Heritability and linkage analysis of sensitivity to cisplatin-induced cytotoxicity
Heritability and linkage analysis of sensitivity to cisplatin-induced cytotoxicity
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DOI：
10.1158/0008-5472.can-04-0340
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发表时间：
2004-06-15
期刊：
影响因子：
11.2
通讯作者：
Badner, JA
中科院分区：
文献类型：
--
作者：
Dolan, ME;Newbold, KG;Badner, JA
关于解释化疗细胞毒性敏感性变化的遗传决定因素知之甚少。我们的特点是顺铂的敏感性程度，使用淋巴母细胞系来自10个中心d 'Etude du多态性人类谱系。我们估计对顺铂诱导的细胞毒性敏感性的遗传率接近0.47;因此，对顺铂细胞毒性作用的敏感性受到明显的遗传影响。进行连锁分析，最强的信号（Iod评分，2.16;经验P = 0.0005）被发现在染色体I上的44 cM。对顺铂诱导的细胞毒性的敏感性可能是由于多个位点，低位点特异性遗传力有助于性状。这些数据表明，使用大的谱系，已被广泛的基因分型的抗癌药物的细胞生长抑制敏感性的遗传贡献进行评估的权力。
Little is known about the genetic determinants explaining variation in sensitivity to chemotherapeutic cytotoxicity. We characterized the degree of cisplatin sensitivity, using lymphoblastoid cell lines derived from 10 Centre d'Etude du Polymorphisme Humain pedigrees. We estimated the heritability for susceptibility to cisplatin-induced cytotoxicity to be similar to0.47; therefore, sensitivity to the cytotoxic effects of cisplatin is under appreciable genetic influence. Linkage analysis was performed, and the strongest signal (Iod score, 2.16; empirical P = 0.0005) was found on chromosome I at 44 cM. Susceptibility to cisplatin-induced cytotoxicity is likely due to multiple loci, with low locus-specific heritability contributing to the trait. These data show the power of using large pedigrees that have been extensively genotyped for evaluating the genetic contribution to sensitivity to cell growth inhibition by anticancer agents.