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 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.

The Role of Genetic Polymorphisms in the Diagnosis and Management of Prostate Cancer: An Update

“…This polymorphism is the most common mutation of the METH gene and involves the A2756G substitution, which leads an aspartic acid to glycine transition at position 919 of the protein. Therefore, subjects carrying the METH G-allele might have an increased PCa risk (15,16). Another study reported that different SNPs are correlated with PCa predisposition; in particular, the variants rs7000448, rs1048169, rs2961144, rs4430796, rs12500426, rs2066827 and rs114798100 seem to correlate with PCa incidence (17).…”

Cysteine as a Carbon Source, a Hot Spot in Cancer Cells Survival

“…Moreover, the relevance of one carbon metabolism is also highlighted by the association between the levels of folate in peripheral blood, DNA methylation and colorectal tumor staging ( 61 ). Accordingly, the existence of polymorphisms and the increased expression or activity of enzymes participating in one-carbon metabolism are considered markers for highly proliferative and aggressive cancer phenotypes and chemoresistance ( 57 , 62 , 63 ).…”

Polymorphism of folate cycle genes as a risk factor of hyperhomocysteinemia

“…Интерес к генетическим вариантам генов, кодирующих ферменты фолатного цикла, связан с множеством публикаций, описывающих связь различных SNP с частотой самых различных заболеваний. Так, в литературе приведены публикации о связи SNP генов фолатного цикла с риском развития сосудистых заболеваний, онкологических заболеваний, акушерско-гинекологической патологии и бесплодия [16,17,[24][25][26][27][28][29][30][31].…”