UNC Institute for Pharmacogenomics & Individualized Therapy, University of North Carolina, Chapel Hill, NC 27599-7361, USA.
Pharmacogenomics. 2011 Oct;12(10):1407-15. doi: 10.2217/pgs.11.92.
Individualization of cancer chemotherapy based on the patient's genetic makeup holds promise for reducing side effects and improving efficacy. However, the relative contribution of genetics to drug response is unknown.
MATERIALS & METHODS: In this study, we investigated the cytotoxic effect of 29 commonly prescribed chemotherapeutic agents from diverse drug classes on 125 lymphoblastoid cell lines derived from 14 extended families.
The results of this systematic study highlight the variable role that genetics plays in response to cytotoxic drugs, ranging from a heritability of <0.15 for gemcitabine to >0.60 for epirubicin.
Putative quantitative trait loci for cytotoxic response were identified, as well as drug class-specific signatures, which could indicate possible shared genetic mechanisms. In addition to the identification of putative quantitative trait locis, the results of this study inform the prioritization of chemotherapeutic drugs with a sizable genetic response component for future investigation.
基于患者的基因构成对癌症化疗进行个体化治疗有望减少副作用并提高疗效。然而，遗传因素对药物反应的相对贡献尚不清楚。
在这项研究中，我们研究了来自 14 个扩展家族的 125 个淋巴母细胞系对 29 种常用化疗药物的细胞毒性作用。
这项系统研究的结果突出了遗传因素在细胞毒性药物反应中的不同作用，从吉西他滨的遗传率<0.15 到表柔比星的遗传率>0.60 不等。
确定了细胞毒性反应的推定数量性状基因座，以及药物类别特异性特征，这可能表明存在可能的共享遗传机制。除了鉴定推定的数量性状基因座外，本研究的结果还为具有相当大遗传反应成分的化疗药物的未来研究提供了信息，以确定优先次序。
