Previous studies have investigated the association of the rs1805087 A/G variant of Methionine synthase gene with the susceptibility to prostate cancer (PCa). Nevertheless, the conclusions remain divergent. We performed a systemic analysis with odds ratios (ORs) and 95% confidence intervals (95% CIs) to assess Methionine synthase rs1805087 A/G variant and PCa risk. Furthermore, we utilized in silico analysis to investigate the relationship between Methionine synthase expression and the overall survival (OS) time. Totally, 10,666 PCa patients and 40,750 controls were included. We observed that Methionine synthase rs1805087 A/G variant is associated with an elevated risk of PCa (G-allele vs. A-allele: OR = 1.06, 95% CI = 1.01–1.11, P = 0.013; heterozygous model: OR = 1.08, 95% CI = 1.02–1.14, P = 0.009; dominant model: OR = 1.08, 95% CI = 1.02–1.14, P = 0.007). During stratified analysis, similar results were obtained in Asian populations, hospital-based, high quality studies and that with large sample size. Moreover, in silico analysis indicated the Methionine synthase expression is down-regulated in both young and old PCa subjects ( P < 0.05). Compared with the normal subjects, the down-regulated expression of Methionine synthase was found in PCa cases with Gleason score 6 to 9. Our study showed that Methionine synthase rs1805087 A/G variant may be associated with susceptibility of PCa, especially in Asian populations, hospital-based studies and that with high quality and large sample size. Furthermore, Methionine synthase rs1805087 A/G variant may be related to the prognosis of PCa.
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