Relationship between CYP3A activity and breast cancer susceptibility in Chinese Han women
Relationship between CYP3A activity and breast cancer susceptibility in Chinese Han women
复制标题
DOI：
10.1007/s00228-003-0649-4
复制
发表时间：
2003-09-01
影响因子：
2.9
通讯作者：
Zhou, HH
中科院分区：
文献类型：
--
作者：
Huang, P;Zhu, B;Zhou, HH
背景乳腺癌是女性最常见的肿瘤类型。乳腺癌的主要原因仍然未知。大量研究表明，内源性类固醇激素，尤其是雌激素，在乳腺癌的发生、发展中起重要作用，雌激素的致癌作用与其主要氧化代谢产物16 α-羟基雌激素和4-羟基雌激素有关。CYP 3A在雌激素的4-和16 α-羟基化中起主要作用。此外，CYP 3A存在于人乳腺上皮细胞中，并且在恶性乳腺细胞中比在邻近的正常乳腺组织中表达更高和更频繁。因此，进一步研究CYP 3A活性与乳腺癌易感性之间的关系具有重要意义。以血浆1-羟基咪达唑仑（1-OHMDZ）/咪达唑仑（MDZ）比值作为CYP 3A活性指标，评价CYP 3A活性与中国汉族女性乳腺癌易感性的关系。129例中国汉族女性乳腺肿瘤患者和121例健康无关女性志愿者入组本研究。禁食过夜后，每例受试者单次口服咪达唑仑（7.5 mg）。在给药后1 h抽取血样（5 ml）。采用高效液相色谱法测定血浆中MDZ及其主要代谢产物1-OH-MDZ的浓度。103例乳腺癌患者和114例对照者的1-OHMDZ与MDZ血浆比值的完整色谱数据可用。1-OHMDZ与MDZ的血浆浓度比在恶性肿瘤患者和对照组中分别为0.4520+/-0.2318和0.3298+/-0.1610。乳腺癌组CYP 3A活性高于对照组（P
Background. 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, 16alpha-hydroxyestrogens and 4-hydroxyestrogens. CYP3A plays a major role in the 4- and 16alpha-hydroxylation 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 susceptibility.Aims. To evaluate the relationship of CYP3A activity to breast cancer susceptibility in Chinese Han women using the plasma 1-hydroxymidazolam (1-OHMDZ) to midazolam (MDZ) ratio as the marker of CYP3A activity.Methods. One hundred and twenty-nine 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 (7.5 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 1-OH-MDZ was measured in all the plasma samples using high-performance liquid chromatography.Results. Complete chromatographic data on plasma ratios of 1-OHMDZ to MDZ for 103 cases of breast cancer and 114 controls were available. The plasma concentration ratios of 1-OHMDZ to MDZ were 0.4520+/-0.2318 and 0.3298+/-0.1610 for the malignant cases and the controls, respectively. A higher CYP3A activity was found in the breast cancer cases than in the controls (P