Genetic Polymorphisms of Glutathione S-Transferase Genes GSTM1, GSTT1 and Risk of Hepatocellular Carcinoma

Abstract

BackgroundA number of case-control studies were conducted to investigate the association of glutathione S-transferase (GST) genetic polymorphisms and hepatocellular carcinoma (HCC) risk. However, these studies have yielded contradictory results. We therefore performed a meta-analysis to derive a more precise estimation of the association between polymorphisms on GSTM1, GSTT1 and HCC.Methodology/Prinicpal FindingsPubMed, EMBASE, ISI web of science and the CNKI databases were systematically searched to identify relevant studies. Data were abstracted independently by two reviewers. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to assess the strength of association. Potential sources of heterogeneity were also assessed by subgroup analysis and meta-regression. Funnel plots and Egger’s linear regression were used to test publication bias among the articles. A total of 34 studies including 4,463 cases and 6,857 controls were included in this meta-analysis. In a combined analysis, significantly increased HCC risks were found for null genotype of GSTM1 (OR = 1.29, 95% CI: 1.06–1.58; P = 0.01) and GSTT1 (OR = 1.43, 95% CI: 1.22–1.68; P<10−5). Potential sources of heterogeneity were explored by subgroup analysis and meta-regression. Significant results were found in East Asians and Indians when stratified by ethnicity; whereas no significant associations were found among Caucasians and African populations. By pooling data from 12 studies that considered combinations of GSTT1 and GSTM1 null genotypes, a statistically significant increased risk for HCC (OR = 1.88, 95% CI: 1.41–2.50; P<10−4) was detected for individuals with combined deletion mutations in both genes compared with positive genotypes.Conclusions/SignificanceThis meta-analysis suggests that the GSTM1 and GSTT1 null genotype may slightly increase the risk of HCC and that interaction between unfavourable GSTs genotypes may exist.

Risk Effects of GST Gene Polymorphisms in Patients with Acute Myeloid Leukemia: A Prospective Study

“…The allele frequencies for all the studied GSTs polymorphisms were similar to those reported from Chinese population (Jing et al, 2012;Song et al, 2012). However, the sample size is relative small in our study, and statistical power is insufficient for detecting the effect of GSTs genes on AML risk.…”

Association of GSTTI and GSTM1 variants with acute myeloid leukemia risk

“…The allele frequencies for all of the GST polymorphisms studied were similar to those reported for the Chinese population previously (Jing et al, 2012;Song et al, 2012). However, there were several limitations to our study.…”

Polymorphisms in the GSTT1 and GSTM1 genes are associated with increased risk of preeclampsia in the Mexican mestizo population

“…Specifically, GSTT1 and GSTM1 have been associated with various pathologies including oral cancer, cervical neoplasia, breast cancer, glaucoma, hepatocellular carcinoma, and type 2 diabetes (Gao et al, 2011;Zhang et al, 2011;Song et al, 2012;Sohail et al, 2013;Yi et al, 2013;Yu et al, 2013). Moreover, several studies were previously conducted to assess the role of GST genes in preeclampsia (Zusterzeel et al, 2000;Cetin et al, 2005;Kim et al, 2005;Zhang et al, 2008;Atalay et al, 2012;Saadat et al, 2012), but to date, only a deletion of the GSTP1 gene has been associated with the pathology (Zusterzeel et al, 2000).…”