Microsomal epoxide hydrolase polymorphisms are not associated with colon cancer risk.

Epidemiologic studies have implicated exposure to tobacco smoke and high intakes of cooked, broiled, or well-done meats in the increased risk of colorectal cancers (1-4). Microsomal epoxide hydrolase (mEH) is a phase II biotransformation enzyme which detoxifies epoxides, including carcinogens such as polycyclic aromatic hydrocarbons found in cigarette smoke and cooked meats (5). A tyrosine to histidine substitution in exon 3 (Y113H) of the mEH gene decreases in vitro enzyme activity by 40%, whereas a histidine to arginine substitution in exon 4 (H139R) increases in vitro enzyme activity by 25% (6). Smaller epidemiologic studies evaluating the relationship between the mEH polymorphisms and risk of colorectal cancer and its precursors have been inconclusive (7-9). We evaluated the risk of colon cancer associated with both the mEH Y113H and H139R genotypes in a large case-control study.