Genetic susceptibility appears to modulate an individual's risk of tobacco-induced
carcinoma. One
biomarker of such susceptibility, chromatid 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 evaluate the association between the
BPDE-induced chromatid breaks per cell (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 obtained from 60 SCCHN patients and 112 healthy controls matched for age, sex, ethnicity, and smoking status. After incubation and exposure to
BPDE, metaphase spread slides were created, and the average b/c values were 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 analysis using logistic regression models and including age, sex, ethnicity, and smoking status,
BPDE-induced b/c values remained an independent risk factor for disease (P < 0.05, adjusted OR=2.36, 95% CI=1.17-4.79). Furthermore, when b/c values were divided based on control values into low, medium, and high tertiles, there was a dose-response relationship: 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
carcinogenesis.