雌激素代谢与乳腺癌的发生发展密切相关，4-OHE1(E2)是雌激素致乳腺上皮细胞肿瘤转化的最重要的雌激素代谢物。4-OHE1(E2)主要由细胞色素P450代谢酶CYP1B1代谢生成。CYP1B1具有显著的遗传多态性，可能对4-OHE1(E2)代谢产生直接影响，通过调控雌激素代谢通路从而影响雌激素致乳腺上皮细胞肿瘤转化过程，但目前缺乏相关研究报道。本课题采用体内体外实验探讨CYP1B1遗传多态性对雌激素致乳腺上皮细胞肿瘤转化的影响，首先建立稳定转染CYP1B1各基因型的乳腺上皮MCF-10A细胞模型，探讨CYP1B1遗传多态性对雌激素代谢、活性氧通路、染色体畸变和微卫星不稳定性以及细胞克隆形成的影响，并在裸鼠模型和临床标本中进一步分析验证，研究结果有助于解释雌激素致乳腺癌风险的个体差异性，同时为乳腺癌的临床防治工作提供新的策略和靶点。

Exposure to estrogens has long been recognized as a risk factor for developing breast cancer. 4-OHE1(E2) is the most important estrogen metabolisms that induced neoplastic transformation in mammary epithelial cell. The formation of 4-OHE1(E2) is catalyzed primarily by the CYP1B1. But the effects of the single nucleotide polymorphisms of CYP1B1 on the estrogens metabolism and neoplastic transformation in mammary epithelial cell have not been characterized. In the present study, we will built up mammary epithelial cells MCF-10A which stably transfected with CYP1B1 genetic variants carriers, to explore the effects of CYP1B1 genetic polymorphisms on estrogens metabolism、reactive oxygen species pathway、 chromosome aberrations、microsatellite instability and colony formation. We will also test in nude models and clinical samples in vivo. We hope what we get from the study will help explain the individual differences of breast cancer risk which induced by estrogens and provide new insights for preventing the breast cancer.