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Benzo[a]pyrene Diol Epoxide-induced 3p21.3 Aberrations and Genetic Predisposition to Lung Cancer¹

Departments of Epidemiology [X. W., Y. Z., S. E. H., M. R. S.] and Thoracic and Head and Neck Medical Oncology [W. K. H.], The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030; School of Public Health [X. W., Y. Z.], The University of Texas Health Science Center at Houston, Houston, Texas 77030; and Department of Pediatrics and Hannon Center for Therapeutic Oncology [G. E. T., J. D. M.], The University of Texas Southwestern Medical Center, Dallas, Texas 75235

3p deletion, a common chromosome defect in lung cancer, occurs more frequently in the lung tumor tissues of smoking patients than it does in those of nonsmoking patients. This pilot study evaluated whether 3p aberrations induced by benzo[a]pyrene diol epoxide (BPDE), the metabolic 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 that 3p sensitivity to BPDE reflects the susceptibility of a specific locus to damage from carcinogens in tobacco smoke. BPDE-induced chromosome 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). However, 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 classify BPDE-induced sensitivity at 3p21.3 and after adjustment by age, sex, ethnicity, and smoking status, 3p BPDE sensitivity was associated with an elevated risk of 14.1 (95% confidence interval: 3.5, 56.2) for lung cancer. There was also a dose-response relationship between the degree of BPDE sensitivity at 3p21.3 and increased risk for lung cancer. Therefore, 3p may be a molecular target for BPDE damage in lung cancer cases.

¹ This work was supported by National Cancer Institute Grants 1RO3 70191, CA 55769, CA 68437, and SPORE P50 CA 70907.

² To whom requests for reprints should be addressed, at Department of Epidemiology, Box 189, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030.

Received 12/ 4/97. Accepted 3/ 2/98.

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