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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

Abstract

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.

Acknowledgement

Supported by : National Natural Science Funds

References

  1. Araki K, Yamashita T, Reddy N, et al (2010). Molecular disruption of NBS1 with targeted gene delivery enhances chemosensitisation in head and neck cancer. Br J Cancer, 103, 1822-30. https://doi.org/10.1038/sj.bjc.6605980
  2. Chen YC (2005). Overexpression of NBS1 contributes to transformation through the activation of phosphatidylinositol 3-Kinase/Akt. J Biol Chem, 280, 32505-11. https://doi.org/10.1074/jbc.M501449200
  3. Choudhury A, Elliott F, Iles MM, et al (2008). Analysis of variants in DNA damage signalling genes in bladder cancer. BMC Med Genetics, 9, 69.
  4. Dumon-Jones V, Frappart PO, Tong WM, et al (2003). Nbn heterozygosity renders mice susceptible to tumor formation and ionizing radiation-induced tumorigenesis. Cancer Res, 63, 7263-9.
  5. Eisenhauer EA, Therasse P, Bogaerts J, et al (2009). New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer, 45, 228-47. https://doi.org/10.1016/j.ejca.2008.10.026
  6. Futaki M, Liu JM (2001). Chromosomal breakage syndromes and the BRCA1 genome surveillance complex. Trends Mol Med, 7, 560-5. https://doi.org/10.1016/S1471-4914(01)02178-5
  7. Hsu DS, Chang SY, Liu CJ, et al (2010). Identification of increased NBS1 expression as a prognostic marker of squamous cell carcinoma of the oral cavity. Cancer Sci, 101, 1029-37. https://doi.org/10.1111/j.1349-7006.2009.01471.x
  8. Hsu HM, Wang HC, Chen ST, et al (2007). Breast cancer risk is associated with the genes encoding the DNA double-strand break repair Mre11/Rad50/Nbs1 complex. Cancer Epidemiol Biomarkers Prev, 16, 2024-32. https://doi.org/10.1158/1055-9965.EPI-07-0116
  9. Kelly K, Crowley J, Bunn PA Jr, et al (2001). Randomized phase III trial of paclitaxel plus carboplatin versus vinorelbine plus cisplatin in the treatment of patients with advanced non-- small-cell lung cancer: a Southwest Oncology Group trial. J Clin Oncol, 19, 3210-8. https://doi.org/10.1200/JCO.2001.19.13.3210
  10. Kobayashi J (2004). Molecular mechanism of the recruitment of NBS1/hMRE11/hRAD50 complex to DNA double-strand breaks: NBS1 binds to gamma-H2AX through FHA/BRCT domain. J Radiat Res (Tokyo), 45, 473-8. https://doi.org/10.1269/jrr.45.473
  11. Kobayashi J, Antoccia A, Tauchi H, et al (2004). NBS1 and its functional role in the DNA damage response. DNA Repair (Amst), 3, 855-61.
  12. Lan Q, Shen M, Berndt SI, et al (2005). Smoky coal exposure, NBS1 polymorphisms, p53 protein accumulation, and lung cancer risk in Xuan Wei, China. Lung Cancer, 49, 317-23. https://doi.org/10.1016/j.lungcan.2005.04.004
  13. Landi S, Gemignani F, Canzian F, et al (2006). DNA repair and cell cycle control genes and the risk of young-onset lung cancer. Cancer Res, 66, 11062-9. https://doi.org/10.1158/0008-5472.CAN-06-1039
  14. Le Chevalier T (2010). Adjuvant chemotherapy for resectable non-small-cell lung cancer: where is it going? Ann Oncol, 21, vii196. https://doi.org/10.1093/annonc/mdq376
  15. Li C, Wang LE, Wei Q (2009). DNA repair phenotype and cancer susceptibility-a mini review. Int J Cancer, 124, 999-1007. https://doi.org/10.1002/ijc.24126
  16. Loizidou MA, Cariolou MA, Neuhausen SL, et al (2010). Genetic variation in genes interacting with BRCA1/2 and risk of breast cancer in the Cypriot population. Breast Cancer Res Treat, 121, 147-56. https://doi.org/10.1007/s10549-009-0518-7
  17. Lu J, Wei Q, Bondy ML, et al (2006). Polymorphisms and haplotypes of the NBS1 gene are associated with risk of sporadic breast cancer in non-Hispanic white women https://doi.org/10.1093/carcin/bgl077
  18. Margulis V, Lin J, Yang H, et al (2008). Genetic susceptibility to renal cell carcinoma: the role of DNA double-strand break repair pathway. Cancer Epidemiol Biomarkers Prev, 17, 2366-73. https://doi.org/10.1158/1055-9965.EPI-08-0259
  19. Maser RS, Monsen KJ, Nelms BE, Petrini JH (1997). hMre11 and hRad50 nuclear foci are induced during the normal cellular response to DNA double-strand breaks. Mol Cell Biol, 17, 6087-96. https://doi.org/10.1128/MCB.17.10.6087
  20. Medina PP, Ahrendt SA, Pollan M, et al (2003). Screening of homologous recombination gene polymorphisms in lung cancer patients reveals an association of the NBS1- 185Gln variant and p53 gene mutations. Cancer Epidemiol Biomarkers Prev, 12, 699-704.
  21. MeiXia L, Jiachun L, XiaoBo Y, et al (2009). Association between the NBS1 E185Q polymorphism and cancer risk: a meta-analysis. BMC Cancer, 9, 124. https://doi.org/10.1186/1471-2407-9-124
