Tumor Biology

, Volume 35, Issue 10, pp 10129–10136 | Cite as

ERCC polymorphisms and prognosis of patients with osteosarcoma

  • Jinsong Li
  • Shaohua Liu
  • Weiguo Wang
  • Kexiang Zhang
  • Zhendong Liu
  • Chaoyue Zhang
  • Shijie Chen
  • Song Wu
Research Article


Osteosarcoma is the most common primary bone malignancy in children and teenagers, and its clinical outcome remains poor. Previous studies have investigated the association between excision repair cross-complementing (ERCC) and prognosis of osteosarcoma patients, but their results were inconsistent. We aimed to clarify the associations between ERCC polymorphisms and osteosarcoma prognosis by using meta-analysis. We searched relevant studies in PubMed, Embase, coupled with Chinese National Knowledge Infrastructure (CNKI) in human osteosarcoma published prior to April, 2014. Hazard ratios (HR) together with their 95 % confidence intervals (95 % CI) were used to measure the relationship between ERCC mutations and prognosis in patients with osteosarcoma. Pooled results showed that polymorphism of ERCC2 Lys751Gln was associated with the overall survival of osteosarcoma (GG vs. AA, HR = 0.40; 95 % CI 0.18–0.86), and ERCC5 His46His mutation was associated with the event-free survival of osteosarcoma (CC vs. TT, HR = 0.37; 95 % CI 0.15, 0.93). In addition, there is no evidence of association on ERCC1 Asn118Asn, ERCC1 Gln504Lys, and ERCC2 Asp312Asn polymorphisms with prognosis in osteosarcoma. In summary, the ERCC2 Lys751Gln and ERCC5 His46His polymorphisms might influence osteosarcoma prognosis.


