Genetic Susceptibility and Risk Factors Associated with Familial Lung Cancer

Familial lung cancer is the lung cancer that recurs in families due to some genetic predisposition. Although environmental factors play the main role in causing lung cancer but genetic susceptibility to lung cancer has also been confirmed. The work on familial lung cancer started 46 years before and is still going on. Various case control and cohort studies of the relationship between family history and risk of lung cancer have provided some evidence of familial aggregation of lung cancer. Genetic modeling studies have also suggested that familial aggregation of lung cancer may be due to inheritance of only a few genetic factors and established evidence for inheritance of a rare major autosomal gene that acts in conjunction with cigarette smoking to produce an earlier age at onset of the cancer. A major susceptibility locus influencing lung cancer risk has been localized to 6q23–25 by genome wide linkage analysis. This locus was further refined to identify a single candidate gene and it was concluded that RGS17 is a major candidate for the familial lung cancer susceptibility locus on chromosome 6q23-25. Some linkage has been found between familial lung cancer and some loci on chromosome 12 and 15. Susceptibility to lung cancer is also affected by polymorphism shown by some DNA repair genes and in genes coding for enzymes that metabolize tobacco carcinogens. Accepting and understanding risk associated with family history of lung cancer is essential in the clinical setting. The lung cancer community would benefit from a risk prediction model based on age, race, sex, family history, smoking history, and pulmonary function. Family history should be tested as another marker of “high risk” for lung cancer in spiral CT screening studies and chemoprevention trials.