Epoxide hydrolases (EHs) are biotransformation enzymes that catalyze the hydrolysis of arene and aliphatic epoxides to less reactive and more water soluble dihydrodiols by the trans addition of water. The enzymatic hydration is essentially irreversible and produces mainly metabolites of lower reactivity that can be conjugated and excreted, and, therefore, are generally regarded as detoxifying. Microsomal EH (mEH) is one of many enzymes involved in the metabolism of endogenous levels of and exogenous toxicants such as tobacco-derived carcinogens. mEH exhibits a broad substrate specificity, while the soluble EH (sEH) is an enzyme with a "complementary" substrate specificity to mEH. The mEH protein is encoded by the EPHX1 gene, which maps to chromosome 1q42.12. Polymorphism of the EPHX1 gene is a risk factor ovarian cancer and hepatocellular carcinoma.