BENZO[A]PYRENE DIOL EPOXIDE AND BLEOMYCIN SENSITIVITY AND SUSCEPTIBILITY TO CANCER OF UPPER AERODIGESTIVE TRACT

Background: Tobacco smoking is an established risk factor for cancers of the upper aerodigestive tract, and measurement of chromosomal aberr ations, i.e., chromatid breaks, induced in lymphocytes in vitro by ble omycin has been shown to be a predictor of risk for these cancers. In a case-control study, we recruited case subjects who were previously t reated with surgery and/or radiotherapy for stage I or stage II squamo us cell carcinoma of the head and neck to test the hypothesis that lym phocytic chromatid breaks induced by benzo[a]pyrene diol epoxide (BPDE ), a tobacco mutagen, may also be associated with risk of developing c ancers of the upper aerodigestive tract, Methods: Case subjects were m atched to control subjects on the basis of age, sex, ethnicity, and sm oking status. Primary lymphocytes from 67 case subjects and 81 control subjects were treated with 2 mu M BPDE for 24 hours, and the frequenc y of induced chromatid breaks was determined. All statistical tests we re two-sided. Results: Lymphocytes from case subjects compared with ly mphocytes from control subjects showed significantly more breaks per c ell induced by BPDE (mean +/- standard deviation, 0.77 +/- 0.38 versus 0.49 +/- 0.25; P<.001), Lymphocytes from 64.2% of case subjects were sensitive to BPDE (using a cutoff value of greater than or equal to 0. 60 break per cell), Subjects in the highest quartile of chromatid brea ks had an approximately 20-fold increased risk of cancer compared with those in the lowest quartile after adjustment for age, sex, ethnicity , and smoking status, The association between BPDE sensitivity and can cer risk was higher in former smokers than in current smokers and high er in younger patients than in older patients. Subjects with sensitivi ty to both BPDE and bleomycin were at a 19.2-fold increased risk of ca ncer compared with those who were not sensitive to either agent. Concl usions: Mutagen sensitivity assays may aid in identifying individuals at risk of cancer, and use of parallel assays with two mutagens may im prove risk predictability.