CYP3A5基因变异,CYP2D6、SULT1A1 UGT2B15和三苯氧胺反应在绝经后的乳腺癌患者。

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维根曼P, Elingarami年代,Carstensen J,“斯太尔O, Nordenskjold B, Wingren年代

CYP3A5基因变异,CYP2D6、SULT1A1 UGT2B15和三苯氧胺反应在绝经后的乳腺癌患者。

乳腺癌研究》2007;9 (1):R7。

PubMed ID

17244352 (在PubMed

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简介:他莫昔芬治疗可以减少复发的风险,延长乳腺癌患者阳性雌激素受体的生存。即使大多数病人受益于它莫西芬,许多乳腺肿瘤反应失败或产生耐药性。因为他莫昔芬是广泛代谢酶多态,提出的一种机制抵抗是改变新陈代谢。在目前的研究中我们调查的预后和/或预测价值功能多态性在细胞色素P450 3 a5 CYP3A5 (* 3), CYP2D6 (* 4), sulphotransferase 1 a1 (SULT1A1;2 * 2)和UDP-glucuronosyltransferase去往b15 (UGT2B15;乳腺癌患者服用它莫西芬* 2)。方法:在所有,服用它莫西芬677年绝经后的乳腺癌患者,其中238人随机2或5年他莫昔芬,被用聚合酶链反应限制性片段长度多态性基因分型或PCR与变性高效液相色谱法。结果:预后评估在总人口中执行显示更好的患者无病生存纯合子CYP2D6 * 4。CYP3A5 SULT1A1和UGT2B15没有观察到的预后意义。随机组中我们发现,CYP3A5 * 3等位基因的纯合子的运营商有复发的风险增加,当与他莫昔芬治疗2年,虽然这不是统计学意义(风险比(人力资源)= 2.84,95%可信区间(CI) = 0.68 ~ 11.99, P = 0.15)。 In the group randomised to 5 years' tamoxifen the survival pattern shifted towards a significantly improved recurrence-free survival (RFS) among CYP3A5*3-homozygous patients (HR = 0.20, 95% CI = 0.07 to 0.55, P = 0.002). No reliable differences could be seen between treatment duration and the genotypes of CYP2D6, SULT1A1 or UGT2B15. The significantly improved RFS with prolonged tamoxifen treatment in CYP3A5*3 homozygotes was also seen in a multivariate Cox model (HR = 0.13, CI = 0.02 to 0.86, P = 0.03), whereas no differences could be seen for CYP2D6, SULT1A1 and UGT2B15. CONCLUSION: The metabolism of tamoxifen is complex and the mechanisms responsible for the resistance are unlikely to be explained by a single polymorphism; instead it is a combination of several mechanisms. However, the present data suggest that genetic variation in CYP3A5 may predict response to tamoxifen therapy.

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药物酶

药物	酶	类	生物	药理作用	行动
它莫西芬	Sulfotransferase 1 a1	蛋白质	人类	未知的	底物	细节