Lack of Association between Methionine Synthase A2756G Polymorphism and Digestive System Cancer Risk: Evidence from 39327 Subjects

BACKGROUND Polymorphisms in genes involved in the metabolism of folate and methyl groups have been implicated with risk of digestive system cancer. Methionine synthase (MTR) plays a central role in folate metabolism, thereby affecting DNA methylation. The association between A2756G polymorphism (rs1805087) in MTR and digestive system cancer susceptibility was inconsistent in previous studies. To investigate this inconsistency, we performed this meta-analysis. METHODS Databases including Pubmed, EMBASE, ISI Web of Science and China National Knowledge Infrastructure (CNKI) were searched to find relevant studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association. Potential sources of heterogeneity were also assessed by subgroup analysis and meta-regression. RESULTS A total of 29 articles with 15,368 patients and 23,959 controls were included. We found no association between MTR A2756G polymorphism and digestive system cancer in overall population (G allele: OR = 1.03, 95% CI = 0.98-1.09, P = 0.25; dominant model: OR = 1.03, 95% CI = 0.97-1.10, P = 0.33; recessive model: OR = 1.02, 95% CI = 0.89-1.17, P = 0.79). In the stratified analyses according to cancer type, sample size and genotyping method, no evidence of any gene-disease association was obtained in almost all genetic models. However, marginal significant associations were found for East Asians and hospital-based studies. CONCLUSIONS This meta-analysis suggests that there is no significant association between the MTR A2756G polymorphism and digestive system cancer risk.