ERCC Osteosarcoma Polymorphisms Prognosis 


Conflict of interests



  1. 1.
    Hattinger CM, Pasello M, Ferrari S, Picci P, Serra M. Emerging drugs for high-grade osteosarcoma. Expert Opin Drug Saf. 2010;15:615–34.Google Scholar
  2. 2.
    Marina N, Gebhardt M, Teot L, Gorlick R. Biology and therapeutic advances for pediatric osteosarcoma. Oncologist. 2004;9:422–41.CrossRefPubMedGoogle Scholar
  3. 3.
    Fletcher CD, Unni KK, Mertens F: Pathology and genetics of tumours of soft tissue and bone. Iarc, 2002.Google Scholar
  4. 4.
    Bai SB, Chen HX, Bao YX, Luo X, Zhong JJ. Predictive impact of common variations in DNA repair genes on clinical outcome of osteosarcoma. Asian Pacific journal of cancer prevention : APJCP. 2013;14:3677–80.CrossRefPubMedGoogle Scholar
  5. 5.
    Chou AJ, Gorlick R. Chemotherapy resistance in osteosarcoma: Current challenges and future directions. Expert Rev Anticancer Ther. 2006;6:1075–85.CrossRefPubMedGoogle Scholar
  6. 6.
    Longhi A, Errani C, De Paolis M, Mercuri M, Bacci G. Primary bone osteosarcoma in the pediatric age: state of the art. Cancer Treat Rev. 2006;32:423–36.CrossRefPubMedGoogle Scholar
  7. 7.
    Sun XH, Hou WG, Zhao HX, Zhao YL, Ma C, Liu Y. Single nucleotide polymorphisms in the NER pathway and clinical outcome of patients with bone malignant tumors. Asian Pacific journal of cancer prevention: APJCP. 2013;14:2049–52.CrossRefPubMedGoogle Scholar
  8. 8.
    Goode EL, Ulrich CM, Potter JD. Polymorphisms in DNA repair genes and associations with cancer risk. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2002;11:1513–30.Google Scholar
  9. 9.
    Jones AR, Bell-Horwath TR, Li G, Rollmann SM, Merino EJ. Novel oxidatively activated agents modify DNA and are enhanced by ERCC1 silencing. Chem Res Toxicol. 2012;25:2542–52.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Shannon M, Lamerdin JE, Richardson L, McCutchen-Maloney SL, Hwang MH, Handel MA, et al. Characterization of the mouse xpf DNA repair gene and differential expression during spermatogenesis. Genomics. 1999;62:427–35.CrossRefPubMedGoogle Scholar
  11. 11.
    Lu B, Li J, Gao Q, Yu W, Yang Q, Li X. Laryngeal cancer risk and common single nucleotide polymorphisms in nucleotide excision repair pathway genes ercc1, ercc2, ercc3, ercc4, ercc5 and xpa. Gene. 2014;542:64–8.CrossRefPubMedGoogle Scholar
  12. 12.
    Wu Y, Yang Y: Complex association between ercc2 gene polymorphisms, gender, smoking and the susceptibility to bladder cancer: A meta-analysis. Tumor Biology 2014;35:1–13.Google Scholar
  13. 13.
    Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol. 2010;25:603–5.CrossRefPubMedGoogle Scholar
  14. 14.
    Higgins J, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21:1539–58.CrossRefPubMedGoogle Scholar
  15. 15.
    Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. Br Med J. 2003;327:557.CrossRefGoogle Scholar
  16. 16.
    Egger M, Smith GD, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315:629–34.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Stuck AE, Rubenstein LZ, Wieland D. Bias in meta-analysis detected by a simple, graphical test. Asymmetry detected in funnel plot was probably due to true heterogeneity BMJ. Br Med J. 1998;316:469.CrossRefGoogle Scholar
  18. 18.
    Yang L-M, Li X-H, Bao C-F. Glutathione s-transferase p1 and DNA polymorphisms with the response to chemotherapy and the prognosis of bone tumor. Asian Pacific Journal of Cancer Prevention. 2012;13:5883–6.CrossRefPubMedGoogle Scholar
  19. 19.
    Hao T, Feng W, Zhang J, Sun Y-J, Wang G. Association of four ercc1 and ercc2 SNPS with survival of bone tumour patients. Asian Pacific journal of cancer prevention : APJCP. 2012;13:3821–4.CrossRefPubMedGoogle Scholar
  20. 20.
    Caronia D, Patino-Garcia A, Milne RL, Zalacain-Diez M, Pita G, Alonso MR, et al. Common variations in ercc2 are associated with response to cisplatin chemotherapy and clinical outcome in osteosarcoma patients. Pharmacogenomics. 2009;9:347–53.CrossRefGoogle Scholar
  21. 21.
    Biason P, Hattinger C, Innocenti F, Talamini R, Alberghini M, Scotlandi K, et al. Nucleotide excision repair gene variants and association with survival in osteosarcoma patients treated with neoadjuvant chemotherapy. The pharmacogenomics journal. 2012;12:476–83.CrossRefPubMedGoogle Scholar
