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HOME > J Korean Soc Coloproctol > Volume 21(4); 2005 > Article
Original Article
Methylenetetrahydrofolate Reductase C677T and A1298C Polymorphisms in Colorectal Cancer.
Park, Won Cheol , Lee, Jeong Kyun
Journal of the Korean Society of Coloproctology 2005;21(4):241-246

Department of Surgery, College of Medicine, Wonkwang University, Iksan, Korea. rjk@wonkwang.ac.kr
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Abstract

PURPOSE
Recently, the role of vitamins, folate in particular, has been emphasized in the maintenance of health. Folate deficiency is known to give rise to developmental delay, pre-mature vascular disease, neural tube defects, acute leukemia, atherosclerotic vascular disease, delivery defects, breast cancers and gastrointestinal neoplasia. Methylenetetrahydrofolate reductase (MTHFR) is an essential enzyme in folate metabolism, and influences DNA synthesis and DNA methylation. Generally, a low folate level is known to be associated with gastrointestinal neoplasms. Also, the amino- acid-changing and enzyme-activity-reducing nucleotide polymorphism (677C-->T/Ala222Val) has been described in the MTHFR polymorphism and it brings about low enzyme activity, which may reduce DNA methylation and uracil misincorporation into DNA. These processes may be critical for the oncogenic transformation of human cells. Two common single nucleotide polymorphisms (SNPs) resulting in amino-acid changes (677C T/Ala222Val and 1298A C/Glu428Ala) have been described in MTHFR. We investigated the relation between the MTHFR C677T and A1298C polymorphisms derived from colorectal cancers and from controls in the Korean population.
METHODS
One hundred forty-eight (148) individuals with colorectal cancer and 288 healthy persons were analyzed. Blood sampling of each group was performed by using a PCR- RFLP analysis, and MTHFR polymorphism genotypes of 677C/C, 677C/T, 677T/T, 1298AA, 1298AC, and 1298CC were obtained.
RESULTS
The genotype frequencies of MTHFR C677T polymorphisms were 25.0% (CC), 48.0% (CT), 27.0% (TT), and 75.0% (CT+TT), respectively, in case patients and 39.2% (CC), 36.8% (CT), 24.0% (TT), and 60.8% (CT+TT) in controls. The genotype frequencies of MTHFR A1298C polymorphisms were 56.1% (AA), 372% (AC), 6.8% (CC), and 43.9% (AC+CC), respectively, in case patients and 55.6% (AA), 40.3% (AC), 4.2% (CC), and 44.4% (AC+CC) in controls. The 677TT and the 677CT genotypes were associated with significantly increased risks for colorectal cancer (adjusted OR=1.77 and 95% CI=1.02~3.04 in TT; adjusted OR=2.07 and 95% CI=1.28~3.35 in CT) than was the 677CC, genotype but the the 1298CC and 1298 AC genotypes were not associated with significantly increased risks for colorectal cancer (adjusted OR=1.75 and 95% CI= 0.71~4.26 in CC; adjusted OR=0.95 and 95% CI=0.62~1.45 in AC).
CONCLUSIONS
The MTHFR C677T polymorphism may be influenced by colorectal cancer, but the role of the MTHFR A1298C polymorphism needs careful interpretation and confirmation in larger studies.

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