates,

by sex, kidney cancer, UK 2004


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0

5

10

15

1993

1994

1995

1996

1997

1998

1999

2000

2001

2002

2003

2004

Year of diagnosis

males females persons

Figure 1.8: Age standardised (European) incidence rates, kidney cancer, bysex, UK, 1993-2004


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0 5 10 15 20 25

India

Indonesia

Egypt

China

Ethiopia

Brazil

Japan

United Kingdom

Denmark

Australia

Canada

France

USA

EstoniaCzech Republic

Rate per 100,000 population

Males

Females

Figure 1.3: World age-standardised incidence rates for kidney cancer, selected countries,

2002 estimates


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Causes of Renal Cell

Carcinoma Age, Sex Obesity

Accounts for 25% of cases

Smoking Accounts for 10-15% of female and 20-30% of

male cases

Hypertension

Renal cystic disease. Dialysis

Family history - siblings / children?

Familial


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Sub-types of RCC

Clear cell (conventional) 70-75%

Papillary 10-15%

Type 1 Type 2

Chromophobe < 5%

Collecting Duct


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Inherited Forms of RCC


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HIF regulatedgenes

Semenza, Nature Reviews Cancer 3 (10) 2003


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Siemann group, Eur J Cancer


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Summary

Cancer cell evolution cant fight successful

surgery - early diagnosis

Modifiable risk factors - smoking & obesity Improved understanding of underlying genetic

lesions will allow

Optimal use of available drugs

Discovery of new advances


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Familial vs Sporadic Cancers

2 copies (allelles) of every gene

Generally need both copies mutated to

have major effect upon function Inherited cancers - mutated allelle passedon to next generation Only need a single acquired mutation

Familial cancers therefore in younger adults

Kidney Cancer Overview - Incidence, Causes and Risk Factors

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