Single nucleotide polymorphisms and outcome in docetaxel-cisplatin-treated advanced non-small-cell lung cancer
Single nucleotide polymorphisms and outcome in docetaxel-cisplatin-treated advanced non-small-cell lung cancer
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DOI：
10.1093/annonc/mdh319
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发表时间：
2004-08-01
影响因子：
50.5
通讯作者：
Lianes, P
中科院分区：
文献类型：
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作者：
Isla, D;Sarries, C;Lianes, P
背景：含铂的双联化疗是晚期非小细胞肺癌（NSCLC）的标准化疗。切除修复交叉互补蛋白1（ERCC 1）、着色性干皮病D组（XPD）和核糖核苷酸还原酶亚单位M1（RRM 1）对顺铂DNA加合物的修复至关重要。多药耐药1（MDR 1）与抗微管药物耐药有关。我们评估了ERCC 1、XPD、RRM 1和MDR 1的单核苷酸多态性（SNP）以及ERCC 1 mRNA表达是否预测了紫杉醇-顺铂治疗的IV期NSCLC患者的生存率。使用TaqMan 5'核酸酶测定法，我们检测了ERCC 1118、XPD 751和312、RRM 1 - 37 C/A，和MDR 1 C3435 T SNPs在外周血淋巴细胞（PBL）获得自62例紫杉醇-顺铂治疗的晚期NSCLC患者。ERCC 1的表达测定RNA分离PBLs使用实时逆转录酶PCR.Results：总体中位生存期为10.26个月。34例ERCC 1 118 C/T患者的中位生存期为9.67个月，17例T/T患者为9.74个月，而11例C/C患者未达到中位生存期（P=0.04）。根据ERCC I 118基因型，观察到进展时间的相似显著差异（P = 0.03）。结论：ERCC 1 118 C等位基因纯合子患者的生存率明显提高。ERCC 1 SNP评估可能是定制化疗试验的重要组成部分。
Background: Platinum-based doublets are the standard chemotherapy for advanced non-small-cell lung cancer (NSCLC). Excision-repair cross-complementing 1 (ERCC1), xeroderma pigmentosum group D (XPD) and ribonucleotide reductase subunit M1 (RRM1) are essential to the repair of cisplatin DNA adducts. Multidrug resistance 1 (MDR1) has been related to antimicrotubule resistance. We assessed whether single nucleotide polymorphisms (SNPs) in ERCC1, XPD, RRM1 and MDR1, and ERCC1 mRNA expression, predicted survival in docetaxel-cisplatin-treated stage IV NSCLC patients.Patients and methods: Using the TaqMan 5' nuclease assay, we examined ERCC1 118, XPD 751 and 312, RRM1 -37C/A, and MDR1 C3435T SNPs in peripheral blood lymphocytes (PBLs) obtained from 62 docetaxel-cisplatin-treated advanced NSCLC patients. ERCC1 expression was measured in RNA isolated from PBLs using real-time reverse transcriptase PCR.Results: Overall median survival was 10.26 months. Median survival was 9.67 months for 34 patients with ERCC1 118 C/T, 9.74 months for 17 patients with T/T, and not reached for I I patients with C/C (P=0.04). Similar significant differences in time to progression were observed according to ERCC I 118 genotype (P = 0.03). No other significant differences were observed.Conclusions: Patients homozygous for the ERCC1 118 C allele demonstrated a significantly better survival. ERCC1 SNP assessment could be an important component of tailored chemotherapy trials.