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Tumor Biology

, Volume 35, Issue 5, pp 4023–4029 | Cite as

Role of ERCC1 variants in response to chemotherapy and clinical outcome of advanced non-small cell lung cancer

  • Shao-jun Huang
  • Yu-fei Wang
  • Zhi-yong Jin
  • Jia-yang Sun
  • Zhan-lin Guo
Research Article

Abstract

Excision repair cross-complementation group 1 (ERCC1) and xeroderma pigmentosum-F (XPF) in the nucleotide excision repair pathway have been effectively repairing DNA damage induced by chemotherapeutic agents. We conducted a cohort study to assess the associations of ERCC1 and XPF polymorphisms with response to platinum-based chemotherapy and clinical outcome of non-small-cell lung cancer (NSCLC). One hundred eighty-seven NSCLC cases treated with platinum-based chemotherapy were prospectively analyzed. The predictive value of four SNPs in ERCC1 and two SNPs in XPF in patient's response and survival related to platinum-based chemotherapy were analyzed using χ 2 tests, Kaplan-Meier method, log-rank test, and Cox proportional hazards regression. The overall chemotherapy response rate for treatment was 51.18 %. One hundred eighty-seven patients were followed up, and the median survival time is 17.6 months (ranged from 1 to 50 months). A total of 106 patients (56.68 %) died from NSCLC during the follow-up period. Carriers of the rs3212986 AA and A allele had a borderline significantly lower response rate to the chemotherapy. In the Cox proportional hazards model, patients carrying the ERCC1 rs3212986 AA genotype were significantly associated with increased risk of death from NSCLC when compared with those with CC genotype as a reference variable. This study reported that variants in ERCC1 can be used as a prognostic maker to platinum-based chemotherapy in NSCLC patients.

Keywords

ERCC1 XPF Polymorphism Response Non-small cell lung cancer Chemotherapy Clinical outcome 

Notes

Acknowledgments

This study was supported by a grant from The Affiliated Hospital of Inner Mongolia Medical University.

Conflicts of interest

None.

