lung cancer molecular pathology of cancer boot camp january 4, 2012 jennifer rider, scd
TRANSCRIPT
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Lung CancerMolecular Pathology of Cancer Boot CampJanuary 4, 2012Jennifer Rider, ScD
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Learning objectives
•Basic descriptive epidemiology•Major risk factors•Historical perspective on establishing
smoking as a causal agent •Key differences in disease among smokers
and non-smokers
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Five-year survival rates
ACS Cancer Facts & Figures 2011
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Lung Cancer Epidemiology: Risk factors1. Cigarette smoking 2. Environmental tobacco smoke3. Radon4. Occupational exposures
a. Asbestos b. Asbestos x smoking interactionc. Cooking oil vapors and indoor coal burning
5. Ambient air pollution6. Genetic factors
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Smoking▫Lung cancer risk depends on:
▫Years smoked▫Age smoking initiated▫Number of cigarettes smoked per day▫Tar/Nicotine
▫Risk roughly proportional to yield (down to one-half risk)
▫BUT negated by compensation in numbers smoked
▫Risk elevated in cigar/pipe smokers▫Amount smoked and inhaling contribute
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Constituents of the cigarette
•7000 chemicals▫Carbon monoxide/vapor phase components▫Nicotine▫“Tar” = particulate – (nicotine + water)▫60 carcinogens▫Additives
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Selected carcinogens in cigarette smoke•Policyclic aromatic hydrocarbons (PAH):
benzo[a]pyrene•Tobacco-specific nitrosamines (TSNA)•Aromatic amines: 4-aminobiphenyl•Benzene•Arsenic, Nickel, Chromium•Polonium-210
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Smoking Cessation• Among individuals who have smoked less
than 20 years• Lung cancer risk reverts to non-smoker level
after about 15 years of cessation.• Among individuals who have already
developed lung cancer• Quitting reduces risks of developing a second
cancer
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Lung cancer incidence and trends, and smoking behavior among men – United States
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Tobacco Use in the US, 1900-1999
0
500
1000
1500
2000
2500
3000
3500
4000
4500
5000
Year
Per
Cap
ita C
igar
ette
Con
sum
ptio
n
0
10
20
30
40
50
60
70
80
90
100
Age
-Adj
uste
d Lu
ng C
ance
r D
eath
R
ates
*
*Age-adjusted to 2000 US standard population.
Source: Death rates: US Mortality Public Use Tapes, 1960-1999, US Mortality Volumes, 1930-1959, National Center for Health Statistics, Centers for Disease Control and Prevention, 2001. Cigarette consumption: Us Department of Agriculture, 1900-1999.
Per capita cigarette consumption
Male lung cancer death rate
Female lung cancer death rate
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0%5%
10%15%20%25%30%35%40%45%
% s
mo
kers
Current smoking prevalence in US, 1965-1998
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Smoking prevalence by sex
0%
10%
20%
30%
40%
50%
60%
70%
World East Asia/Pacific
U.S.
Men
Women
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1933: JAMA begins to accept advertising for cigarettes
“Just as pure as the water you drink…and practically untouched by human hands.”
--Chesterfield advertisement, NY State
Journal of Medicine, 1933
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“The following hints may prove helpful. In combination they are nearly perfect and 99 44/100% of the nicotine will go into the filter or your friends’ faces.” Consumer Reports, 1938
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Barriers to acceptance of smoking-lung cancer relationship•Ecologic data - other plausible
alternatives•Smoking common in scientific community•Influence of tobacco companies•Novelty of epidemiological techniques•Strength of infectious disease model
▫Necessary and sufficient causes▫Isolate and identify agent▫Laboratory/animal evidence key▫Smoking associated with multiple diseases
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A new model of causality
•Bradford Hill’s guidelines▫Strength of association▫Consistency▫Specificity▫Temporal sequence▫Dose-response/biologic gradient▫Biological plausibility▫Coherence▫Experimental evidence▫Analogy
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•Active smoking accounts for 90% of lung cancer deaths, but only 10% smokers develop lung cancer
SmokingGenetic
Polymorphisms
Lung cancer risk
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Lung Cancer Subtypes
•Squamous cell carcinoma•Adenocarcinoma•Large-cell carcinoma•Small-cell undifferentiated carcinoma
>90% of Lung
Cancers in US
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Primarily adenocarcinoma
Primarily SCLC and squamous cell carcinoma
Sun et al., Nature Reviews Cancer 2007
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Lung Cancer in Never Smokers
•Estimated 25% of lung cancers not attributable to smoking▫15% among men▫53% among women
•7th leading cause of cancer death worldwide
•Only relatively weak risk factors identified•Distinct histological, geographical and
gender distribution
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Sun et al., Nature Reviews Cancer 2007
Proportion of Lung Cancer in Never Smokers
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Sun et al., Nature Reviews Cancer 2007
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Mutation profile among smokers vs. nonsmokers
Sun et al., Nature Reviews Cancer 2007
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Gefitinib (Iressa) effectiveness among Asian patients with NSCLC
Lim et al., Br J Cancer 2005
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