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PLoS One. 2013;8(2):e55332. doi: 10.1371/journal.pone.0055332. Epub 2013 Feb 20.

The 677C>T (rs1801133) polymorphism in the MTHFR gene contributes to colorectal cancer risk: a meta-analysis based on 71 research studies.

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Department of Medical Oncology, the First Hospital of China Medical University, Shenyang, Liaoning, P.R. China.



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.


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.


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.


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.

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