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Epoxide Hydrolase Tyr113His Polymorphism Is Associated with Elevated Risk of Colorectal Polyps in the Presence of Smoking and High Meat Intake

Fred Hutchinson Cancer Research Center, Cancer Prevention Research Program, Seattle, Washington 98109-1024 [C. M. U, J. B., J. A. W., J. D. P.]; Department of Epidemiology, University of Washington, Seattle, Washington 98195 [C. M. U., J. D. P.]; South Carolina Cancer Center, University of South Carolina, Columbia, South Carolina 29203 [R. B.]; and University of Minnesota, CPCRA Statistical Center, Minneapolis, Minnesota 55454 [L. F.]

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 two servings/week (high) compared with 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, 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.

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