Repair of tobacco carcinogen-induced DNA adducts and lung cancer risk: A molecular epidemiologic study

Abstract

Background: Only a fraction of cigarette smokers develop lung cancer, suggesting that people differ in their susceptibility to this disease. We investigated whether differences in DNA repair capacity (DRC) for repairing tobacco carcinogen-induced DNA damage are associated with differential susceptibility to lung cancer. Methods: From August 1, 1995, through April 30, 1999, we conducted a hospital-based, case-control study of 316 newly diagnosed lung cancer patients and 316 cancer-free control subjects matched on age, sex, and smoking status. DRC was measured in cultured lymphocytes with the use of the host-cell reactivation assay with a reporter gene damaged by a known activated tobacco carcinogen, benzo[a]pyrene diol epoxide. Statistical tests were two-sided. Results: Overall, lower DRC was observed in case patients than in control subjects (P <60 years old), female, or lighter smokers or who reported a family history of cancer exhibited the lowest DRC and the highest lung cancer risk among their subgroups, suggesting that these subgroups may be especially susceptible to lung cancer. Conclusion: The results provide evidence that low DRC is associated with increased risk of lung cancer. The findings from this hospital-based, case-control study should be validated in prospective studies.