Lancaster J M, Brownlee H A, Bell D A, Futreal P A, Marks J R, Berchuck A, Wiseman R W, Taylor J A
National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA.
Mol Carcinog. 1996 Nov;17(3):160-2. doi: 10.1002/(SICI)1098-2744(199611)17:3<160::AID-MC8>3.0.CO;2-J.
Microsomal epoxide hydrolase (EPHX) is one of many enzymes involved in the metabolism of endogenous and exogenous toxicants. Polymorphic forms of the human EPHX gene have been described that vary in enzymatic activity, and one, Tyr113His, has been associated with hepatocellular carcinoma susceptibility. We demonstrated that EPHX was highly expressed in the human ovary, and investigated whether specific EPHX genotypes are associated with ovarian cancer susceptibility. Seventy-three Caucasian patients with ovarian cancer and 75 Caucasian-female controls without cancer were genotyped for the Tyr113His polymorphism by a polymerase chain reaction-restriction fragment length polymorphism assay. The frequency of the homozygous high-activity genotype was 41% in the control population and 64% in the ovarian cancer patients. The odds ratio for ovarian cancer with this genotype was 2.6 (95% confidence interval 1.3, 5.0; P < 0.01). The increased ovarian cancer risk associated with the high-activity genotype could reflect differences in metabolic activation of endogenous or exogenous carcinogens.
微粒体环氧化物水解酶（EPHX）是参与内源性和外源性毒物代谢的众多酶之一。已描述了人类EPHX基因的多态性形式，其酶活性各不相同，其中一种Tyr113His与肝细胞癌易感性相关。我们证明EPHX在人卵巢中高度表达，并研究了特定的EPHX基因型是否与卵巢癌易感性相关。通过聚合酶链反应-限制性片段长度多态性分析，对73例患有卵巢癌的白种人患者和75例无癌症的白种人女性对照进行了Tyr113His多态性基因分型。纯合高活性基因型在对照人群中的频率为41%，在卵巢癌患者中为64%。具有该基因型的卵巢癌的优势比为2.6（95%置信区间1.3,5.0；P<0.01）。与高活性基因型相关的卵巢癌风险增加可能反映了内源性或外源性致癌物代谢激活的差异。
