Lung Cancer - PowerPoint PPT Presentation

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Lung Cancer

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Title: 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

5
  • 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

6
  • African-Americans have the highest incidence and
    mortality, Hispanics have the lowest

7
  • 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

10
  • Higher incidence and mortality rates are reported
    among men from lower SES groups

11
  • 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

12
  • 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

15
  • 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

16
  • 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

17
  • 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

18
  • Difficult to assess association between alcohol
    and lung cancer due to confounding by smoking
    status
  • Conflicting results of cohort and case-control
    studies

19
  • 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

21
  • 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

22
  • 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

23
  • 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
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