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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.

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