Lung cancer: genetics of risk and advances in chemoprevention.
OBJECTIVE
The current article reviews recent advances in genetic susceptibility and chemoprevention of lung cancer.


RESULTS
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.


CONCLUSIONS
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.
Keith
Robert L
RL
Pulmonary Sciences and Critical Care Medicine Division, Denver Veterans Affairs Medical Center, University of Colorado Cancer Center, University of Colorado at Denver and Health Sciences Center, Colorado 80220, USA.
Miller
York E
YE
D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000517:prevention & control*
D016588:Anticarcinogenic Agents