Methionine synthase A2756G polymorphism and cancer risk: a meta-analysis

Polymorphisms in methionine synthase ( MTR ) gene may be involved in carcinogenesis by affecting DNA methylation. However, association studies on MTR A2756G polymorphism in cancers have reported conflicting results. Therefore we performed a meta-analysis to better assess the associations. A total of 24 896 cancer patients and 33 862 controls from 52 articles for MTR A2756G were investigated. Overall, individuals carrying MTR 2756GG genotype had a subtly reduced cancer risk under a recessive genetic model (odds ratio (OR), 0.92; P =0.053; 95% confidence interval (95% CI), 0.84–1.00; I 2 =0.0%; P heterogeneity =0.61). In the subgroup analyses by ethnicity, 2756GG was associated with a significantly reduced cancer risk in European populations (OR, 0.83; P =0.001; 95% CI, 0.74–0.93; I 2 =0.0%; P heterogeneity =0.99). However, in Asian populations, a significantly elevated association between 2756GG genotype and cancer risk was observed (OR, 1.33; P =0.012; 95% CI, 1.06–1.65; I 2 =0.0%; P heterogeneity =0.50). In studies stratified by tumor site, there was a significantly reduced risk of acute lymphoblastic leukemia (ALL) (OR, 0.54; P =0.049; 95% CI, 0.29–1.00; I 2 =10.7%; P heterogeneity =0.33) and colorectal cancer (OR, 0.63; P =0.004; 95% CI, 0.47–0.87; I 2 =0.0%; P heterogeneity =0.73) in European populations. Our study indicates that MTR A2756G polymorphism is a candidate gene polymorphism for cancer susceptibility regardless of environmental factors. Large-scale, well-designed, and population-based studies are required to further investigate gene–gene and gene–environment interactions on MTR A2756G polymorphism and tissue-specific cancer risk in an ethnicity-specific population.