Mutagen sensitivity to benzo(a)pyrene diol epoxide and the risk of squamous cell carcinoma of the head and neck.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Wang, LE; Sturgis, EM; Eicher, SA; Spitz, MR; Hong, WK; Wei, Q

Published Date

  • July 1998

Published In

Volume / Issue

  • 4 / 7

Start / End Page

  • 1773 - 1778

PubMed ID

  • 9676854

Pubmed Central ID

  • 9676854

International Standard Serial Number (ISSN)

  • 1078-0432

Language

  • eng

Conference Location

  • United States