Pharmacogenetics of the DNA repair pathways in advanced non-small cell lung cancer patients treated with platinum-based chemotherapy
Pharmacogenetics of the DNA repair pathways in advanced non-small cell lung cancer patients treated with platinum-based chemotherapy
复制标题
DOI：
10.1016/j.canlet.2014.07.023
复制
发表时间：
2014-10-28
期刊：
影响因子：
9.7
通讯作者：
Barnadas, Agusti
中科院分区：
文献类型：
--
作者：
Sullivan, Ivana;Salazar, Juliana;Barnadas, Agusti
DNA修复基因的遗传变异可能在非小细胞肺癌（NSCLC）铂基化疗的有效性中发挥作用。我们分析了8个基因（ERCC1、ERCC2、ERCC3、ERCC4、ERCC5、XPA、XRCC1和XRCC2）中涉及DNA修复机制及其与非小细胞肺癌预后相关的17个单核苷酸多态性。这项前瞻性研究包括接受铂类化疗的III期和IV期患者。所有患者（n = 161）接受顺铂或卡铂加第三代药物治疗。此外，IIIA期和IIIB期患者（n = 74）接受了伴随或序贯放疗。使用生物标记系统分析血液DNA样本中的种系多态性。我们发现，在III期患者中，疗效与ERCC1和ERCC3基因的snp显著相关，而放疗衍生的毒性与ERCC2基因的snp相关。在IV期患者中，反应与ERCC4基因的遗传变异和XRCC1基因的SNP相关。DNA修复机制的复杂性以及肺癌治疗的异质性可以解释多种基因作为患者预后的假定生物标志物的作用。2014爱思唯尔爱尔兰有限公司版权所有。
Genetic variants in DNA repair genes may play a role in the effectiveness of platinum-based chemotherapy in non-small cell lung cancer (NSCLC). We analyzed 17 SNPs in eight genes (ERCC1, ERCC2, ERCC3, ERCC4, ERCC5, XPA, XRCC1 and XRCC2) involved in DNA repair mechanisms and its association with outcome in NSCLC. This prospective study included patients with stages III and IV treated with platinum-based chemotherapy. All patients (n = 161) received cisplatin or carboplatin plus a third-generation drug. Additionally, stage IIIA and IIIB patients (n = 74) received concomitant or sequential radiotherapy. Germline polymorphisms were analyzed using the BioMark system in blood DNA samples. We found that in stage III patients, response was significantly associated with SNPs in ERCC1 and in ERCC3 genes, while radiotherapy-derived toxicity correlated with SNPs in the ERCC2 gene. In stage IV patients, response was associated with a genetic variant in the ERCC4 gene and survival with a SNP in the XRCC1 gene. The complexity of the DNA repair mechanisms along with the heterogeneity in the treatment of lung cancer could explain the role of multiple genes as putative biomarkers of patient outcome. (C) 2014 Elsevier Ireland Ltd. All rights reserved.