Lessons for pharmacogenomics studies: association study between CYP2D6 genotype and tamoxifen response
Lessons for pharmacogenomics studies: association study between CYP2D6 genotype and tamoxifen response
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DOI：
10.1097/fpc.0b013e32833af231
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发表时间：
2010-09-01
影响因子：
2.6
通讯作者：
Zembutsu, Hitoshi
中科院分区：
文献类型：
--
作者：
Kiyotani, Kazuma;Mushiroda, Taisei;Zembutsu, Hitoshi
我们之前报道了 282 名接受他莫昔芬单药治疗的日本乳腺癌患者的细胞色素 P450 2D6 (CYP2D6) 基因型与临床结果之间存在显着相关性。尽管许多研究小组提供的证据表明 CYP2D6 基因型是他莫昔芬反应最强的预测因子之一，但结果仍然存在争议。我们假设伴随治疗是这些有争议结果的原因之一。然后，我们研究了 167 名接受他莫昔芬联合治疗的乳腺癌患者，以评估联合治疗对关联分析的影响，并观察到 CYP2D6 基因型与无复发生存率之间没有显着关联（P = 0.44，风险比：0.64，95% 置信区间：0.20-1.99，有两个变异等位基因的患者与没有变异等位基因的患者相比）。当我们对淋巴结状态和肿瘤大小进行两个亚组分析时，我们观察到仅在接受他莫昔芬单药治疗的患者中，CYP2D6 基因型与临床结果之间呈正相关。这项研究解释了报告结果之间的部分差异。药物遗传学和基因组学 20: 565-568 (C) 2010 Wolters Kluwer Health |利平科特·威廉姆斯和威尔金斯。
We earlier reported a significant association between the cytochrome P450 2D6 (CYP2D6) genotype and the clinical outcome in 282 Japanese breast cancer patients receiving tamoxifen monotherapy. Although many research groups have provided evidence indicating the CYP2D6 genotype as one of the strongest predictors of tamoxifen response, the results still remain controversial. We hypothesized that concomitant treatment was one of the causes of these controversial results. We then studied 167 breast cancer patients who received tamoxifen-combined therapy to evaluate the effects of concomitant treatment on the association analysis and observed no significant association between CYP2D6 genotype and recurrence-free survival (P = 0.44, hazard ratio: 0.64, 95% confidential interval: 0.20-1.99 in patients with two variant alleles vs. patients without a variant allele). When we carried out two subgroup analyses for nodal status and tumor size, we observed a positive association between the CYP2D6 genotype and the clinical outcome only in patients who received tamoxifen monotherapy. This study explained a part of the discrepancies among the reported results. Pharmacogenetics and Genomics 20: 565-568 (C) 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.