lung cancer causes carcinogens, such as cigarettes radiation genetic susceptibility viruses...
TRANSCRIPT
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Lung Cancer Causes
• Carcinogens, such as cigarettes
• Radiation
• Genetic susceptibility
• Viruses
Wikipedia.org
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Epidemiology of Lung Cancer
And what to do about it
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STOP SMOKING!
Only 2% of Lung Cancer patients are lifelong nonsmokers
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Lung Cancer
• Most common cause of cancer death• 154,900 deaths in 2002• 127,000 combined colorectal, breast and
prostate deaths• Smoking/Lung Cancer first linked in 1950-
Doll and Hill• Surgeon General’s 1964 statement
-“cigarette smoking is the major cause of lung cancer…”
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Tobacco – Cancer Linked Directly
A specific metabolite of benzo(a)pyrene, a constituent of tobacco smoke, damages three
specific loci on the p53 tumor-suppressor gene that are known to be abnormal in 60%
of primary lung cancer.
Denissenko et. al. Science 1996 274:430-2
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Magnitude of Risk
• Total lifetime consumption
• Number of cigarettes• Duration of smoking• Age at onset• Degree of inhalation• Tar and Nicotine
content• Use of filter
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Number of Cigarettes Smoked and Relative Risks of Death from
Lung Cancer among MalesNo. per Day US Veterans British Doctors
None 1.0 1.0
Current smokers 12.1 14.0
1-9 5.5 7.8
10-19 9.9 17.4
20-39 17.4 25.1
>40 23.9 --
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Years after Quitting Smoking and Relative Risks of Lung Cancer -
MalesYears after Cessation
US Veterans British Doctors
0 11.3 15.8
1-4 18.8 16.0
5-9 7.5 5.9
10-14 5.0 5.3
15-19 5.0
>20 2.1 2.0
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Risk Reduction
• Abstinence > 15 years has an 80-90% reduction in risk compared with current smokers
• Lung CA risk always higher in former smokers than never smokers. Former smokers have 10-80% greater risk than nonsmokers
Newcombe and Carbone. Med Clin North Am 1992;76:305-31.
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Lung Cancer Risk Reduction after Smoking Cessation. Ebbert et. al. J Clin Oncol 21:921-926,
2003
• 37,078 females
• Elevated risk even thirty years later
• Persisting risk of adenocarcinoma among former smokers
• Former light smokers still had a greater than 2-fold increased risk up to 30 years after smoking abstinence
• Although risk of cancer does not return to baseline for decades, significant decrease in first 10 years of abstinence
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Other Risks – Smoking
• Cigar and Pipe Smoking –They DO inhale
• Environmental Smoke – Passive or Second-Hand – Yes, weaker links, but dose-response shown
• Marijuana and Cocaine Smoking
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Environmental Tobacco Smoke
• Duration longer. Dose-response
• Household exposure>25 smoker yrs. doubled risk
• Spousal tobacco use asso. with 30% incr. risk(80 pk yr asso. with 80% incr.)
• Risk increased 24% if lived with smoker
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Genetic Influences
• Glutathione S-transferase M1 detoxifies carcinogens in tobacco smoke
• More polymorphisms noted among women with lung cancer exposed to ETS compared with those not exposed, suggesting these mutations promote tumorigenesis
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Occupational and Environmental Carcinogens
• Asbestos – Amphibole>Chrysotile fibers• Radon – gaseous decay of U-238, Ra-226
(summary risk 1.14)• Arsenic,bis-chloromethyl ether, chromium,
formaldehyde, ionizing radiation, nickel, polycyclic aromatic hydrocarbons, hard metal dust, vinyl chloride
• Air pollution
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Other Risk Factors
• Familial-1st degree have 1.5-3 fold risk• Dietary Factors- low antioxidents, esp A
and E. Beta-carotene conflicting data• Preexisting Benign Lung Disease – IPF,
Asbestosis, COPD• Oncogenic Viruses not proven –
BAC/Jaagsiekte and Squamous/Human Papilloma Virus
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Dietary Factors
• CARET Trial-Heavy smokers who consumed more fruit and vegetables reduced their risk of cancer, but supplementation with Beta-carotene negated the effects of increased plant foods
Neuhouser et al Cancer Epidemiol Biomarkers Prev 12:350-358, 2003
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Gender Differences – Death Rate
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Gender Smoking Trends
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Endocrine Factors & Lung CA
• Early age at menopause (<40) associated with reduced risk of AdenoCA lung
• Estrogen RT associated with higher risk AdenoCA lung
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Gender Histology Differences
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Histology Distribution for Three Time Intervals
Period Squamous Adeno Small cell Large cell
1973-77 13.4 10.5 5.9 --
1978-82 15.1 14.2 8.2 3.9
1983-1987
15.3 16.7 9.4 4.9
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Lung Cancer Screening - CT
• Nodules found, but with op mort 3.8% for pulm wedge resection in community hosp., the mortality benefit of CT screening for unselected patients not yet clear. Eight/39 were surgeries for benign disease
Swensen et al Radiology 226:756-761, 2003
Await Nat’l Lung Cancer Screening Trial to evaluate disease-specific mortality benefit of CT screening.
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