Tumor Biology

, Volume 35, Issue 11, pp 10723–10729 | Cite as

NBS1 Glu185Gln polymorphism and susceptibility to urinary system cancer: a meta-analysis

  • Ying Zhang
  • Yu-Shan Huang
  • Wen-Qian Lin
  • Shao-Dan Zhang
  • Qi-Wen Li
  • Ye-Zhu Hu
  • Rong-Liang Zheng
  • Tao Tang
  • Xi-Zhao Li
  • Xiao-Hui Zheng
Research Article


A number of studies have investigated the association between the NBS1 Glu185Gln (rs1805794, 8360 G > C) polymorphism and risk for urinary system cancer including bladder cancer, prostate cancer, and renal cell cancer; however, the findings are conflicting. We conducted a meta-analysis focusing on eight published studies with 3,542 cases and 4,210 controls to derive a more precise evaluation of the relationship between the NBS1 Glu185Gln polymorphism and urinary system cancer susceptibility. Overall, the NBS1 Glu185Gln polymorphism was significantly related to increased risk for urinary system cancer (homozygous model: odds ratio (OR) = 1.23, 95 % confidence interval (95 % CI) = 1.05–1.44, p = 0.011; heterozygous model: OR = 1.14, 95 % CI = 1.04–1.26, p = 0.008; dominant model: OR = 1.16, 95 % CI = 1.05–1.27, p = 0.002; and Gln vs. Glu: OR = 1.12, 95 % CI = 1.04–1.20, p = 0.002) and further stratification analysis indicated an increased risk for bladder cancer (heterozygous model: OR = 1.13, 95 % CI = 1.02–1.26, p = 0.022; dominant model: OR = 1.14, 95 % CI = 1.03–1.26, p = 0.014; and Gln vs. Glu: OR = 1.09, 95 % CI = 1.01–1.18, p = 0.023) and Caucasian populations (homozygous model: OR = 1.33, 95 % CI = 1.11–1.59, p = 0.002; heterozygous model: OR = 1.16, 95 % CI = 1.04–1.30, p = 0.009; dominant model: OR = 1.19, 95 % CI = 1.07–1.32, p = 0.001; and Gln vs. Glu: OR = 1.15, 95 % CI = 1.06–1.25, p < 0.001). Despite some limitations, this meta-analysis established some solid statistical evidence for the association between NBS1 Glu185Gln polymorphism and increased risk for urinary system cancer, especially for bladder cancer, but more well-designed prospective studies are needed to further verify our findings.


