通过体外药物反应和多变量全基因组关联评估混合在癌症治疗中的作用。
Evaluating the role of admixture in cancer therapy via in vitro drug response and multivariate genome-wide associations.
作者信息
Jack John, Havener Tammy M, McLeod Howard L, Motsinger-Reif Alison A, Foster Matthew
机构信息
Department of Statistics, North Carolina State University, 2601 Stinson Drive, Raleigh, NC 27695, USA.
Bioinformatics Research Center, North Carolina State University, 2601 Stinson Drive, Raleigh, NC 27695, USA.
出版信息
Pharmacogenomics. 2015;16(13):1451-63. doi: 10.2217/PGS.15.85. Epub 2015 Aug 28.
AIM
We investigate the role of ethnicity and admixture in drug response across a broad group of chemotherapeutic drugs. Also, we generate hypotheses on the genetic variants driving differential drug response through multivariate genome-wide association studies.
METHODS
Immortalized lymphoblastoid cell lines from 589 individuals (Hispanic or non-Hispanic/Caucasian) were used to investigate dose-response for 28 chemotherapeutic compounds. Univariate and multivariate statistical models were used to elucidate associations between genetic variants and differential drug response as well as the role of ethnicity in drug potency and efficacy.
RESULTS & CONCLUSION: For many drugs, the variability in drug response appears to correlate with self-reported race and estimates of genetic ancestry. Additionally, multivariate genome-wide association analyses offered interesting hypotheses governing these differential responses.
目的
我们研究种族和基因混合在广泛的化疗药物反应中的作用。此外，我们通过多变量全基因组关联研究，对驱动药物反应差异的基因变异提出假设。
方法
使用来自589名个体（西班牙裔或非西班牙裔/白种人）的永生化淋巴母细胞系，研究28种化疗化合物的剂量反应。使用单变量和多变量统计模型来阐明基因变异与药物反应差异之间的关联，以及种族在药物效力和疗效中的作用。
结果与结论
对于许多药物，药物反应的变异性似乎与自我报告的种族和遗传血统估计相关。此外，多变量全基因组关联分析提供了关于这些差异反应的有趣假设。
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