title: 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 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.
authors.affiliation: State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai, PR China.
authors.forename: Ke
authors.initials: K
authors.lastname: Yu
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Jiyuan
authors.initials: J
authors.lastname: Zhang
authors.forename: Chao
authors.initials: C
authors.lastname: Dou
authors.forename: Shaohua
authors.initials: S
authors.lastname: Gu
authors.forename: Yi
authors.initials: Y
authors.lastname: Xie
authors.forename: Yumin
authors.initials: Y
authors.lastname: Mao
authors.forename: Chaoneng
authors.initials: C
authors.lastname: Ji
mesh_terms: D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000235:genetics*; D019943:Amino Acid Substitution / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D005060:Europe; D018740:Genetic Heterogeneity; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D009369:Neoplasms / Q000201:enzymology* / Q000235:genetics*; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017594:Publication Bias
chemical_list: D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase