The impact of functional LIG4 polymorphism on platinum-based chemotherapy response and survival in non-small cell lung cancer

• DOI: 10.1007/s12032-014-0959-7
• Publication Date: 2014-04-10T09:45:11Z
• Authors: You-Hua Jiang; Xiao-Ling Xu; Hai-Hong Ruan; Wei-Zhen Xu; Dan Li; Jian-Guo Feng; Qian-Bo Han; Wei-Min Mao
• Keywords: Male; Lung Neoplasms; DNA Ligases; DNA Repair; Nuclear Proteins; Cell Cycle Proteins; Adenocarcinoma; Middle Aged; Carboplatin; 3. Good health; DNA Ligase ATP; 03 medical and health sciences; 0302 clinical medicine; Carcinoma, Non-Small-Cell Lung; Lymphatic Metastasis; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Carcinoma, Squamous Cell; Humans; Female; Cisplatin; Follow-Up Studies; Neoplasm Staging

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.