Expression of cytochrome P450 1B1 and catechol-O-methyltransferase in breast tissue and their associations with breast cancer risk
Expression of cytochrome P450 1B1 and catechol-O-methyltransferase in breast tissue and their associations with breast cancer risk
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DOI：
10.1158/1055-9965.epi-06-1032
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发表时间：
2007-05-01
影响因子：
3.8
通讯作者：
Zheng, Wei
中科院分区：
文献类型：
--
作者：
Wen, Wanqing;Ren, Zefang;Zheng, Wei
细胞色素P450 1B 1（CYP 1B 1）和儿茶酚-O-甲基转移酶（COMT）是重要的雌激素代谢酶，可能会影响乳腺癌的风险。很少有研究直接测量乳腺组织样本中CYP 1B 1和COMT基因的表达。本研究的受试者是上海乳腺癌研究的参与者亚组，包括64例诊断为乳腺癌的患者和68例诊断为良性乳腺疾病（BBD）的患者，他们为研究提供了肿瘤组织和邻近非肿瘤组织的样本。我们比较了CYP 1B 1和COMT mRNA在乳腺癌患者和BBD患者的肿瘤组织和邻近非肿瘤组织中的表达。邻近非肿瘤组织中CYP 1B 1高水平表达和COMT低水平表达与乳腺癌风险显著增加呈非线性相关。比值比和95%置信区间BBD受试者基因表达水平的第一、第二、第四和第五个五分位数的中点与总体中位数水平相比，（0.07-0.67）、0.81 CYP 1B 1分别为1.69 -0.95、1.20（1.05-1.38）和1.55（1.12-2.15），COMT分别为1.72（1.172.55）、1.19（1.05-1.35）、0.83（0.73-0.95）和0.78（0.65-0.93）。这些结果支持这一假设，即通过增加CYP 1B 1表达和减少COMT表达，儿茶酚雌激素在乳腺组织中的形成和积累可能在乳腺癌风险中发挥重要作用。
Cytochrome P450 1B1 (CYP1B1) and catechol-O-methyltransferase (COMT) are important estrogen-metabolizing enzymes that may affect breast cancer risk. Few studies have directly measured the expression of CYP1B1 and COMT genes in breast tissue samples. The subjects in this study were a subgroup of participants of the Shanghai Breast Cancer Study including 64 patients diagnosed with breast cancer and 68 patients diagnosed with benign breast diseases (BBD) who provided samples of tumor tissue and adjacent nontumor tissue to the study. We compared CYP1B1 and COMT mRNA expression in tumor tissue and adjacent nontumor tissue in both breast cancer patients and BBD patients. High levels of CYP1B1 expression and low levels of COMT expression in adjacent nontumor tissue were associated with a significantly increased breast cancer risk in a nonlinear manner. Odds ratios and 95% confidence intervals (in parentheses) for the midpoints of the first, second, fourth, and fifth quintiles of gene expression levels compared with the overall median levels in BBD subjects were 0.21 (0.07-0.67), 0.81 (0.69-0.95), 1.20 (1.05-1.38), and 1.55 (1.12-2.15) for CYP1B1 and 1.72 (1.172.55), 1.19 (1.05-1.35), 0.83 (0.73-0.95), and 0.78 (0.65-0.93) for COMT, respectively. These results support the hypothesis that the formation and accumulation of catechol estrogens in breast tissue through increased CYP1B1 expression and reduced COMT expression may play a significant role in breast cancer risk.