Lung Cancer

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• Most frequently diagnosed cancer worldwide
• About 1.35 million new cases diagnosed worldwide
  each year
• Leading cause of cancer deaths in the United
  States

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• Incidence and mortality rates begin to increase
  between the ages of 45 and 54 and rise
  progressively until age 75
• Median age at diagnosis70.07
• Median age at death71.07

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• Males have a greater lifetime risk of lung cancer
  than females (7.81 vs. 5.8)
• Greater disparity in developing countries where
  cigarette use by females is low

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• African-Americans have the highest incidence and
  mortality, Hispanics have the lowest

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• Patterns of mortality tend to cluster with in
  areas with high prevalence of cigarette smoking
• In the US, highest rates in Kentucky, lowest in
  Utah
• Number of cases highest in California, lowest in
  Alaska
• Worldwide, most cases are seen in the developed
  countries of North America, Western Europe, and
  Australia/New Zealand

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• Current overall 5 year survival rate is 11
• Impacted by age, tumor stage, histological
  subtype, and treatment
• Developed countries have higher survival rates
  than developing countries (13 vs. 9)
• Improvements in diagnostic and therapeutic
  technologies have contributed to an increase in
  survival
• 1 year survival 37 in 1975, 42 in 2000

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• Higher incidence and mortality rates are reported
  among men from lower SES groups

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• Cigarette smoking is the most important risk
  factor for lung cancer
• Causes approximately 90 of male and 75-80 of
  female lung cancer deaths
• By the early 1950s, case control studies in the
  US and Great Britain clearly showed an
  association between smoking and lung cancer
• In 1964, the US Surgeon General released a report
  on the causal relationship

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• United Kingdom
• Cumulative risk of death from lung cancer rose
  from 6 in 1950 to 16 in 1990 in male cigarette
  smokers
• Relative risk of lung cancer after smoking
  cessation begins to decrease after 5 years but
  never reaches the risk of a non-smoker

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• More than 80 carcinogens in cigarette smoke
  according to the International Agency for
  Research on Cancer (IARC)
• Polycyclic aromatic hydrocarbons (PAHs) are a
  well documented lung carcinogen
• NNK has been shown to induce lung carcinoma

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• History of respiratory diseases such as asthma,
  bronchitis, emphysema, hay fever, or pneumonia
  may modify risk
• When combined with smoking, there is a
  complementary cycle of injury and repair that may
  increase risk
• Respiratory diseases may result in chronic immune
  stimulation that causes random pro-oncogenic
  mutations that increase risk
• Relationship is still speculative

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• Animal models have indicated that dietary fat can
  promote chemically induced pulmonary tumors
• Relationship may be confounded by the association
  between smoking status and diet
• Rates of lung cancer are highest in countries
  with greatest fat consumption after controlling
  for smoking

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• Lowered risk associated with consumption of fresh
  vegetables and fruits
• Case-control and cohort studies
• Risk in those with highest intake was about
  one-half of those with lowest intake
• Beneficial micronutrients in fruits and
  vegetables
• Carotenoids
• Isothiocyanates
• Folate
• Selenium

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• Difficult to assess association between alcohol
  and lung cancer due to confounding by smoking
  status
• Conflicting results of cohort and case-control
  studies

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• IARC categorized several occupational agents as
  known carcinogens
• Radon
• Well established lung carcinogen, responsible for
  6.5 of lung cancer deaths in the United Kingdom
  in 1998
• Asbestos
• SMR for lung cancer 1.65, dose dependent risk
• Arsenic
• Bischloromthyl ether
• Chromium
• Nickel
• Polycyclic aromatic compounds
• Vinyl chloride

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• Only a fraction of long-term smokers will develop
  lung cancer
• Likely impacted by genetic susceptibility
• Familial aggregation
• Studies have reported an excess of lung cancer
  mortality in relatives of lung cancer patients

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• Polymorphisms in genes encoding for enzymes
  responsible for detoxification of carcinogens
  affect the internal dose of tobacco carcinogens
  that lung tissue is exposed to
• Many different polymorphisms
• Cytochrome P-450

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• Defective repair of genetic damage is an
  important determinant of susceptibility to lung
  cancer
• Hypersensitivity to carcinogenic exposure
• Many studies have demonstrated that cancer cases
  have a significant decrease in DNA repair
  capacity compared to controls

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• Genes Involved in Methyl Metabolism
• Cell Cycle Control

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• Prevent smoking
• Screening
• Early detection improves resectability and
  survival
• Methods
• Low-dose spiral CT
• Combination of chest X-rays and sputum cytology
• May only be cost-effective in high-risk
  populations

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• Correlating biomarkers from surrogate tissues
  with molecular changes in lung tissue
• Markers should be readily accessible (blood)
• Provide non-invasive evaluation of risk,
  physiologic and pathophysicological states
• Chemoprevention and chemotherapy

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• Cancer Epidemiology, 3rd ed. 2006. Oxford
  University Press
• Centers for Disease Control
• American Cancer Society