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 squamous cell carcinoma (ESCC) and susceptibility may be modified by functional polymorphisms in folate metabolic genes, such as methylenetetrahydrofolate reductase (MTHFR). We here aimed to evaluate associations of MTHFR C677T and A1298C polymorphisms with ESCC. METHODS We searched MEDLINE, EMBASE and the Chinese Biomedical Database and 2 evaluators independently reviewed all the articles identified according to predetermined criteria. RESULTS A total of 15 case-control studies published between 2001 and 2010 were included. When all the studies were pooled, the crude odds ratio (95% CI) of ESCC for individuals carrying MTHFR 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) of 3.31 (0.90-12.17). In smokers, a significantly increased risk of ESCC was observed for those with the MTHFR 677T allele (OR (95% CI)=2.2 (1.31-2.41)). Chinese carrying MTHFR 677T and MTHFR 1298C alleles had a greater increase in ESCC risk than other ethnicities. CONCLUSIONS The present meta-analysis provided evidence that 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 conclusions regarding this polymorphism.