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Microsomal epoxide hydrolase polymorphisms, cigarette smoking, and risk of colorectal cancer: The Fukuoka Colorectal Cancer Study
Author(s) -
Nisa Hoirun,
Budhathoki Sanjeev,
Morita Makiko,
Toyomura Kengo,
Nagano Jun,
Ohnaka Keizo,
Kono Suminori,
Ueki Takashi,
Tanaka Masao,
Kakeji Yoshihiro,
Maehara Yoshihiko,
Okamura Takeshi,
Ikejiri Koji,
Futami Kitaroh,
Maekawa Takafumi,
Yasunami Yohichi,
Takenaka Kenji,
Ichimiya Hitoshi,
Terasaka Reiji
Publication year - 2013
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.21897
Subject(s) - microsomal epoxide hydrolase , colorectal cancer , biology , medicine , carcinogen , genotype , oncology , genetics , cancer , epoxide hydrolase , gene , microsome , in vitro
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. © 2012 Wiley Periodicals, Inc.