Epoxide hydrolase Tyr113His polymorphism is associated with elevated risk of colorectal polyps in the presence of smoking and high meat intake

Microsomal epoxide hydrolase (mEH) metabolizes polycyclic aromatic hydrocar bons, carcinogens found in cigarette smoke and cooked meat. Polymorphisms i n 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 st udy. Cases were diagnosed with colonoscopically confirmed adenomas (n = 530 ) or hyperplastic polyps (n = 202); controls (n = 649) were polyp-free at c olonoscopy. Smoking history and meat consumption were obtained from self-ad ministered 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 a denomas and hyperplastic polyps were not statistically different from 1.0. Compared with exon 3 Tyr/Tyr, 0 pack-years, risk was highest among those wi th the exon 3 His/His genotype and > 25 pack-years of smoking [adenoma, odd s ratio (OR) = 4.9 (1.9-12.8); hyperplastic, OR = 7.7 (2.5-24.0)]. Risks we re not elevated among exon 4 homozygous variants, even in the presence of h eavy smoking. Fried, baked, or broiled meat intake of greater than or equal to two servings/week (high) compared with less than or equal to one servin g/week was associated with a 2-fold increase in risk of adenoma. The highes t risks were seen for those with the exon 3 His/His genotype and high cooke d meat intake [OR = 3.3 (1.4-7.9); reference group: Tyr/Tyr, less than or e qual to1 serving/week). Although mEH polymorphisms are not associated with an increased risk of col orectal polyps overall, genotypes that produce a slow phenotype appear to b e associated with an increased risk in the presence of smoking and high int akes of cooked meat.