Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China.
Maturitas. 2012 Jun;72(2):139-45. doi: 10.1016/j.maturitas.2012.03.003. Epub 2012 Mar 31.
To investigate the expression levels of genes encoding phase I and phase II estradiol-metabolizing enzymes, and their association with breast cancer risk in Chinese women.
The mRNA expression levels of cytochrome P450 (CYP) 1A1, 1B1 and 3A4 and catechol-O-methyltransferase (COMT) were examined in the breast tumor tissues, matched adjacent non-tumor tissues and the tissues with benign breast disease (BBD) by fluorescent quantitative real-time PCR.
Compared to BBD tissue, the mRNA expression of CYP1A1, CYP1B1 and CYP3A4 significantly reduced by 81.8%, 77.5%, and 85.6%, respectively, in the breast tumor tissue and by 27.2%, 38.8%, and 51.3%, respectively, in the adjacent non-tumor tissue in average (p<0.0001). COMT mRNA was 6.9 and 6.4 fold higher in the breast tumor and match non-tumor tissue (p<0.0001) than in the BBD, respectively. The level of COMT detected in pre-menopausal group and lymph nodal stage N1-N2 group was lower than that in post-menopausal group (p=0.0292) and N0 group (p=0.0389), respectively.
Significantly deceased expression of estradiol-metabolizing enzymes might result in the excess exposure of intratumoural E2, which could be one of the important risk factors for breast cancer. Significantly elevated COMT expression suggested that COMT could play a key role in breast tumor formation.
研究编码 I 相和 II 相雌二醇代谢酶的基因表达水平及其与中国女性乳腺癌风险的关系。
采用荧光定量实时 PCR 方法检测乳腺癌组织、配对非肿瘤组织和良性乳腺疾病（BBD）组织中细胞色素 P450（CYP）1A1、1B1 和 3A4 及儿茶酚-O-甲基转移酶（COMT）的 mRNA 表达水平。
与 BBD 组织相比，乳腺癌组织中 CYP1A1、CYP1B1 和 CYP3A4 的 mRNA 表达水平分别平均降低了 81.8%、77.5%和 85.6%，相邻非肿瘤组织中分别降低了 27.2%、38.8%和 51.3%（p<0.0001）。COMT mRNA 在乳腺癌和匹配的非肿瘤组织中的表达分别比 BBD 组织高 6.9 和 6.4 倍（p<0.0001）。COMT 水平在绝经前组和淋巴结分期 N1-N2 组中低于绝经后组（p=0.0292）和 N0 组（p=0.0389）。
雌二醇代谢酶的表达显著降低可能导致肿瘤内 E2 的过度暴露，这可能是乳腺癌的一个重要危险因素。COMT 表达显著升高提示 COMT 可能在乳腺癌形成中起关键作用。
