Methylenetetrahydrofolate Reductase C677T and A1298C Polymorphisms and Gastric Cancer: A Meta-analysis

Background and AimsCase/control studies that investigated the association between gastric cancer and the MTHFR C677T and A1298C polymorphisms so far have provided controversial results. To clarify the effect of MTHFR polymorphisms on the risk of gastric cancer, a meta-analysis was performed.MethodsWe performed a computerized search of the PubMed database for relevant reports before September 2009. No language restrictions were added. The associated literature was acquired through a deliberate retrieval strategy and selected based on the established inclusion criteria for publications.ResultsThe studies provided 4070/6462 cases/controls for C677T and 1923/3561 cases/controls for A1298C. There was significant heterogeneity (p = 0.015, I2 = 44.0%) among the 22 studies, and the RE model showed that the C677T allele T was associated with a 17.3% increased risk of gastric cancer compared with the allele C (RE OR = 1.173 [1.051–1.274]). Results from the subgroup analysis showed an increased risk in Asians (fixed-effect, FE OR 1.277 [1.179–1.382]), but not in Caucasians (random-effect, RE OR 1.194 [0.866–1.646]). The contrast of homozygotes (TT vs. CC) produced significant results in Asians (FE OR 1.611 [1.366–1.901]), whereas, in Caucasians, it was not significant (RE OR 1.385 [0.754–2.544]). In regard to the A1298C polymorphism, there was no heterogeneity among the 11 studies comparing the C vs. the A allele (p = 0.352, I2 = 9.7%), but no significant association was detected.ConclusionsThe evidence from our meta-analysis supports that TT genotype of MTHFR C677T polymorphism contributes to susceptibility to gastric cancer, but no significant association was detected for CC genotype of MTHFR A1298C.