Molecular epidemiology to better predict lung cancer risk.

Although it is clear that smoking causes lung cancer, it is not known why some smokers develop the disease while others do not. Little is also known regarding risk factors for lung cancer among never-smokers, particularly women, or why women with lung cancer are more likely to have a family history of cancer, to be diagnosed at a young age, or to have adenocarcinoma. The application of molecular epidemiology to the study of lung cancer risk might facilitate elucidation of these questions. In this review, the molecular epidemiology of lung cancer is discussed, with an emphasis on studies of genetic variability in metabolic pathways as a means for determining susceptibility. Work that has assessed intermediate markers of risk, such as DNA adducts, is also presented, as are studies of tumor tissue alterations, such as mutations and DNA methylation, in relation to risk of lung cancer. Finally, approaches to evaluating factors that might explain the differing epidemiology of lung cancer between men and women are also presented. It is likely that, by incorporating biomarkers of susceptibility, exposure, and effect, molecular epidemiologic approaches might better define factors that explain some of the variability in lung cancer risk.