MTR D919G variant is associated with prostate adenocarcinoma risk: evidence based on 51106 subjects.

OBJECTIVE Several case-control studies have identified the association of the D919G polymorphism of the methionine synthase (MTR) gene with the risk of prostate adenocarcinoma (PRAD). However, the results were inconclusive. MATERIALS AND METHODS Odds ratios (ORs) with corresponding 95% confidence intervals (95% CIs) were evaluated to assess the correlation between MTR D919G variant and PRAD risk. In addition, in silico tools were used to demonstrate the relationship between MTR expression and PRAD risk and survival time. RESULTS The overall results from 10,617 PRAD cases and 40,489 control participants indicated the association of the MTR D919G variant with an increased risk of PRAD (allelic contrast: OR = 1.06, 95% CI = 1.01 - 1.11; GA vs. AA: OR = 1.08, 95% CI = 1.02 - 1.14; GG+GA vs. AA: OR = 1.08, 95% CI = 1.02 - 1.14). The stratified analysis yielded similar results for hospital based studies and those with larger sample sizes. Finally, the in silico results revealed lower MTR expression in PRAD tissue than in normal tissue (transcripts per million = 2.68 vs. 3.34, p<0.05). Furthermore, patients with high MTR expression and Gleason score = 6 exhibited reduced survival time (p<0.0001). CONCLUSIONS Our study indicated that the MTR D919G variant is associated with elevated risk to PRAD, especially for Asian descendants and hospital based studies. Moreover, the MTR D919G variant might be related to PRAD prognosis.