Methylenetetrahydrofolate reductase C677T and A1298C polymorphisms and gastric cancer susceptibility: an updated meta-analysis

Widely regarded as one of the most prevalent malignancies worldwide, gastric cancer (GC) is a common clinical condition of the digestive system. Reviewing 14 meta-analyses that eval-uated the association between methylenetetrahydrofolate reductase (MTHFR) gene poly-morphisms and GC risk, we observed inconsistent results, and the credibility of the signifi-cant correlation between the statistical results was ignored. With the aim of further explor-ing the association between MTHFR C677T and A1298C and the risk of GC, we searched electronic databases, pooling 43 relevant studies and calculating odds ratios (ORs) and cor-responding 95% confidence intervals (CIs) for each of the five genetic models. Subgroup and regression analyses were performed to look for sources of heterogeneity and publica-tion bias was assessed by funnel plots. To assess the plausibility of statistically significant associations, we used the FPRP test and the Venice criteria. Overall data analysis showed that MTHFR C677T polymorphism was significantly associated with GC risk, especially in Asians, while MTHFR A1298C polymorphism was not associated with GC risk. However, in subgroup analysis by hospital-based controls, we found that MTHFR A1298C might be a protective factor for GC. After credibility assessment, the statistical association between MTHFR C677T and GC susceptibility study was classified as 'less credible positive result', while the result of MTHFR A1298C was considered unreliable. In summary, the present study strongly suggests that MTHFR C677T and A1298C polymorphisms are not significantly as-sociated with the GC risk.

Automated summary

Gastric cancer is a common malignancy of the digestive system. In this study, inconsistent results were found when evaluating the association between MTHFR gene polymorphisms and gastric cancer risk. However, further analysis showed that MTHFR C677T polymorphism was significantly associated with gastric cancer risk, especially in Asians, while MTHFR A1298C polymorphism was not associated with gastric cancer risk.