Authors: Ping Huang Bing Zhu LianSheng Wang DongSheng Ouyang SongLin Huang XiaoPing Chen HongHao Zhou
Publish Date: 2003/08/22
Volume: 59, Issue: 5-6, Pages: 471-476
Abstract
Breast cancer is the most frequent type of tumor in women The main cause of breast cancer remains unknown Extensive studies have shown that endogenous steroid hormones especially estrogens are important in the development and the progression of breast cancer and the carcinogenesis of estrogens is related to their major oxidative metabolites 16αhydroxyestrogens and 4hydroxyestrogens CYP3A plays a major role in the 4 and 16αhydroxylation of estrogens Furthermore CYP3A is present in human mammary epithelial cells and expressed higher and more frequently in malignant breast cells than in the adjacent normal breast tissue Hence it will be significant to perform more work to determine the association between CYP3A activity and breast cancer susceptibilityOne hundred and twentynine Chinese Han female breast tumor patients and 121 healthy unrelated female volunteers were enrolled in the current study After an overnight fast each subject was administered a single oral dose 75 mg of midazolam Blood samples 5 ml were drawn at 1 h after the drug administration The concentration of parent MDZ and its major metabolite 1OHMDZ was measured in all the plasma samples using highperformance liquid chromatographyComplete chromatographic data on plasma ratios of 1OHMDZ to MDZ for 103 cases of breast cancer and 114 controls were available The plasma concentration ratios of 1OHMDZ to MDZ were 04520±02318 and 03298±01610 for the malignant cases and the controls respectively A higher CYP3A activity was found in the breast cancer cases than in the controls P0001 and the CYP3A activity of patients with lymphnode metastasis was higher than that of patients without lymphnode metastasis P=0028 CYP3A activity in estrogen receptor or progesterone receptor positive cases was the same as in estrogen receptor or progesterone receptor negative cases P=0124 0175We thank the staff at the Department of Surgery in the Tumor Hospital of Hunan Province for the collection of all breast cancer samples This project was supported by China Medical Board grants 99–697 and 01–755 and National Natural Science Foundation of China grant F30130210
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