Genotype of human carbonyl reductase CBR3 correlates with doxorubicin disposition and toxicity
Genotype of human carbonyl reductase CBR3 correlates with doxorubicin disposition and toxicity
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DOI：
10.1097/fpc.0b013e328301a869
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发表时间：
2008-07-01
影响因子：
2.6
通讯作者：
Lee, Soo-Chin
中科院分区：
文献类型：
--
作者：
Fan, Lu;Goh, Boon-Cher;Lee, Soo-Chin
多柔比星是一种具有严重骨髓抑制潜力的细胞毒性药物，其变异性很大且难以预测。方法我们将101例接受一线多柔比星治疗的东南亚乳腺癌患者的CBR 1和CBR 3基因型与多柔比星的药代动力学和药效学相关。阿霉素AUC代谢物比值（P=0.009，GG对AA;趋势检验，P=0.004），乳腺肿瘤组织中CBR 3表达较低（P=0.001，GG vs. AA），肿瘤缩小更大（P= 0.015，GG vs. AA），最低点时白细胞和血小板计数降低百分比更大（趋势检验，PA变体比印度人（PA与乳腺肿瘤组织中较高的阿霉素AUC（P=0.009，GG相对于AA）和CBR 3表达相关结论CBR 3基因多态性可解释阿霉素药代动力学和药效学的个体间和种族间差异。药理遗传学和基因组学18：621-629（c）2008年Wolters Kluwer Health垂直栏Lippincott威廉姆斯& Wilkins。
Objectives Doxorubicin is a cytotoxic drug with potential for severe myelosuppression that is highly variable and poorly predictable.Methods We correlated CBR1 and CBR3 genotypes with the pharmacokinetics and pharmacodynamics of doxorubicin in 101 Southeast Asian breast cancer patients receiving first-line doxorubicin.Results A common CBR3 11G > A variant was associated with lower doxorubicinol area under the concentration-time curve (AUC)/doxorubicin AUC metabolite ratio (P=0.009, GG vs. AA; trend test, P=0.004), lower CBR3 expression in breast tumor tissue (P=0.001, GG vs. AA), greater tumor reduction (P= 0.015, GG vs. AA), and greater percentage reduction of leukocyte and platelet counts at nadir (trend test, P A variant than Indians (P A was associated with higher doxorubicinol AUC (P=0.009, GG vs. AA) and CBR3 expression in breast tumor tissue (P=0.001, GG vs AA).Conclusion Polymorphisms in CBR3 may explain interindividual and interethnic variability of doxorubicin pharmacokinetics and pharmacodynamics. Pharmacogenetics and Genomics 18:621-629 (c) 2008 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.