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, 3rd ed. 2006. 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.