Glutathione-S-Transferase Polymorphisms and Risk of Differentiated Thyroid Carcinomas

Abstract

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-µ1 (GSTM1) (P=.52), and 25.4% of the DTC subjects and 20.6% of the controls were null for the GST-1 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.

Involvement of CYP1A1, GST, 72TP53 polymorphisms in the pathogenesis of thyroid nodules

“…The relationship between genotype and phenotype in CYP1A1m1 and CYP1A1m2 is not yet fully understood. Our study also demonstrated that the GSTM1 and GSTT1 null genotypes were distinct between patients and controls, which is consistent with some studies (Morari et al, 2002;Hernández et al, 2003;Gaspar et al, 2004;Bufalo et al, 2006;Ho et al, 2006;Gonçalves et al, 2007;Lemos et al, 2008;Siraj et al, 2008) involving these genotypes and the risk of developin benign and malignant thyroid diseases.…”

“…These protein dimers bind electrophilic molecules and free radicals in order to reduce them to products that are nontoxic to the organism. According to previous studies (Morari et al, 2002;Gaspar et al, 2004;Ho et al, 2006) individuals with the null genotypes for GSTM1 and GSTT1 could have an increased susceptibility to thyroid cancer. In addition, it was suggested that the combination of GSTM1, GSTT1 and GSTP1 polymorphisms promoted a moderate increased risk of thyroid cancer, especially PTC (Siraj et al, 2008).…”

Genetic polymorphism of CYP2D6 influences susceptibility to papillary thyroid cancer

“…Polymorphisms of other xenobiotic-metabolizing enzymes such as glutathione S-transferase mu-1 and theta-1 have also been associated with different susceptibilities to thyroid cancer [19][20][21] and this greatly supports the role of xenobiotic-metabolizing enzymes in thyroid carcinogenesis. A role for chemical carcinogenesis in PTC has not yet been established in humans, although animal experiments have identified several compounds with the potential to cause thyroid tumours in vivo .…”

Sistema Glutation-S-Transferase como fator prognóstico no carcinoma papilífero da tireoide

“…Isso poderia estar confirmando a hipótese do GST ausente ser um fator de melhor prognóstico, pois o GST confere proteção tanto a célula normal como para a neoplásica, e por isso poderia estar relacionado com uma maior agressividade tumoral. No entanto devemos levar em consideração o fato de que o carcinoma papilífero de tireoide apresenta em geral boa evolução clinica, portanto espera-se que haja uma maior frequência de pacientes considerados de baixo risco, independentemente de suas características genéticas 24 . Rigual et al (2005) estudaram 33 pacientes com carcinoma papilífero da tireoide e encontraram uma associação positiva entre a deleção do gene GSTM1 e o risco de recidiva e mortalidade da doença, avaliado pelo sistema GAMES (Memorial Sloan-Kettering) 25 .…”