BENZO[A]PYRENE DIOL EPOXIDE-INDUCED 3P21.3 ABERRATIONS AND GENETIC PREDISPOSITION TO LUNG-CANCER

3p deletion, a common chromosome defect in lung cancer, occurs more fr equently in the Lung tumor tissues of smoking patients than it does in those of nonsmoking patients. This pilot study evaluated whether 3p a berrations induced by benzo[a]pyrene diol epoxide (BPDE), the metaboli c product of benzo[a]pyrene, a constituent of tobacco smoke, were more common in the peripheral blood lymphocytes of 40 lung cancer patients than they were in those of 54 matched controls. Our hypothesis was th at 3p sensitivity to BPDE reflects the susceptibility of a specific lo cus to damage from carcinogens in tobacco smoke. BPDE-induced chromoso me 3p21.3 aberrations were significantly more frequent in cases (34.1 per 1000) than they were in controls (22.1 per 1000; P < 0.0001), Howe ver, no such difference was observed for 6q27, a control locus. Using the median value in the controls (20 per 1000) as a cutoff point to cl assify BPDE-induced sensitivity at 3p21.3 and after adjustment by age, sex, ethnicity, and smoking status, 3p BPDE sensitivity was associate d with an elevated risk of 14.1 (95% confidence interval: 3.5, 56.2) f or lung cancer, There was also a dose-response relationship between th e degree of BPDE sensitivity at 3p21.3 and increased risk for lung can cer. Therefore, 3p may be a molecular target for BPDE damage in lung c ancer cases.