PURPOSE: Methylenetetrahydrofolate reductase (MTHFR) is a critical enzyme regulating folate level, which affects DNA synthesis and methylation. MTHFR is highly polymorphic, and its variant genotypes result in decreased MTHFR enzyme activity and lower plasma folate level. Generally, a low folate level is known to be associated with a gastrointestinal neoplasm. Three common single nucleotide polymorphisms (SNPs) resulting in amino-acid changes (C677T, A1298C and G1793A) have been reported in MTHFR. We studied the relationship of MTHFR C677T, A1298C and G1793A polymorphisms between from colon cancer group and control group of Korean people. METHODS: We performed a case- control study to examine the relationship between MTHFR C677, A1298C, and G1793A polymorphisms and the risk of colon cancer. Two hundred seven (207) individuals with colon cancer and 288 healthy persons were analyzed. Blood sampling of each group was performed, and (PCR-RFLP) was analyzed; as a result, MTHFR polymorphism genotypes were obtained. RESULTS: The genotype frequencies of MTHFR C677T polymorphisms were 27.1% (CC), 48.3% (CT), 24.6% (TT), and 72.9% (CT+TT) in the patient group and 39.2% (CC), 36.8% (CT), 24.0% (TT), and 60.8% (CT+TT) in the control group. The genotype frequencies of MTHFR A1298C polymorphisms were 58% (AA), 35.7% (AC), 6.3% (CC), and 42% (AC+CC) in the patient group and 55.6% (AA), 40.3% (AC), 4.2% (CC), and 44.4% (AC+CC) in control group. The genotype frequencies of MTHFR G1793A polymorphisms were 83% (GG), 15.9% (GA), 1% (AA), and 16.9% (GA+AA) in the patient group and 85.8% (GG), 11.8% (GA), 2.4% (AA), and 14.2% (GA+AA) in the control group. The 677CT genotype was associated with a significantly increased risk for colon cancer (adjusted OR=1.90, 95% confidence interval: 1.25~2.90 in CT) than the 677CC genotype. The 1298CC, 1298AC, 1793AA, and 1793GA genotypes were not associated with a significantly increased risk for colon cancer. CONCLUSIONS: The MTHFR C677T polymorphism may influence colon cancer, but the MTHFR A1298C and G1793A polymorphisms need to be studied further for careful interpretation and confirmation in larger studies.