Microsomal epoxide hydrolase variants are not associated with risk of breast cancer.

Introduction Although it has been difficult to establish an epidemiological link between smoking and increased risk for breast cancer, in vitro and in vivo studies have shown that substances present in cigarette smoke could act as breast tissue carcinogens. Polycyclic aromatic hydrocarbons, for instance, cause mammary tumors in rodents, have been shown to be activated by human mammary cells, and can form DNA adducts (1, 2, 3). Carcinogens found in tobacco smoke are metabolized via enzymatic mechanisms involving both activation and detoxification. mEH is a detoxifying enzyme that metabolizes xenobiotic epoxides, including derivatives of polycyclic aromatic hydrocarbons found in cigarette smoke. Genetic polymorphisms within the coding region of the mEPHX gene are known to alter the activity of the enzyme (4). A polymorphism in exon 3 leads to substitution of tyrosine residue 113 to histidine and is associated with reduced enzyme activity. By contrast, a polymorphism in exon 4 leads to substitution of histidine residue 139 to arginine and is associated with enhanced activity. Differences in mEH total activity are more likely to result from variation in protein stability rather than from changes in catalytic activity (5). Polymorphic variation of mEH could modify the risk of breast cancer in women who smoke, because it appears to affect the ability to detoxify tobacco carcinogens. In this study, we examined the association between mEH polymorphisms and breast cancer risk in the presence of cigarette smoking in preand postmenopausal women.