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

Abstract

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 metaanalysis 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; P¼0.053; 95% confidence interval (95% CI), 0.84-1.00; I 2 ¼0.0%; P heterogeneity ¼0.61). In the subgroup analyses by ethnicity, 2756GG was associated with a significantly reduced cancer risk in European populations (OR, 0.83; P¼0.001; 95% CI, 0.74-0.93; I 2 ¼0.0%; P heterogeneity ¼0.99). However, in Asian populations, a significantly elevated association between 2756GG genotype and cancer risk was observed (OR, 1.33; P¼0.012; 95% CI, 1.06-1.65; I 2 ¼0.0%; P heterogeneity ¼0.50). In studies stratified by tumor site, there was a significantly reduced risk of acute lymphoblastic leukemia (ALL) (OR, 0.54; P¼0.049; 95% CI, 0.29-1.00; I 2 ¼10.7%; P heterogeneity ¼0.33) and colorectal cancer (OR, 0.63; P¼0.004; 95% CI, 0.47-0.87; I 2 ¼0.0%; P heterogeneity ¼0.73) 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.

Strong association of methylenetetrahydrofolate reductase gene C677T polymorphism with hypertension and hypertension-in-pregnancy in Chinese: a meta-analysis

“…In contrast, controls drawn from the general population might be representative of the true population of those without the disease. 36 Even so, population selection bias is unlikely to affect the validity of our findings, because genotype frequencies of C677T polymorphism respected Hardy-Weinberg equilibrium in all control groups. It is thus speculated that in this meta-analysis, the magnitude of association between MTHFR C677T and hypertension might be overestimated in the overall OR estimates.…”

Lack of association between Cyclin D1 gene G870A polymorphism and esophageal cancer: evidence from a meta-analysis

“…Different genetic backgrounds may cause this discrepancy or different populations may have different linkage disequilibrium patterns. A polymorphism may be in close linkage with another nearby causal variant in one ethnic population but not in another (Yu et al, 2010). Thus, it is reasonable to hypothesize that the CCND1 A870G polymorphism might be in close linkage with different nearby causal variants in different populations.…”

Meta-analysis demonstrates lack of an association of microsomal epoxide hydrolase 1 polymorphisms with esophageal cancer risk

“…On the one hand, there were striking differences in terms of 113Tyr and 139His allele frequency in patients between Canadians and Chinese (27.72 vs 48.38% in 113Tyr,19.80 vs 89.86% in 139His), suggesting that different genetic backgrounds may cause this discrepancy or that different populations may have different linkage disequilibrium patterns. A polymorphism may be in close linkage with another nearby causal variant in one ethnic population but not in another (Yu et al, 2010). The EPHX1 gene Tyr113His and His139Arg polymorphisms may be in close linkage with different nearby causal variants in different populations.…”