5,10-Methylenetetrahydrofolate Reductase Polymorphisms and Colon Cancer Risk: a Meta-analysis

  • Fang, Xin-Yu (Epidemiology and Statistics, School of Public Health, Anhui Medical University) ;
  • Xu, Wang-Dong (Epidemiology and Statistics, School of Public Health, Anhui Medical University) ;
  • Huang, Qian (Epidemiology and Statistics, School of Public Health, Anhui Medical University) ;
  • Yang, Xiao-Ke (Epidemiology and Statistics, School of Public Health, Anhui Medical University) ;
  • Liu, Yan-Yan (Epidemiology and Statistics, School of Public Health, Anhui Medical University) ;
  • Leng, Rui-Xue (Epidemiology and Statistics, School of Public Health, Anhui Medical University) ;
  • Pan, Hai-Feng (Epidemiology and Statistics, School of Public Health, Anhui Medical University) ;
  • Ye, Dong-Qing (Epidemiology and Statistics, School of Public Health, Anhui Medical University)
  • Published : 2014.10.23


Previous studies investigating the association between 5,10-methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and colon cancer risk have generated conflicting results. The aim of our meta-analysis was to clarify the precise association. A systematic literature search was conducted to identify all relevant studies. Pooled odds ratio (ORs) with 95% confidence interval (CI) were used to estimate the strength of the association. In this meta-analysis, a total of 13 articles, involving 5,386 cases and 8,017 controls met the inclusion criteria. Overall, a significant association was found between colon cancer risk and the MTHFR C667 polymorphism (TT vs CC+CT: OR=0.79; 95%CI=0.65-0.96; p=0.017). Stratification by ethnicity revealed that MTHFRC667 was associated with colon cancer risk in the non-Asian group (TT vs CC+CT:OR=0.77, 95%CI=0.68-0.89, p=0.000; TT vs CC: OR=0.84, 95%CI=0.73-0.97, p=0.016). Stratification by source of control indicated that MTHFR C667 also correlated with colon cancer risk in the population-based subgroup (TT vs CC: OR=0.85, 95%CI=0.74-0.97, p=0.017; TT vs CC+CT: OR=0.78, 95%CI=0.68-0.89, p=0.000) and hospital-based subgroup (TT vs CC+CT: OR=0.65, 95%CI=0.49-0.86, p=0.003). However, risk was significantly increased for MTHFR A1298C polymorphisms and colon cancer risk in hospital-based studies (C vs A: OR=1.52, 95%CI=1.26-1.83, p=0.000; CC+AC vs AA: OR=1.93, 95%CI=1.47-2.49, p=0.000) but reduced in population-based studies (CC vs AA: OR=0.83, 95%CI=0.70-0.99, p=0.042). In conclusion, the results of our meta-analysis suggest that the MTHFR C667 polymorphism is associated with reduced colon cancer risk, especially for non-Asian populations.


5, 10-methylenetetrahydrofolate reductase;polymorphisms;colon cancer;meta-analysis;non-Asians


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