NBS1 Glu185Gln Urinary system cancer Meta-analysis 


Conflict of interest



  1. 1.
    Jemal A et al. Global cancer statistics. CA Cancer J Clin. 2011;61(2):69–90.PubMedCrossRefGoogle Scholar
  2. 2.
    Mohrenweiser HW, Wilson 3rd DM, Jones IM. Challenges and complexities in estimating both the functional impact and the disease risk associated with the extensive genetic variation in human DNA repair genes. Mutat Res. 2003;526(1–2):93–125.PubMedCrossRefGoogle Scholar
  3. 3.
    Wood RD et al. Human DNA repair genes. Science. 2001;291(5507):1284–9.PubMedCrossRefGoogle Scholar
  4. 4.
    Kuschel B et al. Variants in DNA double-strand break repair genes and breast cancer susceptibility. Hum Mol Genet. 2002;11(12):1399–407.PubMedCrossRefGoogle Scholar
  5. 5.
    Khanna KK, Jackson SP. DNA double-strand breaks: signaling, repair and the cancer connection. Nat Genet. 2001;27(3):247–54.PubMedCrossRefGoogle Scholar
  6. 6.
    van Gent DC, Hoeijmakers JH, Kanaar R. Chromosomal stability and the DNA double-stranded break connection. Nat Rev Genet. 2001;2(3):196–206.PubMedCrossRefGoogle Scholar
  7. 7.
    Yang L et al. A functional polymorphism at microRNA-629-binding site in the 3′-untranslated region of NBS1 gene confers an increased risk of lung cancer in southern and eastern Chinese population. Carcinogenesis. 2012;33(2):338–47.PubMedCrossRefGoogle Scholar
  8. 8.
    Jackson SP. Sensing and repairing DNA double-strand breaks. Carcinogenesis. 2002;23(5):687–96.PubMedCrossRefGoogle Scholar
  9. 9.
    Lu J et al. Polymorphisms and haplotypes of the NBS1 gene are associated with risk of sporadic breast cancer in non-Hispanic white women <or=55 years. Carcinogenesis. 2006;27(11):2209–16.PubMedCrossRefGoogle Scholar
  10. 10.
    Kobayashi J et al. NBS1 and its functional role in the DNA damage response. DNA Repair (Amst). 2004;3(8–9):855–61.CrossRefGoogle Scholar
  11. 11.
    Matsuura S et al. Nijmegen breakage syndrome and DNA double strand break repair by NBS1 complex. Adv Biophys. 2004;38(Complete):65–80.CrossRefGoogle Scholar
  12. 12.
    Paull TT, Lee JH. The Mre11/Rad50/Nbs1 complex and its role as a DNA double-strand break sensor for ATM. Cell Cycle. 2005;4(6):737–40.PubMedCrossRefGoogle Scholar
  13. 13.
    Matsuura S et al. Positional cloning of the gene for Nijmegen breakage syndrome. Nat Genet. 1998;19(2):179–81.PubMedCrossRefGoogle Scholar
  14. 14.
    Varon R et al. Nibrin, a novel DNA double-strand break repair protein, is mutated in Nijmegen breakage syndrome. Cell. 1998;93(3):467–76.PubMedCrossRefGoogle Scholar
  15. 15.
    Dumon-Jones V et al. Nbn heterozygosity renders mice susceptible to tumor formation and ionizing radiation-induced tumorigenesis. Cancer Res. 2003;63(21):7263–9.PubMedGoogle Scholar
  16. 16.
    Zhang Y, Zhou J, Lim CU. The role of NBS1 in DNA double strand break repair, telomere stability, and cell cycle checkpoint control. Cell Res. 2006;16(1):45–54.PubMedCrossRefGoogle Scholar
  17. 17.
    Park SL et al. Associations between NBS1 polymorphisms, haplotypes and smoking-related cancers. Carcinogenesis. 2010;31(7):1264–71.PubMedCentralPubMedCrossRefGoogle Scholar
  18. 18.
    Smith TR et al. Polygenic model of DNA repair genetic polymorphisms in human breast cancer risk. Carcinogenesis. 2008;29(11):2132–8.PubMedCentralPubMedCrossRefGoogle Scholar
  19. 19.
    Auranen A et al. Polymorphisms in DNA repair genes and epithelial ovarian cancer risk. Int J Cancer. 2005;117(4):611–8.PubMedCrossRefGoogle Scholar
  20. 20.
    Loizidou MA et al. Genetic variation in genes interacting with BRCA1/2 and risk of breast cancer in the Cypriot population. Breast Cancer Res Treat. 2010;121(1):147–56.PubMedCrossRefGoogle Scholar
  21. 21.
    Silva SN et al. Breast cancer risk and common single nucleotide polymorphisms in homologous recombination DNA repair pathway genes XRCC2, XRCC3, NBS1 and RAD51. Cancer Epidemiol. 2010;34(1):85–92.PubMedCrossRefGoogle Scholar
