Abstract
BackgroundGlutathione 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.MethodsThis 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.ResultsA 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, Pheterogeneity<0.001). Sub-group analysis suggested that the significant association was only observed in Asians (OR=1.273, 95%: 1.137-1.426, Pheterogeneity = 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, Pheterogeneity=0.065), while no association was found among H. pylori negative population (OR=0.969, 95% CI: 0.618-1.521, Pheterogeneity=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.ConclusionsIn 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.
Highlights
Glutathione S-transferases M1 (GSTM1) is an important phase II metabolizing enzyme
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
The following medical subheadings (MeSH) and key words were utilized during database searching: “glutathione Stransferase M1” or “GSTM1”, “polymorphisms, single nucleotide” or “polymorphism”, and “stomach neoplasms” or
Summary
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. This study was carried out and reported in agreement with the PRISMA guidelines for systematic reviews and metaanalyses [13] Eligible case-control studies were extracted by searching databases and manual search of references of relative articles and reviews. A comprehensive literature search was carried out using electronic databases of PubMed and EMBASE. The following medical subheadings (MeSH) and key words were utilized during database searching: “glutathione Stransferase M1” or “GSTM1”, “polymorphisms, single nucleotide” or “polymorphism”, and “stomach neoplasms” or “gastric cancer”. Alternative spellings of these key words were considered. References of related studies and reviews were manually searched for additional studies
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