Systematic Review on the Relationship between Genetic Polymorphisms of Methylenetetrahydrofolate Reductase and Esophageal Squamous Cell Carcinoma

Background: Both genetic and environmental factors play roles in pathogenesis of esophageal squamouscell carcinoma (ESCC) and susceptibility may be modified by functional polymorphisms in folate metabolicgenes, such as methylenetetrahydrofolate reductase (MTHFR). We here aimed to evaluate associations ofMTHFR C677T and A1298C polymorphisms with ESCC.
Methods: We searched MEDLINE, EMBASE andthe Chinese Biomedical Database and 2 evaluators independently reviewed all the articles identified accordingto predetermined criteria.
Results: A total of 15 case-control studies published between 2001 and 2010 wereincluded. When all the studies were pooled, the crude odds ratio (95% CI) of ESCC for individuals carryingMTHFR 677 CT and TT genotypes, as compared to CC, were 1.39 (1.11-1.75) and 1.79 (1.31-2.43), respectively.Individuals with MTHFR 1298CC showed non-significantly increased risk of ESCC, with an OR (95%CI) of3.31(0.90-12.17). In smokers, a significantly increased risk of ESCC was observed for those with the MTHFR677T allele (OR (95% CI)=2.2 (1.31-2.41)). Chinese carrying MTHFR 677T and MTHFR 1298C alleles had agreater increase in ESCC risk than other ethnicities.
Conclusions: The present meta-analysis provided evidencethat MTHFR 677CT/TT plays a carcinogenic role in ESCC, and its effect is modified by tobacco and ethnicity.The small number of subjects with the MTHFR 1299C allele genotype in published studies limits conclusionsregarding this polymorphism.