Skip to main content
SpringerLink
Log in

Effect of ERCC1 polymorphisms and the modification by smoking on the survival of non-small cell lung cancer patients

  • Original
  • Published:
Medical Oncology Aims and scope Submit manuscript

Abstract

A few reports for ERCC1 SNPs were conducted in patients treated with cisplatin chemotherapy. The aim of this study is to determine whether the SNPs are a prognostic factor related to the treatment or not and if smoking level of the patients have any relationship to the SNPs' effect on the survival. Peripheral blood lymphocytes of 423 consecutive non-small cell lung cancer patients were examined: 245 of the patients received cisplatin combination chemotherapy and 178 received only conservative care. We examined ERCC1 SNPs (codon 118 C/T and 8092 C/A). Whereas ERCC1 118 SNP had no effect on the survival in patients' given no treatment, an effect of the SNP was observed in the treatment group, especially in stage III. When smoking was considered, the risk effect of the T allele was shown to be significantly associated with the group that had more than 50 pack yr (p=0.03). As for the ERCC1 8092 C/A, no significant effects were observed in the treated group and the non-treatment group. These findings may suggest that the ERCC1 118 SNP is an useful prognostic factor related to cisplatin therapy and the effect of this polymorphism appears to be modified by prognostic factor related to cisplatin therapy and the effect of this polymorphism appears to be modified by smoking.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Paez JG, et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 2004; 304 (5676): 1497–1500.

    Article  PubMed  CAS  Google Scholar 

  2. Lynch TJ, et al. Activating mutations in the epidermal growth factor receptor underlyingresponsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med 2004; 350(21): 2129–2139.

    Article  PubMed  CAS  Google Scholar 

  3. Georgoulias V, et al. Greek Oncology Cooperative Group (GOCG) for Lung Cancer. Platinum based non platinum based chemotherapy in advanced nonsmall cell lung cancer: a randomized multicentre trial. Lancet 2001;357: 1478–1484.

    Article  PubMed  CAS  Google Scholar 

  4. Miller VA, Rigas JR, Grant SC, Pisters KM, Kris MG. New chemotherapeutic agents for non small cell lung cancer. Chest 1995;107 (Suppl 6): 306S-311S.

    PubMed  CAS  Google Scholar 

  5. Schiller JH, et al. Eastein Cooperative Oncology Group. Comparison of four chemotherapy regimens for advanced non small cell lung cancer. N Engl J Med 2002;10 (346): 92–98.

    Article  Google Scholar 

  6. Reed E. Platinum DNA adduct, nucleotide excision repair and platinum based anti-cancer chemotherapy. Cancer Treat Rev 1998;24: 331–344.

    Article  PubMed  CAS  Google Scholar 

  7. Lindahl T, Karran P, Wood RD. DNA excision repair pathways. Curr Opin Genet Dev 1997;7: 158–169.

    Article  PubMed  CAS  Google Scholar 

  8. Li Q, et al. Association between the level of ERCC1 expression and the repair of cisplatin induced DNA damage in human ovarian cancer cells. Anticancer Res 2000;20 (2A): 645–652.

    PubMed  CAS  Google Scholar 

  9. Wei Q, Cheng L., Hong WK, Spitz MR. Reduced DRC in lung cancer patients. Cancer Res 1996;56: 4103–4107.

    PubMed  CAS  Google Scholar 

  10. Metzger R, et al. ERCC1 mRNA levels complement thymidylate synthase, mRNA levels in predicting response and survival for gastric cancer patients receiving combination cisplatin and fluorouracil chemotherapy. J Clin Oncol 1998;16: 309–316.

    PubMed  CAS  Google Scholar 

  11. Ferry KV, Hamilton TC, Johnson SW. Increased nucleotide excision repair in cisplatin resistant ovarian cancer cells: role of ERCC1-XPF. Biochem Pharmacol 2000; 60: 1305–1313.

    Article  PubMed  CAS  Google Scholar 

  12. Britten RA, Liu D, Tessier A, Hutchison MJ, Murray D. ERCC1 expression as a molecular marker of cisplatin resistance in human cervical tumor cells. Int J Cancer 2000;89: 453–457.

    Article  PubMed  CAS  Google Scholar 

  13. Shirota Y, et al. ERCC 1 and thymidylate synthase mRNA levels predict survival for colorectal cancer patients receiving combination oxaliplatin and fluorouracil chemotherapy. J Clin Oncol 2001;19: 4298–4304.

    PubMed  CAS  Google Scholar 

  14. Lord RV, et al. Low ERCC1 expression correlates with prolonged survival after cisplatin plus gemcitabine chemotherapy in non-small cell lung cancer. Clin Cancer Res 2002; 8: 2286–2291.

    PubMed  CAS  Google Scholar 

  15. Sturgis EM, Dahlstrom KR, Spitz MR,Wei Q. DNA repair gene ERCC1 and ERCC2/XPD polymorphisms and risk of squamous cell carcinoma of the head and neck. Arck Otolaryngol Head Neck Surg 2002;128: 1084–1088.

    Google Scholar 

  16. Rosell R, Taron M, O'Brate A. Predictive molecular markers in non small cell lung cancer. Curr Opin Oncol 2001;13: 101–109.

