Folate intake, methylenetetrahydrofolate reductase polymorphisms, and risk of esophageal cancer

Aim: Genetic and environmental factors may play roles in the pathogenesis of esophageal cancer and susceptibility may be modified by functional polymorphisms in folate metabolic genes, such as methylenetetrahydrofolate reductase (MTHFR). We here evaluated associations of the MTHFR C677T polymorphism and folate intake with esophageal cancer. Methods: A matched hospital-based case-control study with 155 esophageal cancer and 310 non-cancer controls was conducted in a Chinese population with gene-environment interactions evaluated between the MTHFR C667T polymorphism and drinking and smoking, as well as folate intake. Results: Individuals carrying MTHFR 667CT [adjusted odds ratio (OR), 1.95; 95% confidence interval (CI), 1.23-2.62] and TT [adjusted odds ratio (OR), 3.36; 95% confidence interval (CI), 1.46-8.74] had significantly increased esophageal cancer risk compared with those with MTHFR 667CC genotype. Folate intake was seen to have non-significant preventive effect. In former, moderate and heavy drinkers, a high esophageal cancer risk was observed for those with an MTHFR 677T allele genotype [ORs: 5.0(1.29-18.88), 3.70(1.83-7.66) and 5.77(2.11-15.72), respectively]. Significant interaction was found for moderate-heavy drinking and the MTHFR 677T allele genotype for esophageal cancer risk (p<0.05). Significant increased risk was also found in moderate and heavy smokers with the two genotypes [ORs: 3.58(1.64-7.80) and 4.51(1.15-17.78), respectively]. High folate intake and MTHFR 677TT was associated with a non-significant tendency for decreased esophageal cancer risk. Conclusion: Our finding supports the hypothesis that MTHFR C667T polymorphisms play a role in pathogenesis of esophageal cancer in the Chinese population.