Association between the MTHFR C677T polymorphism and gastric cancer susceptibility: A meta-analysis of 5,757 cases and 8,501 controls.

Current data regarding the association between the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and the risk of developing gastric cancer are insufficient to draw definite conclusions. Therefore, the present meta-analysis was conducted to achieve a more precise estimation of the association. MEDLINE, EMBASE and Wanfang database searches resulted in the identification of 28 eligible studies describing 5,757 cases and 8,501 controls. The strength of the association between the MTHFR C677T polymorphism and gastric cancer risk were evaluated using crude odds ratios (ORs), with 95% confidence intervals (CIs). The pooled ORs were determined using homozygous (TT vs. CC), heterozygous (CT vs. CC), dominant (TT+CT vs. CC) and recessive (TT vs. CC+CT) models. When all studies were pooled into the meta-analysis, significant associations were identified between the MTHFR C677T polymorphism and the risk of gastric cancer (homozygous model: OR, 1.39; 95% CI, 1.20-1.62; heterozygous model: OR, 1.18; 95% CI, 1.05-1.32; dominant model: OR, 1.23; 95% CI, 1.10-1.38; recessive model: OR, 1.26; 95% CI, 1.12-1.42). Stratification of the data by ethnicity identified a statistically significantly elevated risk of gastric cancer in Asian MTHFR C677T polymorphism populations (homozygous model: OR, 1.64; 95% CI, 1.43-1.90; heterozygous model: OR, 1.30; 95% CI, 1.16-1.45; dominant model: OR, 1.39; 95% CI, 1.25-1.54; recessive model: OR, 1.41; 95% CI, 1.25-1.51), but not in Caucasian populations (homozygous model: OR, 1.15; 95% CI, 0.89-1.48; heterozygous model: OR, 1.03; 95% CI, 0.84-1.25; dominant model: OR, 1.05; 95% CI, 0.86-1.28; recessive model: OR, 1.09; 95% CI, 0.91-1.31). Following adjustment for heterogeneity, the current meta-analysis demonstrated that the MTHFR C677T polymorphism was not associated with the risk of gastric cancer in Caucasian individuals. Furthermore, no evidence of publication bias was observed. Thus, the current meta-analysis indicates that the MTHFR C677T allele may be a low-penetrant risk factor for the development of gastric cancer in Asian populations.