title: Gene-environment interactions between alcohol drinking and the MTHFR C677T polymorphism impact on esophageal cancer risk: results of a case-control study in Japan.
abstract: Folate takes part in two biological pathways involved in DNA methylation and synthesis, and a potential protective influence of this nutrient chemical against carcinogenicity has been recognized in several sites, including the esophagus. Therefore, the functional polymorphisms in genes encoding folate metabolizing enzymes, MTHFR C677T and MTR A2756G, might be suspected of impacting on esophageal cancer risk. We therefore conducted a matched case-control study of 165 esophageal cancer cases and 495 non-cancer controls to clarify associations among folate intake, MTHFR C677T and MTR A2756G polymorphisms, and esophageal cancer risk. Gene-environment interactions between the two polymorphisms, and drinking and smoking were also evaluated. Folate consumption and MTHFR 677TT were associated with a non-significant tendency for decreased risk while the MTR genotypes did not show any links in themselves; further, when analysis was limited to heavy drinkers, the MTHFR TT genotype significantly decreased esophageal cancer risk [odds ratio (OR) = 0.27, 95% confidence interval (CI), 0.09-0.76]. The OR for the gene-environment interaction between heavy drinking and the 677TT genotype in the case-only design was 0.31 (95% CI, 0.10-0.94), indicating risk with heavy drinking to be 69% decreased in individuals harboring the 677TT genotype. We failed to find any significant interaction between either of the polymorphisms and smoking.
authors.affiliation: Department of Epidemiology, Huaxi Public Health School, Sichuan University, Chengdu 610041, China.
authors.forename: Chun-Xia
authors.initials: CX
authors.lastname: Yang
authors.forename: Keitaro
authors.initials: K
authors.lastname: Matsuo
authors.forename: Hidemi
authors.initials: H
authors.lastname: Ito
authors.forename: Masayuki
authors.initials: M
authors.lastname: Shinoda
authors.forename: Shunzo
authors.initials: S
authors.lastname: Hatooka
authors.forename: Kaoru
authors.initials: K
authors.lastname: Hirose
authors.forename: Kenji
authors.initials: K
authors.lastname: Wakai
authors.forename: Toshiko
authors.initials: T
authors.lastname: Saito
authors.forename: Takeshi
authors.initials: T
authors.lastname: Suzuki
authors.forename: Takako
authors.initials: T
authors.lastname: Maeda
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tajima
mesh_terms: D000230:Adenocarcinoma / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000428:Alcohol Drinking / Q000009:adverse effects*; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics*; D016022:Case-Control Studies; D004938:Esophageal Neoplasms / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D012307:Risk Factors
chemical_list: D042965:Methylenetetrahydrofolate Reductase (NADPH2)