    Article  PubMed  CAS  Google Scholar 

  17. Park DJ, et al. ERCC1 gene polymorphism as a predictor for clinical outcome in advanced colorectal cancer patients treated with platinum based chemotherapy. Clin Adv Hematol Oncol 2003;1: 162–166.

    PubMed  Google Scholar 

  18. Zhou W, et al. Excision repair cross-complementation group 1 polymorphism predicts overall survival in advanced non small cell lung cancer patients treated with platinum based chemotherapy. Clin Cancer Res 2004;10: 4939–4943.

    Article  PubMed  CAS  Google Scholar 

  19. Ryu JS, et al. Association between polymorphisms of ERCC1 and XPD and survival in non-small-cell lung cancer patients treated with cisplatin combination chemotherapy. Lung Cancer 2004;44(3): 311–316.

    Article  PubMed  Google Scholar 

  20. Suk R, et al. Polymorphisms in ERCC1 and grade 3 or 4 toxicity in nonsmall cell lung cancer patients. Clin Cancer Res 2005;11(4): 1534–1538.

    Article  PubMed  CAS  Google Scholar 

  21. Shen MR, Jones IM, Mohrenweiser H. Nonconservative amino acid substitution variants exist at polymorphic frequency in DNA repair genes in healthy humans Cancer Res 1998;58: 604–608.

    PubMed  CAS  Google Scholar 

  22. Chen P, et al. Association of an ERCC1 polymorphism with adult onset glioma. Cancer Epidemiol Biomarkers Prev 2000;9: 843–847.

    PubMed  CAS  Google Scholar 

  23. Zhou W, et al. Gene smoking interaction associations for the ERCC1 polymorphisms in the risk of lung cancer. Cancer Epidemiol Biomarkers Prev 2005;14(2): 491–496.

    Article  PubMed  CAS  Google Scholar 

  24. Salgia R, Skarin AT. Molecular abnormalities in lung cancer. J Clin Oncol 1998;16: 1207–1217.

    PubMed  CAS  Google Scholar 

  25. Greatens TM, et al. Do molecular markers predict survival in non small cell lung cancer? Am J Respir Crit Care Med 1998;157: 1093–1097.

    PubMed  CAS  Google Scholar 

  26. Isla D, et al. Single nucleotide polymorphisms and outcome in docetaxel cisplatin treated advanced non small cell lung cancer. Ann Oncol 2004;15: 1194–1203.

    Article  PubMed  CAS  Google Scholar 

  27. Park JY, et al. Polymorphism of the DNA repair gene XRCC1 and risk of primary lung cancer. Cancer Epidemiol Biomarkers Prev 2002;11: 23–27.

    PubMed  CAS  Google Scholar 

  28. Ito G., et al. Gene environment interactions between the smoking habit and polymorphisms in the DNA repair genes, APE1 Aspl48Glu and XRCC1 Arg399Gln, in Japanese lung cancer risk. Carcinogenesis 2004;25(8): 1395–1401.

    Article  PubMed  CAS  Google Scholar 

  29. Wu X, et al. XPA polymorphism associated with reduced lung cancer risk and a modulating effect on nucleotide excision repair capacity. Carcinogenesis 2003;24(3): 505–509.

    Article  PubMed  CAS  Google Scholar 

  30. Zhou W, et al. Polymorphisms in the DNA Repair Genes XRCC1 and ERCC2, Smoking, and Lung cancer risk. Cancer Epidemiol Biomarkers Prev 2003;12: 359–365.

    PubMed  CAS  Google Scholar 

  31. Butkiewicz D, et al. Association between the risk for lung adenocarcinoma and a (-4) G to A polymorphism in the XPA gene. Cancer Epidemiol Biomarkers Prev 2004;13 (12): 2242–2246.

    PubMed  CAS  Google Scholar 

  32. David-Beabes GL, London SJ. Genetic polymorphism of XRCC1 and lung cancer risk among African Americans and Caucasians. Lung Cancer 2001;34: 333–339.

    Article  PubMed  CAS  Google Scholar 

  33. Terry MB, et al. Polymorphism in the DNA repair gene XPD, polycyclic aromatic hydrocarbon DNA adducts, cigarette smoking, and breast cancer risk. Cancer Epidemiol Biomarkers Prev 2004; 13(12): 2053–2058.

    PubMed  CAS  Google Scholar 

  34. Wei Q, et al. Reduced expression of hMLH1 and hGTBP: a risk factor for head and neck cancer. Cancer Epidemiol Biomarkers Prev 1998;7: 309–314.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Preventive Medicine, College of Medicine, Seoul National University, Seoul, Korea

    So-Yeon Park, Yun-Chul Hong & Jin-Hee Kim

  2. Department of Internal Medicine, College of Medicine, Inha University, Incheon, Korea

    Seung-Min Kwak, Jae-Hwa Cho, Hong-Lyeol Lee & Jeong-Seon Ryu

Authors
  1. So-Yeon Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yun-Chul Hong
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jin-Hee Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Seung-Min Kwak
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jae-Hwa Cho
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hong-Lyeol Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jeong-Seon Ryu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jeong-Seon Ryu.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Park, SY., Hong, YC., Kim, JH. et al. Effect of ERCC1 polymorphisms and the modification by smoking on the survival of non-small cell lung cancer patients. Med Oncol 23, 489–498 (2006). https://doi.org/10.1385/MO:23:4:489

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1385/MO:23:4:489

Key Words

Search

Navigation