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

Background: Only a fraction of cigarette smokers develop lung cancer, sugge sting that people differ in their susceptibility to this disease, We invest igated whether differences in DNA repair capacity (DRC) for repairing tobac co carcinogen-induced DNA damage are associated with differential susceptib ility to lung cancer. Methods: From August 1, 1995, through April 30, 1999, me conducted a hospital-based, case-control study of 316 newly diagnosed l ung cancer patients and 316 cancer-free control subjects matched on age, se x, and smoking status. DRC was measured in cultured lymphocytes with the us e of the host-cell reactivation assay with a reporter gene damaged by a kno wn activated tobacco carcinogen, benzo[a]pyrene diol epoxide, Statistical t ests were two-sided. Results: Overall, lower DRC was observed in case patie nts than in control subjects (P<.001) and was associated with a greater tha n twofold increased risk of lung cancer. Compared with the highest DRC quar tile in the control subjects and after adjustment for age, sex, pack-years of smoking, family history of cancer, and other covariates, reduced DRC was associated with increased risk of lung cancer in a dose-dependent fashion (odds ratio [OR] = 1.8 with 95% confidence interval [CI] = 1.1-3.1, OR = 2. 0 with 95% CI = 1.2-3.4, and OR = 4.3 with 95% CI = 2.6-7.2 for the second, third, and fourth quartiles, respectively; P-trend<.001). Case patients wh o were younger at diagnosis (<60 years old), female, or lighter smokers or who reported a family history of cancer exhibited the lowest DRC and the hi ghest lung cancer risk among their subgroups, suggesting that these subgrou ps may be especially susceptible to lung cancer. Conclusion: The results pr ovide evidence that low DRC is associated with increased risk of lung cance r. The findings from this hospital-based, case-control study should be vali dated in prospective studies.