  22. 22.
    Zienolddiny S et al. Polymorphisms of DNA repair genes and risk of non-small cell lung cancer. Carcinogenesis. 2006;27(3):560–7.PubMedCrossRefGoogle Scholar
  23. 23.
    Lan Q et al. Smoky coal exposure, NBS1 polymorphisms, p53 protein accumulation, and lung cancer risk in Xuan Wei. China Lung Cancer. 2005;49(3):317–23.CrossRefGoogle Scholar
  24. 24.
    Sanyal S et al. Polymorphisms in DNA repair and metabolic genes in bladder cancer. Carcinogenesis. 2004;25(5):729–34.PubMedCrossRefGoogle Scholar
  25. 25.
    Figueroa JD et al. Evaluation of genetic variation in the double-strand break repair pathway and bladder cancer risk. Carcinogenesis. 2007;28(8):1788–93.PubMedCrossRefGoogle Scholar
  26. 26.
    Choudhury A et al. Analysis of variants in DNA damage signalling genes in bladder cancer. BMC Med Genet. 2008;9:69.PubMedCentralPubMedCrossRefGoogle Scholar
  27. 27.
    Broberg K et al. Constitutional short telomeres are strong genetic susceptibility markers for bladder cancer. Carcinogenesis. 2005;26(7):1263–71.PubMedCrossRefGoogle Scholar
  28. 28.
    Wu X et al. Bladder cancer predisposition: a multigenic approach to DNA-repair and cell-cycle-control genes. Am J Hum Genet. 2006;78(3):464–79.PubMedCentralPubMedCrossRefGoogle Scholar
  29. 29.
    Matullo G et al. DNA repair polymorphisms and cancer risk in non-smokers in a cohort study. Carcinogenesis. 2006;27(5):997–1007.PubMedCrossRefGoogle Scholar
  30. 30.
    Hebbring SJ et al. Role of the Nijmegen breakage syndrome 1 gene in familial and sporadic prostate cancer. Cancer Epidemiol Biomarkers Prev. 2006;15(5):935–8.PubMedCrossRefGoogle Scholar
  31. 31.
    Margulis V et al. Genetic susceptibility to renal cell carcinoma: the role of DNA double-strand break repair pathway. Cancer Epidemiol Biomarkers Prev. 2008;17(9):2366–73.PubMedCentralPubMedCrossRefGoogle Scholar
  32. 32.
    Mantel N, Haenszel W. Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst. 1959;22(4):719–48.PubMedGoogle Scholar
  33. 33.
    DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7(3):177–88.PubMedCrossRefGoogle Scholar
  34. 34.
    Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21(11):1539–58.PubMedCrossRefGoogle Scholar
  35. 35.
    Egger M et al. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315(7109):629–34.PubMedCentralPubMedCrossRefGoogle Scholar
  36. 36.
    Silva J et al. DNA repair system and prostate cancer progression: the role of NBS1 polymorphism (rs1805794). DNA Cell Biol. 2012;31(7):1182–6.PubMedCrossRefGoogle Scholar
  37. 37.
    He YZ et al. NBS1 Glu185Gln polymorphism and cancer risk: update on current evidence. Tumour Biol. 2014;35(1):675–87.PubMedCrossRefGoogle Scholar
  38. 38.
    Lu M et al. Association between the NBS1 E185Q polymorphism and cancer risk: a meta-analysis. BMC Cancer. 2009;9:124.PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Ying Zhang
    • 1
  • Yu-Shan Huang
    • 2
  • Wen-Qian Lin
    • 3
  • Shao-Dan Zhang
    • 1
  • Qi-Wen Li
    • 4
  • Ye-Zhu Hu
    • 1
  • Rong-Liang Zheng
    • 5
  • Tao Tang
    • 6
  • Xi-Zhao Li
    • 1
  • Xiao-Hui Zheng
    • 1
  1. 1.State Key Laboratory of Oncology in South China, Blood Transfusion Department, Collaborative Innovation Center for Cancer MedicineSun Yat-Sen University Cancer CenterGuangzhouChina
  2. 2.Department of Molecular PathologyGuangzhou Kingmed Center for Clinical LaboratoryGuangzhouChina
  3. 3.Department of Anesthesiology, State Key Laboratory of Oncology on Southern China, Cancer CenterSun Yat-Sen UniversityGuangzhouChina
  4. 4.Department of Radiation Oncology, State Key Laboratory of Oncology in South ChinaSun Yat-Sen University Cancer CenterGuangzhouChina
  5. 5.Department of Nuclear MedicineSun Yat-Sen University Cancer CenterGuangzhouChina
  6. 6.Department of Molecular DiagnosticsSun Yat-Sen University Cancer CenterGuangzhouChina

Personalised recommendations