title: Microsomal epoxide hydrolase polymorphisms, cigarette smoking, and risk of colorectal cancer: the Fukuoka Colorectal Cancer Study.
abstract: Microsomal epoxide hydrolase (EPHX1) plays an important role in the activation and detoxification of polycyclic aromatic hydrocarbons, carcinogens found in cigarette smoke. Polymorphisms in exon 3 (Y113H) and exon 4 (H139R) of the EPHX1 have been associated with enzyme activity. We investigated the risk of colorectal cancer in relation to the EPHX1 Y113H and H139R polymorphisms and assessed effect modifications of cigarette smoking and the other covariates. The interaction between the EPHX1 polymorphisms and selected genetic polymorphisms was also examined. We used data from Fukuoka Colorectal Cancer Study, a community-based case-control study, including 685 cases and 778 controls. In-person interviews were conducted to assess lifestyle factors. The EPHX1 Y113H and H139R polymorphisms were determined by the TaqMan assay and the polymerase chain reaction-restriction fragment length polymorphism, respectively. Neither of the two polymorphisms nor the imputed EPHX1 phenotype was associated with colorectal cancer risk. Cigarette smoking and alcohol intake showed no effect modification on the association with the EPHX1 polymorphisms or the imputed EPHX1 phenotype. Increased risks of colorectal cancer associated with the 113Y allele and imputed EPHX1 phenotype were observed among individuals with high body mass index (BMI; ≥25.0 kg/m(2)), but not among those with low BMI (<25.0 kg/m(2)). The risk decreased with an increasing number of the 139R allele in the null genotypes of GSTM1/GSTT1. It is unlikely that the EPHX1 polymorphisms play an important role in colorectal carcinogenesis. The observed interactions of the EPHX1 polymorphisms with BMI and the GSTM1/GSTT1 genotypes warrant further investigation.
authors.affiliation: Department of Preventive Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Hoirun
authors.initials: H
authors.lastname: Nisa
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Budhathoki
authors.forename: Makiko
authors.initials: M
authors.lastname: Morita
authors.forename: Kengo
authors.initials: K
authors.lastname: Toyomura
authors.forename: Jun
authors.initials: J
authors.lastname: Nagano
authors.forename: Keizo
authors.initials: K
authors.lastname: Ohnaka
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: D000368:Aged; D000483:Alleles; D015992:Body Mass Index; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000209:etiology*; D004851:Epoxide Hydrolases / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D012306:Risk; D012907:Smoking
chemical_list: D004851:Epoxide Hydrolases