Glutathione S-transferase polymorphisms and risk of differentiated thyroid carcinomas: a case-control analysis.

OBJECTIVE To determine the association between glutathione S-transferase (GST) polymorphisms and the risk of differentiated thyroid carcinoma (DTC) and benign thyroid tumors. DESIGN Case-control study. SETTING Tertiary care cancer center. PATIENTS Two hundred one patients with DTC, 103 patients with benign thyroid tumors, and 680 cancer-free control subjects. MAIN OUTCOME MEASURES Results of a polymerase chain reaction-based assay for genotyping. A multivariate logistic regression analysis was performed with adjustment for age, sex, ethnicity, tobacco use, and alcohol use. RESULTS The patients with DTC were younger, more likely to be female and nonwhite, and less likely to smoke or consume alcohol than the controls. Overall, 55.2% of the DTC cases and 52.6% of the controls were null for the gene for GST-mu1 (GSTM1) (P = .52), and 25.4% of the DTC subjects and 20.6% of the controls were null for the GST-theta1 gene (GSTT1) (P = .15). However, 15.9% of the DTC cases but only 9.4% of the controls were null for both genes (P = .009). In addition, the results of the adjusted multivariate regression analysis suggested that having both null genotypes was associated with an increased risk for DTC (odds ratio [OR], 2.1 [95% confidence interval, 1.3-3.5; P = .003]). This was particularly true for women (OR, 2.5), current smokers (OR, 3.6), and nonwhites (OR, 5.6). A similar analysis demonstrated a nonsignificant association between these genotypes and benign thyroid tumors (OR, 1.5 [95% confidence interval, 0.7-3.0; P=.30). CONCLUSIONS Our results suggest that the simultaneous presence of the GSTM1- and GSTT1-null genotypes is a susceptibility factor for DTC. Such knowledge may ultimately help refine cancer prevention efforts; however, larger studies are needed to verify these findings.