Meta-analysis of the Relationship between the Metholenetetrahydrofolate Reductase C677T Genetic Polymorphism, Folate Intake and Esophageal Cancer


Objective: To evaluate the effect of the methylenetetrahydrofolate reductase C677T genetic polymorphism(MTHFR C677T) and folate intake on the risk of esophageal cancer.
Methods: A total of 17 studies (3,277 casesand 4,661 controls) regarding MTHFR C677T and 6 studies (1,817 cases and 7,678 controls) regarding folateintake published between 2001 and 2011 were identified through researching MEDLINE, EMBASE and theChinese Biomedical Database. The data of the last search was February 2011. A meta-analysis was performedto obtain summary estimated odd ratios and 95% confidence intervals of folate intake and MTHFR C677T foresophageal cancer.
Results: A significant association was seen between MTHFR 677 CT [adjusted OR (95%CI)=1.55(1.28-1.88)] and TT [crude OR (95% CI)=1.63(1.24-2.15)] genotypes and esophageal cancer. Folateintake was seen to have a preventive effect on esophageal cancer [OR (95% CI)=0.60(0.50-0.70)]. Non-drinkerswith MTHFR 677 CT and TT showed light esophageal cancer risk, and higher esophageal cancer risk was foundamong smokers. Also, the MTHFR 677 CT and TT genotypes were associated with light esophageal cancer riskin non-drinkers and a higher risk in drinkers. The meta-regression analysis showed the effect of MTHFR 677CT and TT increased with the level of alcohol and tobacco consumption. The MTHFR 677 TT genotype showeda decreased risk of esophageal cancer in the high folate intake group.
Conclusion: MTHFR 677CT/TT increasethe risk of esophageal cancer, and the effects are greatly modified by alcohol, tobacco and folate intake. Folateintake was seen to have a preventive effect on developing esophageal cancer.