The impact of functional LIG4 polymorphism on platinum-based chemotherapy response and survival in non-small cell lung cancer.
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.
Department of Thoracic Surgery, Zhejiang Cancer Hospital, Hangzhou, 310022, Zhejiang, China.
You-Hua
YH
Jiang
Xiao-Ling
XL
Xu
Hai-Hong
HH
Ruan
Wei-Zhen
WZ
Xu
Dan
D
Li
Jian-Guo
JG
Feng
Qian-Bo
QB
Han
Wei-Min
WM
Mao
D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000556:secondary; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000556:secondary; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000556:secondary; D018797:Cell Cycle Proteins / Q000235:genetics; D002945:Cisplatin / Q000008:administration & dosage; D000072481:DNA Ligase ATP; D011088:DNA Ligases / Q000235:genetics*; D004260:DNA Repair; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000235:genetics; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D011446:Prospective Studies; D051135:Rad51 Recombinase / Q000235:genetics; D015996:Survival Rate
D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; C000607893:LIG4 protein, human; C112156:NBN protein, human; D009687:Nuclear Proteins; D016190:Carboplatin; D051135:Rad51 Recombinase; D011088:DNA Ligases; D000072481:DNA Ligase ATP; D002945:Cisplatin