title: Methylenetetrahydrofolate reductase C677T and A1298C polymorphisms and colorectal cancer: the Fukuoka Colorectal Cancer Study.
abstract: Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme regulating folate metabolism, which affects DNA synthesis and methylation. This study investigated the relation of MTHFR C677T and A1298C polymorphisms to colorectal cancer in a case-control study in Fukuoka, Japan. The subjects comprised 685 incident cases of histologically confirmed colorectal adenocarcinomas and 778 community controls selected randomly in the study area. The genotype was determined by the PCR-RFLP method using genomic DNA extracted from buffy coat. Alcohol use was ascertained by in-person interview. Statistical adjustment was made for gender, age class, area, and alcohol use. The MTHFR 677TT genotype was associated with a statistically significant decrease in the risk with an adjusted odds ratio of 0.69 (95% confidence interval 0.51-0.93) compared with the 677CC and 677CT combined, and the decrease was most evident in individuals with no alcohol consumption. While the A1298C polymorphism showed no measurable association with the overall risk of colorectal cancer, the 1298CC genotype was associated with a statistically significant increase in the risk when alcohol consumption was high, and was also associated with an approximately 2-fold increase in the risk of each of proximal and distal colon cancer. The findings add to evidence that individuals with the MTHFR 677TT genotype have a decreased risk of colorectal cancer in the absence of folate depletion, suggesting a protective role of folate by ensuring a sufficient thymidylate pool for DNA synthesis. Because very few individuals had the 1298CC genotype, the findings regarding the A1298C polymorphism need careful interpretation and confirmation in larger studies.
authors.affiliation: Department of Preventive Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582.
authors.forename: Guang
authors.initials: G
authors.lastname: Yin
authors.forename: Suminori
authors.initials: S
authors.lastname: Kono
authors.forename: Kengo
authors.initials: K
authors.lastname: Toyomura
authors.forename: Tomoko
authors.initials: T
authors.lastname: Hagiwara
authors.forename: Jun
authors.initials: J
authors.lastname: Nagano
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Mizoue
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Mibu
authors.forename: Masao
authors.initials: M
authors.lastname: Tanaka
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kakeji
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Maehara
authors.forename: Takeshi
authors.initials: T
authors.lastname: Okamura
authors.forename: Koji
authors.initials: K
authors.lastname: Ikejiri
authors.forename: Kitaroh
authors.initials: K
authors.lastname: Futami
authors.forename: Yohichi
authors.initials: Y
authors.lastname: Yasunami
authors.forename: Takafumi
authors.initials: T
authors.lastname: Maekawa
authors.forename: Kenji
authors.initials: K
authors.lastname: Takenaka
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ichimiya
authors.forename: Nobutoshi
authors.initials: N
authors.lastname: Imaizumi
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology / Q000235:genetics*; D000328:Adult; D000368:Aged; D000428:Alcohol Drinking; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007564:Japan; D008019:Life Style; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012307:Risk Factors
chemical_list: D042965:Methylenetetrahydrofolate Reductase (NADPH2)