Microsomal epoxide hydrolase polymorphisms, cigarette smoking, and risk of colorectal cancer: The Fukuoka colorectal cancer study

Hoirun Nisa, Sanjeev Budhathoki, Makiko Morita, Kengo Toyomura, Jun Nagano, Keizo Ohnaka, Suminori Kono, Takashi Ueki, Masao Tanaka, Yoshihiro Kakeji, Yoshihiko Maehara, Takeshi Okamura, Koji Ikejiri, Kitaroh Futami, Takafumi Maekawa, Yohichi Yasunami, Kenji Takenaka, Hitoshi Ichimiya, Reiji Terasaka

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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; ≥25.0kg/m2), but not among those with low BMI (<25.0kg/m2). 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.

Original languageEnglish
Pages (from-to)619-626
Number of pages8
JournalMolecular Carcinogenesis
Volume52
Issue number8
DOIs
Publication statusPublished - Aug 1 2013

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Epoxide Hydrolases
Colorectal Neoplasms
Smoking
Phenotype
Exons
Alleles
Genotype
Polycyclic Aromatic Hydrocarbons
Genetic Polymorphisms
Smoke
Tobacco Products
Restriction Fragment Length Polymorphisms
Carcinogens
Case-Control Studies
Life Style
Carcinogenesis
Body Mass Index
Alcohols
Interviews
Polymerase Chain Reaction

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cancer Research

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Microsomal epoxide hydrolase polymorphisms, cigarette smoking, and risk of colorectal cancer : The Fukuoka colorectal cancer study. / 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.

In: Molecular Carcinogenesis, Vol. 52, No. 8, 01.08.2013, p. 619-626.

Research output: Contribution to journalArticle

Nisa, H, Budhathoki, S, Morita, M, Toyomura, K, Nagano, J, Ohnaka, K, Kono, S, Ueki, T, Tanaka, M, Kakeji, Y, Maehara, Y, Okamura, T, Ikejiri, K, Futami, K, Maekawa, T, Yasunami, Y, Takenaka, K, Ichimiya, H & Terasaka, R 2013, 'Microsomal epoxide hydrolase polymorphisms, cigarette smoking, and risk of colorectal cancer: The Fukuoka colorectal cancer study', Molecular Carcinogenesis, vol. 52, no. 8, pp. 619-626. https://doi.org/10.1002/mc.21897
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. / Microsomal epoxide hydrolase polymorphisms, cigarette smoking, and risk of colorectal cancer : The Fukuoka colorectal cancer study. In: Molecular Carcinogenesis. 2013 ; Vol. 52, No. 8. pp. 619-626.
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AU - Nagano, Jun

AU - Ohnaka, Keizo

AU - Kono, Suminori

AU - Ueki, Takashi

AU - Tanaka, Masao

AU - Kakeji, Yoshihiro

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AU - Futami, Kitaroh

AU - Maekawa, Takafumi

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