title: Epoxide hydrolase Tyr113His polymorphism is associated with elevated risk of colorectal polyps in the presence of smoking and high meat intake.
abstract: Microsomal epoxide hydrolase (mEH) metabolizes polycyclic aromatic hydrocarbons, carcinogens found in cigarette smoke and cooked meat. Polymorphisms in exon 3 and exon 4 of the mEH gene have been found to alter mEH activity. We investigated the association between these polymorphisms and colorectal polyps within the Minnesota Cancer Prevention Research Unit case-control study. Cases were diagnosed with colonoscopically confirmed adenomas (n = 530) or hyperplastic polyps (n = 202); controls (n = 649) were polyp-free at colonoscopy. Smoking history and meat consumption were obtained from self-administered questionnaires before colonoscopy. mEH genotypes were determined by PCR/RFLP or oligonucleotide ligation assay. The overall risks associated with exon 3 or exon 4 polymorphisms for both adenomas and hyperplastic polyps were not statistically different from 1.0. Compared with exon 3 Tyr/Tyr, 0 pack-years, risk was highest among those with the exon 3 His/His genotype and >25 pack-years of smoking [adenoma, odds ratio (OR) = 4.9 (1.9-12.8); hyperplastic, OR = 7.7 (2.5-24.0)]. Risks were not elevated among exon 4 homozygous variants, even in the presence of heavy smoking. Fried, baked, or broiled meat intake of > or =two servings/week (high) compared with < or =one serving/week was associated with a 2-fold increase in risk of adenoma. The highest risks were seen for those with the exon 3 His/His genotype and high cooked meat intake [OR = 3.3 (1.4-7.9); reference group: Tyr/Tyr, < or = 1 serving/week). Although mEH polymorphisms are not associated with an increased risk of colorectal polyps overall, genotypes that produce a slow phenotype appear to be associated with an increased risk in the presence of smoking and high intakes of cooked meat.
authors.affiliation: Fred Hutchinson Cancer Research Center, Cancer Prevention Research Program, Seattle, Washington 98109-1024, USA. nulrich@fhcrc.org
authors.forename: C M
authors.initials: CM
authors.lastname: Ulrich
authors.forename: J
authors.initials: J
authors.lastname: Bigler
authors.forename: J A
authors.initials: JA
authors.lastname: Whitton
authors.forename: R
authors.initials: R
authors.lastname: Bostick
authors.forename: L
authors.initials: L
authors.lastname: Fosdick
authors.forename: J D
authors.initials: JD
authors.lastname: Potter
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D003111:Colonic Polyps / Q000209:etiology / Q000235:genetics*; D003296:Cooking; D004032:Diet; D004851:Epoxide Hydrolases / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005838:Genotype; D006632:Histamine / Q000235:genetics; D006801:Humans; D008297:Male; D008460:Meat; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*; D014443:Tyrosine / Q000235:genetics
chemical_list: D014443:Tyrosine; D006632:Histamine; D004851:Epoxide Hydrolases