Interindividual variation in CYP1A1 expression in breast tissue and the role of genetic polymorphism
Interindividual variation in CYP1A1 expression in breast tissue and the role of genetic polymorphism
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DOI：
10.1093/carcin/21.11.2119
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发表时间：
2000-11-01
期刊：
影响因子：
4.7
通讯作者：
Russell, M
中科院分区：
文献类型：
--
作者：
Goth-Goldstein, R;Stampfer, MR;Russell, M
细胞色素P4501A1 （CYP1A1）酶在转录水平上受到调控，其表达受遗传因素、结构和调控基因多态性以及暴露于多环芳烃（PAHs）等环境因素的影响。为了研究CYP1A1在乳腺癌中的作用，我们研究了CYP1A1在乳腺组织中的表达，从而考虑了所有可能的修饰因素。我们使用新开发的逆转录-聚合酶链反应法测量了来自乳腺癌患者（n = 26）和非癌症个体（n = 32）的58个非肿瘤乳腺组织标本中CYP1A1的表达。CYP1A1在标本之间的表达差异约为400倍，与年龄无关。CYP1A1在乳腺癌患者组织中的表达略高于非癌症患者组织中的表达，但这种差异没有统计学意义。对CYP1A1基因多态性的分析揭示了8个变异，其中7个在无癌组，1个在患者组。变异基因型不能很好地预测表达水平。我们得出结论，CYP1A1高表达可能是乳腺癌的一个危险因素，而已知的CYP1A1多态性并不能很好地预测CYP1A1的表达。
The cytochrome P4501A1 (CYP1A1) enzyme is regulated at the transcriptional level and its expression is influenced by genetic factors, polymorphisms in the structural and regulatory genes, and by environmental factors such as exposure to polycyclic aromatic hydrocarbons (PAHs), To investigate the role of CYP1A1 in breast cancer, we studied CYP1A1 expression in breast tissue, thereby taking all possible modifying factors into account. We measured CYP1A1 expression in 58 non-tumor breast tissue specimens from both breast cancer patients (n = 26) and cancer-free individuals (n = 32) using a newly developed reverse transcription-polymerase chain reaction assay. CYP1A1 expression varied between specimens similar to 400-fold and was independent of age. CYP1A1 expression was somewhat higher in tissue from breast cancer patients than in that from cancer-free individuals, but this difference was not statistically significant. Analysis for CYP1A1 genetic polymorphisms revealed eight variants, seven in the cancer-free group and one in the patient group. The variant genotype was not a good predictor of expression level. We conclude that high CYP1A1 expression could be a risk factor for breast cancer and that the known CYP1A1 polymorphisms are not good predictors of CYP1A1 expression.