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人类细胞色素P450 1B1的药物遗传学与调控:对激素介导的肿瘤代谢的影响及治疗干预的新靶点

Pharmacogenetics and regulation of human cytochrome P450 1B1: implications in hormone-mediated tumor metabolism and a novel target for therapeutic intervention.

作者信息

Sissung Tristan M, Price Douglas K, Sparreboom Alex, Figg William D

机构信息

Clinical Pharmacology Research Core, National Cancer Institute, 9000 Rockville Pike, Building 10, Room 5A01, Bethesda, MD 20892, USA.

出版信息

Mol Cancer Res. 2006 Mar;4(3):135-50. doi: 10.1158/1541-7786.MCR-05-0101.

Abstract

Several of the hormone-mediated cancers (breast, endometrial, ovarian, and prostate) represent major cancers in both incidence and mortality rates. The etiology of these cancers is in large part modulated by the hormones estrogen and testosterone. As advanced disease develops, the common treatment for these cancers is chemotherapy. Thus, genes that can alter tissue response to hormones and alter clinical response to chemotherapy are of major interest. The cytochrome P450 1B1 (CYP1B1) may be involved in disease progression and modulate the treatment in the above hormone-mediated cancers. This review will focus on the pharmacogenetics of CYP1B1 in relation to hormone-mediated cancers and provide an assessment of cancer risk based on CYP1B1 polymorphisms and expression. In addition, it will provide a summary of CYP1B1 gene regulation and expression in normal and neoplastic tissue.

摘要

几种激素介导的癌症(乳腺癌、子宫内膜癌、卵巢癌和前列腺癌)在发病率和死亡率方面都是主要癌症。这些癌症的病因在很大程度上受雌激素和睾酮调节。随着晚期疾病的发展,这些癌症的常见治疗方法是化疗。因此,能够改变组织对激素的反应并改变对化疗的临床反应的基因备受关注。细胞色素P450 1B1(CYP1B1)可能参与上述激素介导癌症的疾病进展并调节治疗。本综述将聚焦于CYP1B1与激素介导癌症相关的药物遗传学,并基于CYP1B1多态性和表达评估癌症风险。此外,还将总结CYP1B1基因在正常组织和肿瘤组织中的调控与表达。

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