Lung Cancer Causes

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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 Generals 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 274430-2

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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 Males
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Years after Quitting Smoking and Relative Risks
of Lung Cancer - Males
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Risk Reduction

• Abstinence gt 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
  199276305-31.

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Lung Cancer Risk Reduction after Smoking
Cessation. Ebbert et. al. J Clin Oncol
21921-926, 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 exposuregt25 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 AmphibolegtChrysotile 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
  12350-358, 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 (lt40) 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
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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 226756-761, 2003
• Await Natl Lung Cancer Screening Trial to
  evaluate disease-specific mortality benefit of CT
  screening.

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