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

 Incidence and mortality rates begin to increase between the ages of 45 and 54 and rise progressively until age 75  Median age at diagnosis=70.07  Median age at death=71.07

 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

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

 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

 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

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

 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

 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

 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

 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

 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

 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

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

 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

 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

 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

 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

 Genes Involved in Methyl Metabolism  Cell Cycle Control

 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

 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

 Cancer Epidemiology, 3 rd ed Oxford University Press  Centers for Disease Control  American Cancer Society

 Why do you think lung cancer is the most frequently diagnosed cancer worldwide?  What is the reason for geographic variation in the rates of lung cancer?  Describe factors contributing to lung cancer development, other than smoking.  If somebody quits smoking, does the risk of cancer development return to the level of non-smoker? Describe the pattern.