MUTAGEN SENSITIVITY TO BENZO(ALPHA)PYRENE DIOL EPOXIDE AND THE RISK OF SQUAMOUS-CELL CARCINOMA OF THE HEAD AND NECK

Genetic susceptibility appears to modulate an individual's risk of tob acco-induced carcinoma. One biomarker of such susceptibility, chromati d breaks induced in vitro in lymphocytes by the mutagen bleomycin, is an independent risk factor for several malignancies. To date, the more etiologically appropriate mutagen benzo(a)pyrene diol epoxide (BPDE) has only been used in one lung cancer study, Our objective was to eval uate the association between the BPDE-induced chromatid breaks per cel l (b/c) values and the risk of squamous cell carcinoma of the head and neck (SCCHN) in a pilot case-control study. Blood samples were obtain ed from 60 SCCHN patients and 112 healthy controls matched for age, se x, ethnicity, and smoking status, After incubation and exposure to BPD E, metaphase spread slides were created, and the average b/c values we re determined, Univariate analysis identified elevated BPDE-induced b/ c values as a significant risk factor [P < 0.05, crude odds ratio (OR) = 1.94, 95% confidence interval (CI) = 1.00-3.74]. On multivariate an alysis using logistic regression models and including age, sex, ethnic ity, and smoking status, BPDE-induced b/c values remained an independe nt risk factor fbr disease (P < 0.05, adjusted OR = 2.36, 95% CI = 1.1 7-4.79), Furthermore, when b/c values were divided based on control va lues into low, medium, and high tertiles. there was a dose-response re lationship: an adjusted OR of 1.28 (95% CI = 0.49-3.33) for the middle tertile and an adjusted OR of 4.09 (95% CI = 1.67-10.0) for the high tertile (trend test, P < 0.001). These findings suggest that high BPDE -induced b/c values in lymphocytes are an independent risk factor for SCCHN and a marker for genetic susceptibility to tobacco-induced carci nogenesis.