Glutathione-S-transferase polymorphisms and risk of squamous-cell carcinoma of the head and neck

Differences in genetic susceptibility to tobacco-induced carcinogenesis app ear to modulate an individual's risk of squamous-cell carcinoma of the head and neck (SCCHN), Risk for SCCHN may be associated with the null alleles o f the carcinogen-metabolizing genes glutathione-S-transferase (GST) TI and GSTMI. In this study, we evaluated the association between GSTMI and GSTTI null genotypes and risk of SCCHN in a matched case-control study of 162 pat ients with SCCHN and 315 healthy controls. Our results showed that 53.1% of cases and 42.9% of controls were null for GSTMI, whereas 32.7% of cases an d 17.5% of controls were null for GSTTI (p < 0.05 and p < 0.001, respective ly). Furthermore, 19.8% of cases but only 7.9% of controls were null for bo th genes (p < 0.001). Multivariate analysis using logistic regression model s, including age, sex, ethnicity, smoking status, alcohol status and CST ge notypes, showed that both of these genotypes remained independent risk fact ors for disease [adjusted odds ratios (ORs) = 1.50 and 2.27, respectively; 95% confidence intervals (Cls) = 1.01-2.23 and 1.43-3.60, respectively). Wh en the genotypes were divided into neither null, either null or both null, there was a dose-response relationship (adjusted OR = 1.50, 95% CI = 0.98-2 .30) for the either-null group and (adjusted OR = 3.64, 95% CI = 1.94-6.84) for the both-null group (p < 0.001, trend test). Our findings suggest that the GSTMI and GSTTI null genotypes are independent risk factors for SCCHN and markers for genetic susceptibility to tobacco-induced carcinogenesis. I nt. J. Cancer (Pred. Oncol.) 84:220-224, 1999. (C) 1999 Wiley-Liss, Inc.