CYTOCHROME P450 PHARMACOGENETICS AS A PREDICTOR OF TOXICITY AND CLINICAL EFFICAC

细胞色素 P450 药物遗传学作为毒性和临床疗效的预测因子

• 批准号: 7717528
• 负责人: Bryan Paul Schneider
• 金额: $ 0.02万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-12-01 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7717528
• 关键词: Age; Anthracycline Antibiotics; Anthracyclines; Cardiac; Clinical; Cohort Studies; Computer Retrieval of Information on Scientific Projects Database; Cyclophosphamide; Cytochrome P450; Dose; Doxorubicin; Enzymes; Excretory function; Fertility; Functional disorder; Funding; Genetic Polymorphism; Genetic Variation; Genotype; Goals; Grant; Hot flushes; Institution; Invasive; Lupus Nephritis; Menopausal hot flushes; Metabolism; Nausea and Vomiting; Patients; Pharmaceutical Preparations; Pharmacogenetics; Premature Menopause; Premature Ovarian Failure; Premenopause; Reproduction; Research; Research Personnel; Resources; Role; Secondary to; Social Impacts; Source; Standards of Weights and Measures; Thrombocytopenia; Toxic effect; United States National Institutes of Health; Woman; bone; cohort; cytotoxic; hormone therapy; malignant breast neoplasm; reproductive

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The combination of an anthracycline and cyclophosphamide with or without additional cytotoxic or hormonal therapy represents a common standard approach to therapy in women with invasive breast cancer. Unfortunately, not all women enjoy long term survival with this approach and toxicity is common. A particular concern among women of reproductive age is the permanent loss of fertility secondary to therapy. In addition to the psycho-social impact of premature menopause with regard to reproduction, other associated negative sequelae include hot flashes and possible adverse bone-related consequences. The specific toxicities of doxorubicin include nausea and vomiting, mylosuppression, thrombocytopenia, and cardiac dysfunction (dose-related). While multiple factors influence both the efficacy and the toxicity of therapy, one important variable is the ability of the host to metabolize and clear a compound. Thus, in addition to the agent selected and the total dose administered, polymorphisms of the cytochrome P450 (CYP450) enzymes that alter the metabolism and excretion of chemotherapeutic drugs may have an impact on efficacy and toxicity. A prior retrospective, cohort study identified selected CYP450 enzyme genotypes which predicted for premature ovarian failure in lupus nephritis patients treated with single agent cyclophosphamide. The goal of this study is to delineate the role of genetic variations in premature menopause, hot flashes, and other toxicities in a cohort of premenopausal women with early breast cancer.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 在有或不使用其他细胞毒性或荷尔蒙治疗的蒽环类和环磷酰胺的组合中，是侵入性乳腺癌女性的常见标准治疗方法。 不幸的是，并非所有女性都以这种方法享有长期生存，而毒性很普遍。 生殖年龄的妇女特别关注的是继发于治疗的永久性丧失。 除了更年期对繁殖的心理社会影响外，其他相关的负后遗症还包括热闪光和可能的不良骨相关后果。 阿霉素的特异性毒性包括恶心和呕吐，甲状腺抑制，血小板减少症和心脏功能障碍（与剂量相关）。 尽管多个因素都会影响治疗的疗效和毒性，但一个重要的变量是宿主代谢和清除化合物的能力。 因此，除了选定的药物和总剂量外，细胞色素P450（CYP450）的多态性改变了化学治疗药物的代谢和排泄可能会影响疗效和毒性。一项先前的回顾性队列研究确定了选定的CYP450酶基因型，这些酶基因型预测了用单药环磷酰胺治疗的狼疮性肾炎患者的卵巢过早衰竭。 这项研究的目的是描述遗传变异在更年期，热闪光和其他毒性中的作用，并在患有早期乳腺癌的绝经前女性中。