  22. 22.
    Clark JC, Dass CR, Choong PF. A review of clinical and molecular prognostic factors in osteosarcoma. J Cancer Res Clin Oncol. 2008;134:281–97.CrossRefPubMedGoogle Scholar
  23. 23.
    Caronia D, Patino-Garcia A, Milne R, Zalacain-Diez M, Pita G, Alonso M, et al. Common variations in ercc2 are associated with response to cisplatin chemotherapy and clinical outcome in osteosarcoma patients. The pharmacogenomics journal. 2009;9:347–53.CrossRefPubMedGoogle Scholar
  24. 24.
    Friedberg EC, Walker GC, Siede W: DNA repair and mutagenesis. American Society for Microbiology (ASM), 1995.Google Scholar
  25. 25.
    Aiub CAF, Mazzei JL, Pinto LFR, Felzenszwalb I. Participation of BER and NER pathways in the repair of DNA lesions induced at low < i > n</i > −nitrosodiethylamine concentrations. Toxicol Lett. 2004;154:133–42.CrossRefPubMedGoogle Scholar
  26. 26.
    Hoeijmakers JH. Genome maintenance mechanisms for preventing cancer. Nature. 2001;411:366–74.CrossRefPubMedGoogle Scholar
  27. 27.
    Lunn RM, Helzlsouer KJ, Parshad R, Umbach DM, Harris EL. Sanford KK Bell DA: Xpd polymorphisms: effects on DNA repair proficiency. Carcinogenesis. 2000;21:551–5.CrossRefPubMedGoogle Scholar
  28. 28.
    Qiao Y, Spitz MR, Shen H, Guo Z, Shete S, Hedayati M, Grossman L, Mohrenweiser H, Wei Q: Modulation of repair of ultraviolet damage in the host-cell reactivation assay by polymorphic xpc and xpd/ercc2 genotypes. carcinogenesis 2002;23:295–299.Google Scholar
  29. 29.
    Au WW, Salama SA. Functional characterization of polymorphisms in DNA repair genes using cytogenetic challenge assays. Environ Health Perspect. 2003;111:1843.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Matullo G, Peluso M, Polidoro S, Guarrera S, Munnia A, Krogh V, et al. Combination of DNA repair gene single nucleotide polymorphisms and increased levels of DNA adducts in a population-based study. Cancer Epidemiol Biomark Prev. 2003;12:674–7.Google Scholar
  31. 31.
    Xin Y, Hao S, Lu J, Wang Q, Zhang L. Association of ercc1 c8092a and ercc2 lys751gln polymorphisms with the risk of glioma: a meta-analysis. PLoS One. 2014;9:e95966.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Ni M, Zhang W-z, Qiu J-r, Liu F, Li M, Zhang Y-j, Liu Q, Bai J: Association of ercc1 and ercc2 polymorphisms with colorectal cancer risk in a Chinese population. Scientific reports 2014; 4Google Scholar
  33. 33.
    Uemura S, Kuramochi H, Higuchi R, Nakajima G, Yamamoto M: Ercc1 mRNA expression as a postoperative prognostic marker in extrahepatic bile duct cancer. Annals of surgical oncology 2014:1–7.Google Scholar
  34. 34.
    Koeppel F, Poindessous V, Lazar V, Raymond E, Sarasin A, Larsen AK. Irofulven cytotoxicity depends on transcription-coupled nucleotide excision repair and is correlated with xpg expression in solid tumor cells. Clin Cancer Res. 2004;10:5604–13.CrossRefPubMedGoogle Scholar
  35. 35.
    Zhao YL, Yang LB, Geng XL, Zhou QL, Qin H, Yang L, et al. The association of xpg and mms19l polymorphisms response to chemotherapy in osteosarcoma. Pakistan journal of medical sciences. 2013;29:1225–9.PubMedPubMedCentralGoogle Scholar
  36. 36.
    Hatfield MD, Reis AM, Obeso D, Cook JR, Thompson DM, Rao M, et al. Identification of mms19 domains with distinct functions in NER and transcription. DNA Repair (Amst). 2006;5:914–24.CrossRefGoogle Scholar
  37. 37.
    Thornton A, Lee P. Publication bias in meta-analysis: its causes and consequences. J Clin Epidemiol. 2000;53:207–16.CrossRefPubMedGoogle Scholar
  38. 38.
    Poynard T, Conn HO. The retrieval of randomized clinical trials in liver disease from the medical literature: a comparison of medlars and manual methods. Control Clin Trials. 1985;6:271–9.CrossRefPubMedGoogle Scholar
  39. 39.
    Ottaviani G, Jaffe N. The epidemiology of osteosarcoma. Cancer Treat Res. 2009;152:3–13.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Jinsong Li
    • 1
  • Shaohua Liu
    • 2
  • Weiguo Wang
    • 1
  • Kexiang Zhang
    • 1
  • Zhendong Liu
    • 1
  • Chaoyue Zhang
    • 1
  • Shijie Chen
    • 1
  • Song Wu
    • 1
  1. 1.Department of OrthopaedicsThe Third Xiangya Hospital of Central South UniversityChangshaChina
  2. 2.Department of Spine SurgeryThe Xiangya Hospital of Central South UniversityChangshaChina

Personalised recommendations