Association of DNA Repair Gene Polymorphisms With Response to Platinum-Based Doublet Chemotherapy in Patients With Non-Small-Cell Lung Cancer
Association of DNA Repair Gene Polymorphisms With Response to Platinum-Based Doublet Chemotherapy in Patients With Non-Small-Cell Lung Cancer
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DOI：
10.1200/jco.2010.30.5334
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发表时间：
2010-11-20
影响因子：
45.3
通讯作者：
Kunitoh, Hideo
中科院分区：
文献类型：
--
作者：
Shiraishi, Kouya;Kohno, Takashi;Kunitoh, Hideo
目的鉴定影响非小细胞肺癌（NSCLC）患者对铂基双重化疗反应的DNA修复基因多态性。患者和方法2000 - 2008年，在日本国立癌症中心医院接受铂类双重化疗的640例非小细胞肺癌患者参与了一项27个DNA修复基因中30个单核苷酸多态性（snp）的应答与基因型关系的研究，这些患者的应答采用实体肿瘤应答评价标准（RECIST）进行评价。候选snp从201例患者中选择，并通过预先指定的P值标准在439例独立患者中验证其相关性。结果不论何种治疗方案，TP53基因Arg72Pro SNP的小等位基因TP53- 72pro纯合子的应答率（54.3%）均高于大等位基因TP53- 72arg的应答率（29.1%,P = 4.4 X 10(-5)），小等位基因纯合子的无进展生存期和总生存期均明显高于大等位基因纯合子（风险比[HR] 0.85, 95% CI 0.74 ~ 0.98, P = 0.020, HR 0.86, 95% CI 0.74 ~ 0.99, P = 0.039）。聚（adp -核糖）聚合酶1 （PARP1）基因中SNP Lys940Arg的少量等位基因携带者对紫杉醇方案的应答率（45.8%）优于对吉西他滨方案的应答率（10.5%，相互作用P = 0.019）。结论TP53和PARP1基因的多态性参与了NSCLC患者对铂类双重化疗反应的个体差异。[J]中华临床杂志，28(4):445 - 452。(c) 2010年由美国临床肿瘤学会发布
Purpose To identify polymorphisms in DNA repair genes that affect responses to platinum-based doublet chemotherapy in patients with non-small-cell lung cancer (NSCLC).Patients and Methods In total, 640 patients with NSCLC who received platinum-based doublet chemotherapy in the National Cancer Center Hospital in Japan from 2000 to 2008 and whose responses were evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) participated in a study of the association between response and genotypes for 30 single nucleotide polymorphisms (SNPs) in 27 DNA repair genes. Candidate SNPs were selected in a discovery set of 201 patients, and their associations were validated in an independent set of 439 patients by prespecified P value criteria.Results Homozygotes for the minor allele TP53-72Pro of the Arg72Pro SNP in the TP53 gene showed a better response rate (54.3%) than those for the major allele TP53-72Arg (29.1%; P = 4.4 X 10(-5)) irrespective of therapeutic regimens, and minor allele homozygotes had significantly longer progression-free and overall survivals than major allele homozygotes (hazard ratio [HR], 0.85; 95% CI, 0.74 to 0.98; P = .020; and HR, 0.86; 95% CI, 0.74 to 0.99; P = .039). Minor allele carriers for SNP Lys940Arg in the poly (ADP-ribose) polymerase 1 (PARP1) gene showed a better response rate to the paclitaxel regimen (45.8%) than to the gemcitabine regimen (10.5%; P for interaction = .019).Conclusion Polymorphisms in the TP53 and PARP1 genes are involved in inter-individual differences in the response to platinum-based doublet chemotherapy in patients with NSCLC. J Clin Oncol 28:4945-4952. (c) 2010 by American Society of Clinical Oncology