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

Aging (Albany NY). 2018 Oct 18;10(10):2741-2754. doi: 10.18632/aging.101584.

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 single-nucleotide 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.

Keywords: meta-analysis; methionine synthase; polymorphism; prostate cancer; susceptibility.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / genetics*
  • Biomarkers, Tumor / genetics*
  • Case-Control Studies
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Humans
  • Male
  • Polymorphism, Single Nucleotide*
  • Prostatic Neoplasms / enzymology
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / pathology
  • Risk Assessment
  • Risk Factors

Substances

  • Biomarkers, Tumor
  • 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase
  • MTR protein, human