title: Folate-related nutrients, genetic polymorphisms, and colorectal cancer risk: the fukuoka colorectal cancer study.
abstract: One-carbon metabolism plays an important role in colorectal carcinogenesis. Meta-analyses have suggested protective associations of folate and vitamin B6 intakes with colorectal cancer primarily based on studies in Caucasians, and genetic polymorphisms pertaining to the folate metabolism have been a matter of interest. Less investigated are the roles of methionine synthase (MTR) and thymidylate synthetase (TS) polymorphisms in colorectal carcinogenesis. In a study of 816 cases and 815 community controls in Japan, we investigated associations of dietary intakes of folate, methionine, vitamin B2, vitamin B6, and vitamin B12 with colorectal cancer risk. The associations with MTR 2756A>G, MTRR 66A>G, and TSER repeat polymorphism were examined in 685 cases and 778 controls. Methionine and vitamin B12 intakes were inversely associated with colorectal cancer risk, but the associations were totally confounded by dietary calcium and n-3 fatty acids. The other nutrients showed no association with the risk even without adjustment for calcium and n-3 fatty acids. The TSER 2R allele was dose-dependently associated with an increased risk. The MTR and MTRR polymorphisms were unrelated to colorectal cancer risk. There was no measurable gene-gene or gene-nutrient interaction, but increased risk associated with the TSER 2R allele seemed to be confined to individuals with high folate status. This study does not support protective associations for folate and vitamin B6. The TSER 2R allele may confer an increased risk of colorectal cancer. The role of the TSER polymorphism in colorectal carcinogenesis may differ by ethnicity.
authors.affiliation: Department of Preventive Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan E-mail : mmorita@med.kyushu-u.ac.jp.
authors.forename: Makiko
authors.initials: M
authors.lastname: Morita
authors.forename: Guang
authors.initials: G
authors.lastname: Yin
authors.forename: Shin-ichiro
authors.initials: S
authors.lastname: Yoshimitsu
authors.forename: Keizo
authors.initials: K
authors.lastname: Ohnaka
authors.forename: Kengo
authors.initials: K
authors.lastname: Toyomura
authors.forename: Suminori
authors.initials: S
authors.lastname: Kono
authors.forename: Takashi
authors.initials: T
authors.lastname: Ueki
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: Takafumi
authors.initials: T
authors.lastname: Maekawa
authors.forename: Yohichi
authors.initials: Y
authors.lastname: Yasunami
authors.forename: Kenji
authors.initials: K
authors.lastname: Takenaka
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ichimiya
authors.forename: Reiji
authors.initials: R
authors.lastname: Terasaka
mesh_terms: D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000235:genetics; D000328:Adult; D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000453:epidemiology* / Q000235:genetics / Q000378:metabolism; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage*; D005502:Food; D005838:Genotype; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D008715:Methionine / Q000378:metabolism; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012306:Risk; D013940:Thymidylate Synthase / Q000378:metabolism; D014815:Vitamins / Q000008:administration & dosage / Q000378:metabolism; D055815:Young Adult
chemical_list: D014815:Vitamins; D005492:Folic Acid; D008715:Methionine; D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; C585801:MTR protein, human; D013940:Thymidylate Synthase