The 677C>T (rs1801133) Polymorphism in the MTHFR Gene Contributes to Colorectal Cancer Risk: A Meta-Analysis Based on 71 Research Studies

BACKGROUND: The 677C>T polymorphism of methylenetetrahydrofolate reductase (MTHFR) gene is considered to have a significant effect on colorectal cancer susceptibility, but the results are inconsistent. In order to investigate the association between the MTHFR 677C>T polymorphism and the risk of colorectal cancer, a meta-analysis was held based on 71 published studies. METHODS: Eligible studies were identified through searching the MEDLINE, EMBASE, PubMed, Web of Science, Chinese Biomedical Literature database (CBM) and CNKI database. Odds ratios (OR) and 95% confidence intervals (CIs) were used to assess the association. The statistical heterogeneity across studies was examined with x(2)-based Q-test. Begg's and Egger's test were also carried out to evaluate publication bias. Sensitive and subgroup analysis were also held in this meta-analysis. RESULTS: Overall, 71 publications including 31,572 cases and 44,066 controls were identified. The MTHFR 677 C>T variant genotypes are significantly associated with increased risk of colorectal cancer. In the stratified analysis by ethnicity, significantly increased risks were also found among Caucasians for CC vs TT (OR = 1.076; 95%CI = 1.008–1.150; I(2) = 52.3%), CT vs TT (OR = 1.102; 95%CI = 1.032–1.177; I(2) = 51.4%) and dominant model (OR = 1.086; 95%CI = 1.021–1.156; I(2) = 53.6%). Asians for CC vs TT (OR = 1.226; 95%CI = 1.116–1.346; I(2) = 55.3%), CT vs TT (OR = 1.180; 95%CI = 1.079–1.291; I(2) = 36.2%), recessive (OR = 1.069; 95%CI = 1.003-1.140; I(2) = 30.9%) and dominant model (OR = 1.198; 95%CI = 1.101-1.303; I(2) = 52.4%), and Mixed populations for CT vs TT (OR = 1.142; 95%CI = 1.005-1.296; I(2) = 0.0%). However, no associations were found in Africans for all genetic models. CONCLUSION: This meta-analysis suggests that the MTHFR 677C>T polymorphism increases the risk for developing colorectal cancer, while there is no association among Africans found in subgroup analysis by ethnicity.