Abstract
BackgroundThis study was designed to investigate an association between the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and the risk of gastric and colorectal cancer in the Korean population.MethodsWe 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.ResultsThe 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.ConclusionsThe T allele was found to provide a weak protective association with gastric cancer and colorectal cancer.
Highlights
This study was designed to investigate an association between the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and the risk of gastric and colorectal cancer in the Korean population
A change of C to T at nucleotide 677 in MTHFR C677T results in an amino acid substance change of an alanine to valine, and this substance is associated with reduced enzyme activity that leads to reduced plasma folate levels [8]
These results suggest that the cancer risk associated with MTHFR polymorphisms may exhibit a gene-nutrient interaction that depends on the level of folate intake or plasma folate levels
Summary
This study was designed to investigate an association between the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and the risk of gastric and colorectal cancer in the Korean population. Colorectal cancer is very common and has increased rapidly along with the westernization of lifestyle in Korea. Epidemio- logical studies have indicated an association between folate intake and a reduced risk of certain cancers [2,3,4,5], including gastric cancer [4] and colorectal cancer [3]. A change of C to T at nucleotide 677 in MTHFR C677T results in an amino acid substance change of an alanine to valine, and this substance is associated with reduced enzyme activity that leads to reduced plasma folate levels [8]. Low enzyme activity of MTHFR C677T variant genotypes are associated with DNA hypomethylation, which may induce genomic instability and thereby affect the expression of oncogenes or tumor suppressor genes
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