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-μ 1 (GSTM1) (P = .52), and 25.4% of the DTC subjects and 20.6% of the controls were null for the GST-θ1 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.