Association of methylenetetrahydrofolate reductase (MTHFR) polymorphisms with genetic susceptibility to gastric cancer: a meta-analysis.

To clarify the influence of MTHFR C677T and A1298C polymorphisms on gastric cancer (GC), a meta-analysis of eight case-control studies (1,584/2,785 cases/controls) was carried out. Overall, there was moderate heterogeneity among studies, and the C677T allele T was associated with a 27% increased risk of GC compared with C allele: the random effects (RE) OR (95% confidence interval in parenthesis) was significant [OR=1.27 (1.13-1.44)]. In East Asians, the association was significant: RE OR=1.28 (1.14-1.44), whereas, in Caucasians it was not significant. Regarding gastric cancer adenocarcinoma (GCA), an association for the allele contrast in East Asians was detected: fixed effects (FE) OR=1.36 (1.18-1.56). The recessive model for allele T produced significant results overall and in East Asians for GC [FE OR=1.47 (1.26-1.72) and FE OR=1.61 (1.32-1.96), respectively] and for GCA [RE OR=1.53 (1.13-2.05) and FE OR=1.70 (1.36-2.12)]. The A1298C polymorphism was associated with GCA in East Asians: the FE OR for the allele contrast (C vs. A) was 1.38 (1.18-1.62), and under a recessive model for allele C, OR=1.62 (1.28-2.06). There were no sources of bias in the selected studies; the differential magnitude of effect in large versus small studies was not significant. In conclusion, there is evidence of association between MTHFR polymorphisms and GC, mainly in East Asians.