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.