MICROSOMAL EPOXIDE HYDROLASE POLYMORPHISM AS A RISK FACTOR FOR OVARIAN-CANCER

Microsomal epoxide hydrolase (EPHX) is one of many enzymes involved in the metabolism of endogenous and exogenous toxicants. Polymorphic for ms of the human EPHX gene have been described that vary in enzymatic a ctivity, and one, Tyr113His, has been associated with hepatocellular c arcinoma susceptibility. We demonstrated that EPHX was highly expresse d in the human ovary, and investigated whether specific EPHX genotypes are associated with ovarian cancer susceptibility. Seventy-three Cauc asian patients with ovarian cancer and 75 Caucasian-female controls wi thout cancer were genotyped for the Tyr113His polymorphism by a polyme rase chain reaction-restriction fragment length polymorphism assay. Th e frequency of the homozygous high-activity genotype was 41% in the co ntrol population and 64% in the ovarian cancer patients. The odds rati o for ovarian cancer with this genotype was 2.6 (95% confidence interv al 1.3, 5.0; P < 0.01). The increased ovarian cancer risk associated w ith the high-activity genotype could reflect differences in metabolic activation of endogenous or exogenous carcinogens. (C) 1996 Wiley-Liss , Inc.