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

Background: A 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 Findings: PubMed, 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% Cls) 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/Significance: This 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.