  22. Merika M, Orkin SH (1993). DNA-binding specificity of GATA family transcription factors. Mol Cell Biol, 13, 3999-4010. https://doi.org/10.1128/MCB.13.7.3999
  23. Mosor M, Ziolkowska I, Januszkiewiczlewandowska D, Nowak J (2008). Polymorphisms and haplotypes of the NBS1 gene in childhood acute leukaemia. Eur J Cancer, 44, 2226-32. https://doi.org/10.1016/j.ejca.2008.06.026
  24. Naruke T, Tsuchiya R, Kondo H, Asamura H (2001). Prognosis and survival after resection for bronchogenic carcinoma based on the 1997 TNM-staging classification: the Japanese experience. Ann Thorac Surg, 71, 1759-64. https://doi.org/10.1016/S0003-4975(00)02609-6
  25. Ohe Y, Ohashi Y, Kubota K, et al (2007). Randomized phase III study of cisplatin plus irinotecan versus carboplatin plus paclitaxel, cisplatin plus gemcitabine, and cisplatin plus vinorelbine for advanced non-small-cell lung cancer: Four- Arm Cooperative Study in Japan. Ann Oncol, 18, 317-23.
  26. Ott K, Rachakonda PS, Panzram B, et al (2011). DNA repair gene and MTHFR gene polymorphisms as prognostic markers in locally advanced adenocarcinoma of the esophagus or stomach treated with cisplatin and 5-fluorouracil-based neoadjuvant chemotherapy. Ann Surg Oncol, 18, 2688-98. https://doi.org/10.1245/s10434-011-1601-y
  27. Park SL, Bastani D, Goldstein BY, et al (2010). Associations between NBS1 polymorphisms, haplotypes and smokingrelated cancers. Carcinogenesis, 31, 1264-71. https://doi.org/10.1093/carcin/bgq096
  28. Perez RP (1998). Cellular and molecular determinants of cisplatin resistance. Eur J Cancer, 34, 1535-42. https://doi.org/10.1016/S0959-8049(98)00227-5
  29. Ryk C, Kumar R, Thirumaran R, Hou S (2006). Polymorphisms in the DNA repair genes XRCC1, APEX1, XRCC3 and NBS1, and the risk for lung cancer in never- and eversmokers. Lung Cancer, 54, 285-92. https://doi.org/10.1016/j.lungcan.2006.08.004
  30. Scagliotti GV, De Marinis F, Rinaldi M, et al (2002). Phase III randomized trial comparing three platinum-based doublets in advanced non-small-cell lung cancer. J Clin Oncol, 20, 4285-91. https://doi.org/10.1200/JCO.2002.02.068
  31. Schiller JH, Harrington D, Belani CP, et al (2002). Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med, 346, 92-8. https://doi.org/10.1056/NEJMoa011954
  32. Schuetz JM, MacArthur AC, Leach S, et al (2009). Genetic variation in the NBS1, MRE11, RAD50 and BLM genes and susceptibility to non-Hodgkin lymphoma. BMC Med Genetics, 10, 117. https://doi.org/10.1186/1471-2350-10-117
  33. Siddik ZH (2003). Cisplatin: mode of cytotoxic action and molecular basis of resistance. Oncogene, 22, 7265-79. https://doi.org/10.1038/sj.onc.1206933
  34. Spiro SG, Silvestri GA (2005). The treatment of advanced nonsmall cell lung cancer. Curr Opin Pulm Med, 11, 287-91. https://doi.org/10.1097/01.mcp.0000166590.03042.56
  35. Stern MC, Lin J, Figueroa JD, et al (2009). Polymorphisms in DNA repair genes, smoking, and bladder cancer risk: findings from the international consortium of bladder cancer. Cancer Res, 69, 6857-64. https://doi.org/10.1158/0008-5472.CAN-09-1091
  36. Tauchi H (2000). Positional cloning and functional analysis of the gene responsible for Nijmegen breakage syndrome, NBS1. J Radiat Res, 41, 9-17.
  37. Tran H, Shi G, Li G, et al (2004). Mutant Nbs1 enhances cisplatin-induced DNA damage and cytotoxicity in head and neck cancer. Otolaryngol Head Neck Surg, 131, 477-84. https://doi.org/10.1016/j.otohns.2004.04.019
  38. Wang LE, Yin M, Dong Q, et al (2011). DNA repair capacity in peripheral lymphocytes predicts survival of patients with non-small-cell lung cancer treated with first-line platinumbased chemotherapy. J Clin Oncol, 29, 4121-8. https://doi.org/10.1200/JCO.2010.34.3616
  39. Wang Y, Cortez D, Yazdi P, et al (2000). BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures. Genes Dev, 14, 927-39.
  40. Yang MH (2006). Increased NBS1 expression is a marker of aggressive head and neck cancer and overexpression of NBS1 contributes to transformation. Clinic Cancer Res, 12, 507-15. https://doi.org/10.1158/1078-0432.CCR-05-1231
  41. Zhang Y, Zhou J, Lim CU (2006). The role of NBS1 in DNA double strand break repair, telomere stability, and cell cycle checkpoint control. Cell Res, 16, 45-54. https://doi.org/10.1038/sj.cr.7310007
  42. Zheng J, Zhang C, Jiang L, et al (2011). Functional NBS1 polymorphism is associated with occurrence and advanced disease status of nasopharyngeal carcinoma. Mol Carcinog, 50, 689-96. https://doi.org/10.1002/mc.20803
  43. Zienolddiny S (2005). Polymorphisms of DNA repair genes and risk of non-small cell lung cancer. Carcinogenesis, 27, 560-7. https://doi.org/10.1093/carcin/bgi232

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