Methylenetetrahydrofolate reductase C677T polymorphism in patients with gastric and colorectal cancer in a Korean population

We conducted a population-based large-scale case-control study involving 2,213 patients with newly diagnosed gastric cancer, 1,829 patients with newly diagnosed colorectal cancer, and 1,700 healthy controls. Genotyping was performed with peripheral blood DNA for MTHFR C677T polymorphisms. The statistical significance was estimated by logistic regression analysis.The MTHFR C677T frequencies of CC, CT, and TT genotypes were 35.2%, 47.5%, and 17.3% among stomach cancer, 34%, 50.5%, and 15.5% in colorectal cancer, and 31.8%, 50.7%, and 17.5% in the controls, respectively. The MTHFR 677TT genotype showed a weak opposite association with colorectal cancer compared to the homozygous CC genotype [adjusted age and sex odds ratio (OR) = 0.792, 95% confidence interval (CI) = 0.638-0.984, P = 0.035]. Subjects with the MTHFR 677CT showed a significantly reduced risk of gastric cancer compared whose with the 677CC genotype (age- and sex-adjusted OR = 0.810; 95% CI = 0.696-0.942, P = 0.006). We also observed no significant interactions between the MTHFR C677T polymorphism and smoking or drinking in the risk of gastric and colorectal cancer.The T allele was found to provide a weak protective association with gastric cancer and colorectal cancer.Although gastric cancer incidence and mortality have been decreasing around the world, it is still the most common cause of cancer death in Korea for both sexes [1]. Colorectal cancer is very common and has increased rapidly along with the westernization of lifestyle in Korea. Although Helicobacter pylori (H. pylori) strains have been proposed to be a major cause of gastric cancer, they do not provide a complete explanation. Epidemio- logical studies have indicated an association between folate intake and a reduced risk of certain cancers [2-5], including gastric cancer [4] and colorectal cancer [3]. Folate deficiencies may result in abnormal DNA methylation and uncontrolled gene expression leading to malignant transformation [6,7].Methylene