title: One-carbon metabolism related gene polymorphisms interact with alcohol drinking to influence the risk of colorectal cancer in Japan.
abstract: One-carbon metabolism, in which folate plays an essential role, is involved in DNA methylation and synthesis, and is suspected of impacting on colorectal carcinogenesis. Alcohol is well recognized as a risk factor for colorectal cancer (CRC) and interactions with one-carbon metabolism have also been suggested. Therefore, functional polymorphisms in genes encoding members of this pathway, MTHFR C677T and A1298C (genes for methylenetetrahydrofolate reductase), MTR A2756G (gene for methionine synthase) and TS (gene for thymidylate synthase) tandem repeats polymorphisms, have attracted attention. We conducted a matched case-control study with 257 incident CRC cases and 771 non-cancer controls at the Aichi Cancer Center to clarify associations among folate intake and four polymorphisms with reference to CRC risk. Gene-environment interaction between polymorphisms, drinking and folate consumption was also evaluated. None of the polymorphisms showed any significant impact on CRC risk by genotype alone, but when combined with alcohol consumption the MTHFR 677CC type showed a significantly reduced risk (odds ratio (OR) = 0.45, 95% confidence interval (CI): 0.23-0.86) (P = 0.01). MTR GG showed increased risk only among drinkers (OR = 3.35, 1.40-8.05) (P = 0.047). TS polymorphism did not show statistical significance by genotype alone, while interaction with drinking was significant (P = 0.028). The association was not changed even after stratification by daily folate consumption and drinking habit. In conclusion, we found consistently significant interactions between one-carbon metabolism-related polymorphisms and alcohol drinking.
authors.affiliation: Division of Epidemiology and Prevention, Aichi Cancer Center, Nagoya 464-8681, Japan.
authors.forename: Keitaro
authors.initials: K
authors.lastname: Matsuo
authors.forename: Hidemi
authors.initials: H
authors.lastname: Ito
authors.forename: Kenji
authors.initials: K
authors.lastname: Wakai
authors.forename: Kaoru
authors.initials: K
authors.lastname: Hirose
authors.forename: Toshiko
authors.initials: T
authors.lastname: Saito
authors.forename: Takeshi
authors.initials: T
authors.lastname: Suzuki
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Kato
authors.forename: Takashi
authors.initials: T
authors.lastname: Hirai
authors.forename: Yukihide
authors.initials: Y
authors.lastname: Kanemitsu
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hamajima
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tajima
mesh_terms: D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000235:genetics*; D000368:Aged; D000428:Alcohol Drinking; D002244:Carbon / Q000378:metabolism*; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage; D005838:Genotype; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012307:Risk Factors; D013940:Thymidylate Synthase / Q000235:genetics*
chemical_list: D002244:Carbon; D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; D013940:Thymidylate Synthase