Jiang You-Hua, Xu Xiao-Ling, Ruan Hai-Hong, Xu Wei-Zhen, Li Dan, Feng Jian-Guo, Han Qian-Bo, Mao Wei-Min
Department of Thoracic Surgery, Zhejiang Cancer Hospital, Hangzhou, 310022, Zhejiang, China.
Med Oncol. 2014 May;31(5):959. doi: 10.1007/s12032-014-0959-7. Epub 2014 Apr 11.
DNA repair capacity is correlated with the sensitivity of cancer cells toward platinum-based chemotherapy. The aim of this study was to investigate whether single-nucleotide polymorphisms (SNPs) in DNA repair genes NBS1, LIG4, and RAD51 were correlated with tumor response in advanced non-small cell lung cancer (NSCLC) patients in a Chinese population who received platinum-based chemotherapy. The treatment outcomes of 146 advanced NSCLC patients who were treated with platinum-based chemotherapy were evaluated. The polymorphic status of three SNPs was determined by genotyping via the polymerase chain reaction-restriction fragment length polymorphism method. Forty-five patients in the group with the CC genotype (45/90) showed a good response to treatment, while only 18 patients in the CT+TT group (18/55) showed a good response, indicating a substantial differences in the chemotherapy response rate based on the LIG4 Thr9Ile polymorphism (P = 0.042). Patients with the GG genotype for the NSB1 Glu185Gln polymorphism were more sensitive to platinum-based chemotherapy compared with patients with either the CG or CC genotype (P = 0.001). Kaplan-Meier analysis of all patients showed a significant association between the LIG4 Thr9Ile CC polymorphism and superior progression-free survival and overall survival (log-rank P = 0.045 and 0.031, respectively). However, there were no significant differences in survival based on the LIG4 Thr9Ile or the RAD51 135G>C polymorphisms. Polymorphisms in the NSB1 and LIG4 genes may be a predictive marker for treatment response and for advanced NSCLC patients in stage IIIB + IV. The CC genotype of the LIG4 Thr9Ile polymorphism may also serve as an independent prognosis factor.
DNA修复能力与癌细胞对铂类化疗的敏感性相关。本研究旨在调查DNA修复基因NBS1、LIG4和RAD51中的单核苷酸多态性（SNP）是否与接受铂类化疗的中国人群晚期非小细胞肺癌（NSCLC）患者的肿瘤反应相关。评估了146例接受铂类化疗的晚期NSCLC患者的治疗结果。通过聚合酶链反应-限制性片段长度多态性方法进行基因分型，确定了三个SNP的多态性状态。CC基因型组中的45例患者（45/90）对治疗反应良好，而CT+TT组中只有18例患者（18/55）反应良好，这表明基于LIG4 Thr9Ile多态性的化疗反应率存在显著差异（P = 0.042）。与CG或CC基因型患者相比，NSB1 Glu185Gln多态性的GG基因型患者对铂类化疗更敏感（P = 0.001）。对所有患者进行的Kaplan-Meier分析显示，LIG4 Thr9Ile CC多态性与无进展生存期和总生存期的延长显著相关（对数秩检验P分别为0.045和0.031）。然而，基于LIG4 Thr9Ile或RAD51 135G>C多态性的生存期无显著差异。NSB1和LIG4基因中的多态性可能是IIIB+IV期晚期NSCLC患者治疗反应的预测标志物。LIG4 Thr9Ile多态性的CC基因型也可能作为独立的预后因素。
