A single-nucleotide polymorphism (rs1805087) in the methionine synthase (METH) gene increases the risk of prostate cancer

Abstract

Methionine synthase (METH, i.e., MTR) is a key enzyme in the folate pathway, which plays a critical role in the synthesis, repair, and methylation of DNA. The association between METH gene polymorphisms and prostate cancer susceptibility remains ambiguous. Thus, we performed an updated meta-analysis of METH singlenucleotide polymorphism rs1805087 involving 12 independent case-control studies comprising 9986 prostate cancer patients and 40134 controls. The odds ratio and 95% confidence intervals were applied to evaluate the relation of this single-nucleotide polymorphism with prostate cancer. Statistical analysis was performed in STATA 11.0. A significant association was found between rs1805087 and increased prostate cancer risk, overall and with Hardy-Weinberg equilibrium. In subgroup analyses (based on ethnicity, source of control, genotyping methods, or publication status), similar associations were observed (e.g., genotype GA vs. AA: odds ratio 1.19, 95% confidence interval 1.01-1.40 among whites; G allele vs. A allele: odds ratio 1.14, 95% confidence interval 1.02-1.28 among hospital-based controls). Thus, the common polymorphism (rs1805087) of METH may be associated with increased prostate cancer risk. Further studies with a larger sample size and detailed gene-environment interactions should be conducted to identify the role of METH polymorphisms in prostate cancer susceptibility.