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.
Ho, T; Zhao, C; Zheng, R; Liu, Z; Wei, Q; Sturgis, EM
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