The GSTM1 Null Genotype Increased Risk of Gastric Cancer: A Meta-Analysis Based on 46 Studies

Background: Glutathione S-transferases M1 (GSTM1) is an important phase II metabolizing enzyme. The null genotype of GSTM1 causes total loss of GSTM1 enzyme activity and numerous studies have investigated the association between GSTM1 null genotype and gastric cancer risk. Methods: This meta-analysis was designed to investigate the relationship between GSTM1 null genotype and susceptibility to gastric cancer and assess the influence of Helicobacter pylori infection, smoking, Lauren's classification, and other factors. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to estimate the association strength. Results: A total of 46 eligible studies were indentified and analyzed in this meta-analysis, including 8138 cases of gastric cancer and 13867 controls. Pooled results showed that the GSTM1 null genotype was associated with a significantly increased risk of gastric cancer (OR=1.217, 95% CI: 1.113-1.331, P-heterogeneity<0.001). Sub-group analysis suggested that the significant association was only observed in Asians (OR=1.273, 95%: 1.137-1.426, P-heterogeneity = 0.002), but not in Caucasians. The increased risk was found among H. pylori positive population (OR=1.928, 95% CI: 1.028-3.615, P-heterogeneity = 0.065), while no association was found among H. pylori negative population (OR=0.969, 95% CI: 0.618-1.521, P-heterogeneity=0.168). For smoking status, the GSTM1 null genotype increased risk of gastric cancer in both ever-smokers and non-smokers. Source of control, sample size, location of tumor and Lauren's classification did not modify the association. Conclusions: In this meta-analysis based on 46 epidemiological studies, we show that the GSTM1 null genotype is associated with an increased risk of gastric cancer among Asians but not among Caucasians. H. pylori infection but not smoking status could modify the association.