Genetic Variants of NBS1 Predict Clinical Outcome of Platinum-based Chemotherapy in Advanced Non-small Cell Lung Cancer in Chinese

  • Xu, Jia-Li (Department of Oncology, The First Affiliated Hospital of Nanjing Medical University) ;
  • Hu, Ling-Min (Department of Epidemiology and Biostatistics, MOE Key Laboratory of Modern Toxicology, School of Public Health, Nanjing Medical University) ;
  • Huang, Ming-De (Department of Oncology, Huai'an No.1 hospital affiliated to Nanjing Medical University) ;
  • Zhao, Wan (Department of Oncology, The First Affiliated Hospital of Nanjing Medical University) ;
  • Yin, Yong-Mei (Department of Oncology, The First Affiliated Hospital of Nanjing Medical University) ;
  • Hu, Zhi-Bin (Department of Epidemiology and Biostatistics, MOE Key Laboratory of Modern Toxicology, School of Public Health, Nanjing Medical University) ;
  • Ma, Hong-Xia (Department of Epidemiology and Biostatistics, MOE Key Laboratory of Modern Toxicology, School of Public Health, Nanjing Medical University) ;
  • Shen, Hong-Bing (Department of Epidemiology and Biostatistics, MOE Key Laboratory of Modern Toxicology, School of Public Health, Nanjing Medical University) ;
  • Shu, Yong-Qian (Department of Oncology, The First Affiliated Hospital of Nanjing Medical University)
  • Published : 2012.03.31


Objective: NBS1 plays a key role in the repair of DNA double-strand break (DSB). We conducted this study to investigate the effect of two critical polymorphisms (rs1805794 and rs13312840) in NBS1 on treatment response and prognosis of advanced non-small cell lung cancer (NSCLC) patients with platinum-based chemotherapy. Methods: Using TaqMan methods, we genotyped the two polymorphisms in 147 NSCLC patients. Odds ratios (ORs) and their 95% confidential intervals (CIs) were calculated as a measure of difference in the response rate of platinum-based chemotherapy using logistic regression analysis. The Kaplan-Meier and log-rank tests were used to assess the differences in progression-free survival (PFS) and overall survival (OS). Cox proportional hazards model was applied to assess the hazard ratios (HRs) for PFS and OS. Results: Neither of the two polymorphisms was significantly associated with treatment response of platinum-based chemotherapy. However, patients carrying the rs1805794 CC variant genotype had a significantly improved PFS compared to those with GG genotype (16.0 vs. 8.0 months, P = 0.040). Multivariable cox regression analysis further showed that rs1805974 was a significantly favorable prognostic factor for PFS [CC/CG vs. GG: Adjusted HR = 0.62, 95% CI: 0.39-0.99; CC vs. CG/GG: Adjusted HR = 0.56, 95% CI: 0.32-0.97). Similarly, rs13312840 with a small sample size also showed a significant association with PFS (CC vs. CT/TT: Adjusted HR = 25.62, 95% CI: 1.53-428.39). Conclusions: Our findings suggest that NBS1 polymorphisms may be genetic biomarkers for NSCLC prognosis especially PFS with platinum-based chemotherapy in the Chinese population.


Supported by : National Natural Science Funds


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