A Case-control Study on the Relationship between Methylenetetrahydrofolate Reductase C677T, A1298C and G1793A Polymorphism and the Risk of Stomach Cancer

ABSTRACT

PURPOSE: The methylenetetrahydrofolate reductase (MTHFR) play a central role in converting folate to methyl donor for DNA methylation. Genetic variation in folate metabolism are believed to contribute to the risk of acute lymphoblastic leukemia, colon, esophageal and stomach cancer, as well as cardiovascular and cerebrovascular disease. Generally, low folate level is known that it is associated with gastrointestinal neoplasm. Three common single nucleotide polymorphisms (SNPs) resulting in amino-acid changes (C677T/Ala222Val, A1298C/Glu428Ala and G1793A/Arg594Glu) has been described in MTHFR. We studied the relation of MTHFR C677T, A1298C and G1793A polymorphisms derived from stomach cancers and a control group in Korean people. METHODS: We performed a case-control study to examine the relationship between MTHFR C677, A1298C and G1793A polymorphism and the risk of stomach cancer. 124 individuals with stomach cancer and 288 healthy persons were analyzed. Blood sampling of each groups were performed, PCR-RFLP analyzed, as a results, MTHFR polymorphism genotypes of 677C/C, 677C/T, 677T/T, 1298AA, 1298AC, 1298CC, 1793GG, 1793GA and 1793AA were obtained. RESULTS: The genotype frequency of MTHFR C677T polymorphisms were 23.4% (CC), 51.6% (CT), 25.0% (TT), 76.6% (CT+TT) in case patients and 39.2% (CC), 36.8% (CT), 24.0% (TT), 60.8% (CT+TT) in control groups. The genotype frequency of MTHFR A1298C polymorphisms were 38.7% (AA), 54.0% (AC), 7.3% (CC), 61.3% (AC+CC) in case patients and 55.6% (AA), 40.3% (AC), 4.2% (CC), 44.4% (AC+CC) in control groups. The genotype frequency of MTHFR G1793A polymorphisms were 82.3% (GG), 16.9% (GA), 0.8% (AA), 17.7% (GA+AA) in case patients and 85.8% (GG), 11.8% (GA), 2.4% (AA), 14.2% (GA+AA) in control groups. 677TT and 677CT genotype was associated with a significantly increased risk for gastric cancer (adjusted OR=2.15, 95% confidence interval 1.16~3.95 in TT, adjusted OR=2.49, 95% CI 1.47~4.20 in CT) than the 677CC genotype, and 1298CC and 1298 AC genotype also was associated with a significantly increased risk for stomach cancer (adjusted OR=2.87, 95% CI 1.10~|7.49 in CC, adjusted OR= 2.07, 95% CI 1.31~3.26 in AC). But 1793AA and 1793GA genotypes were not association with a significantly increased risk for stomach cancer (adjusted OR=0.29, 95% CI 0.03~|2.47 in AA, adjusted OR=1.55, 95% CI 0.84~2.86 in GA) CONCLUSION: MTHFR C677T and A1298C polymorphism may influence stomach cancer, but MTHFR G1793A polymorphism need careful interpretation and confirmation in larger studies.