Lung cancer: genetics of risk and advances in chemoprevention

The current article reviews recent advances in genetic susceptibility and chemoprevention of lung cancer.

Linkage analysis has identified a locus on chromosome 6q23-25 that determines susceptibility to lung cancer in families with multiple members with cancer of the lung, throat, and larynx. Obligate gene carriers are sensitive to even small tobacco smoke exposure in terms of increased lung cancer risk. Variation in other genes, particularly those regulating the activation or inactivation of carcinogens, has been implicated in determining lung cancer risk. Epidemiologic and preclinical studies suggest that chemoprevention of lung cancer is an achievable goal. Early trials with beta-carotene supplementation, however, have revealed a harmful effect. Promising new agents must be evaluated in both preclinical models and in intermediate end point biomarker trials before being taken to large primary prevention trials, and lung cancer chemoprevention should only be attempted within controlled clinical trials.

We are poised to learn a great deal about the genetic susceptibility to lung cancer, which will not only allow definition of groups with extremely high risk, but may also yield new insights into processes that determine innate susceptibility or resistance to lung carcinogenesis. Chemoprevention of lung cancer is not yet ready for clinical application. As a result of the large number of lung cancer deaths and the large number of at-risk individuals, even modestly effective chemoprevention could save many lives.