References

  1. 1.
    International Agency for Research on Cancer (2008). Lung cancer incidence, mortality and prevalence worldwide in 2008. http://globocan.iarc.fr/factsheet.asp. Accessed 8 Jul 2013
  2. 2.
    Molina JR, Yang P, Cassivi SD, et al. Non-small cell lung cancer: epidemiology, risk factors, treatment, and survivorship. Mayo Clin Proc. 2008;83:584–94.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Siegel R, Naishadham D, Jemal A. Cancer statistics. CA Cancer J Clin. 2012;62:10–29.CrossRefPubMedGoogle Scholar
  4. 4.
    Goffin J, Lacchetti C, Ellis PM, Ung YC, Evans WK. First-line systemic chemother-apy in the treatment of advanced non-small cell lung cancer: a systematic review. J Thorac Oncol. 2010;5:260–74.CrossRefPubMedGoogle Scholar
  5. 5.
    Takenaka T, Yano T, Kiyohara C, Miura N, Kouso H, Ohba T, et al. Effects of excision repair cross-complementation group 1 (ERCC1) single nucleotide polymorphisms on the prognosis of non-small cell lung cancer patients. Lung Cancer. 2010;67(1):101–7.CrossRefPubMedGoogle Scholar
  6. 6.
    Friedberg EC. How nucleotide excision repair protects against cancer. Nat Rev Cancer. 2001;1(1):22–33.CrossRefPubMedGoogle Scholar
  7. 7.
    Hoeijmakers JH. Genome maintenance mechanisms for preventing cancer. Nature. 2001;411(6835):366–74.CrossRefPubMedGoogle Scholar
  8. 8.
    Reed E. Platinum-DNA adduct, nucleotide excision repair and platinum based anti-cancer chemotherapy. Cancer Treat Rev. 1998;24(5):331–44.CrossRefPubMedGoogle Scholar
  9. 9.
    Laura JN, Nikhil B, Richard DW. ERCC1 and non-small-cell lung cancer. N Engl J Med. 2007;356:2538–41.CrossRefGoogle Scholar
  10. 10.
    Sijbers AM, de Laat WL, Ariza RR, Biggerstaff M, Wei YF, et al. Xeroderma pigmentosum group F caused by a defect in a structure-specific DNA repair endonuclease. Cell. 1996;86:811–22.CrossRefPubMedGoogle Scholar
  11. 11.
    Chu H, Gu D, Xu M, Xu Z, Gong Y, Gong W, et al. A genetic variant in ERCC2 is associated with gastric cancer prognosis in a Chinese population. Mutagenesis. 2013;28(4):441–6.CrossRefPubMedGoogle Scholar
  12. 12.
    Rumiato E, Cavallin F, Boldrin E, Cagol M, Alfieri R, Basso D. ERCC1 C8092A (rs3212986) polymorphism as a predictive marker in esophageal cancer patients treated with cisplatin/5-FU-based neoadjuvant therapy. Pharmacogenet Genomics. 2013.Google Scholar
  13. 13.
    Biason P, Hattinger CM, Innocenti F, Talamini R, Alberghini M, Scotlandi K, et al. Nucleotide excision repair gene variants and association with survival in osteosarcoma patients. Pharmacogenomics J. 2012;12(6):476–83.CrossRefPubMedGoogle Scholar
  14. 14.
    Mathiaux J, Le Morvan V, Pulido M, Jougon J, Bégueret H, Robert J. Role of DNA repair gene polymorphisms in the efficiency of platinum-based adjuvant chemotherapy for non-small cell lung cancer. Mol Diagn Ther. 2011;15(3):159–66.CrossRefPubMedGoogle Scholar
  15. 15.
    Dong J, Hu Z, Shu Y, Pan S, Chen W, Wang Y, et al. Potentially functional polymorphisms in DNA repair genes and non-small-cell lung cancer survival: a pathway-based analysis. Mol Carcinog. 2012;51(7):546–52.CrossRefPubMedGoogle Scholar
  16. 16.
    Li Y, Liu Z, Liu H, Wang LE, Tan D, Ajani JA, et al. ERCC1 and ERCC2 variants predict survival in gastric cancer patients. PLoS One. 2013;8(9):e71994.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Yang Z, Fang X, Pei X, Li H. Polymorphisms in the ERCC1 and XPF genes and risk of breast cancer in a Chinese population. Genet Test Mol Biomarkers. 2013;17(9):700–6.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Mlak R, Krawczyk P, Ramlau R, Kalinka-Warzocha E, Wasylecka-Morawiec M, Wojas-Krawczyk K, et al. Predictive value of ERCC1 and RRM1 gene single-nucleotide polymorphisms for first-line platinum- and gemcitabine-based chemotherapy in non-small cell lung cancer patients. Oncol Rep. 2013;30(5):2385–98.PubMedGoogle Scholar
  19. 19.
    Goode EL, Ulrich MC, Potter JD. Polymorphisms in DNA repair genes and associations with cancer risk. Cancer Epidemiol Biomarkers Prev. 2002;11:1513–30.PubMedGoogle Scholar
  20. 20.
    Spitz MR et al. Modulation of nucleotide excision repair capacity by XPD polymorphisms in lung cancer patients. Cancer Res. 2001;61:1354–7.PubMedGoogle Scholar
  21. 21.
    Oguri T, Mitsuma A, Inada-Inoue M, Morita S, Shibata T, Shimokata T, et al. Genetic polymorphisms associated with oxaliplatin-induced peripheral neurotoxicity in Japanese patients with colorectal cancer. Int J Clin Pharmacol Ther. 2013;51(6):475–81.CrossRefPubMedGoogle Scholar
  22. 22.
    Mazzoni F, Cecere FL, Meoni G, Giuliani C, Boni L, Camerini A. Phase II trial of customized first line chemotherapy according to ERCC1 and RRM1 SNPs in patients with advanced non-small-cell lung cancer. Lung Cancer. 2013.Google Scholar
  23. 23.
    Xu TP, Shen H, Liu LX, Shu YQ. Association of ERCC1-C118T and -C8092A polymorphisms with lung cancer risk and survival of advanced-stage non-small cell lung cancer patients receiving platinum-based chemotherapy: a pooled analysis based on 39 reports. Gene. 2013;526:265–74.CrossRefPubMedGoogle Scholar
  24. 24.
    Zhu XD, Niedernhofer L, Kuster B, Mann M, Hoeijmakers JH, de Lange T. ERCC1/XPF removes the 3′ overhang from uncapped telomeres and represses formation of telomeric DNA-containing double minute chromosomes. Mol Cell. 2003;12:1489–98.CrossRefPubMedGoogle Scholar
  25. 25.
    Kornguth DG, Garden AS, Zheng Y, Dahlstrom KR, Wei Q, Sturgis EM. Gastrostomy in oropharyngeal cancer patients with ERCC4 (XPF) germline variants. Int J Radiat Oncol Biol Phys. 2005;62:665–71.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2013

Authors and Affiliations

  • Shao-jun Huang
    • 1
  • Yu-fei Wang
    • 1
  • Zhi-yong Jin
    • 1
  • Jia-yang Sun
    • 1
  • Zhan-lin Guo
    • 1
  1. 1.Department of Cardiovascular and Thoracic SurgeryThe Affiliated Hospital of Inner Mongolia Medical UniversityHuhhotChina

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