Skip to main content

Advertisement

SpringerLink
Log in

Genetic polymorphism of GSTP1 and ERCC1 correlated with response to platinum-based chemotherapy in non-small cell lung cancer

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

Abstract

The study aims to investigate whether the glutathione S transferase P1 (GSTP1) and excision repair cross-complementing group 1 (ERCC1) polymorphism influence the response to treatment with platinum-based chemotherapy in Chinese patients with non-small cell lung cancer. Ninety-one patients with metastatic non-small lung cancer were evaluated. Blood samples were obtained from each patient before chemotherapy. They are all administered modified TP, GP, NP regimens. Curative effects in patients were evaluated after at least two cycles of treatment. TTP was calculated. The response rate of GSTP1 with G/G + G/A group and A/A group is 54.55 % (24/44) and 21.28 % (10/47) (P = 0.001), respectively. The response rate of ERCC1 with C/C group and C/T + T/T group is 51.11 % (23/45) and 23.91 % (11/46) (P = 0.007), respectively. Patients with both G/G + G/A and C/C has the response rate of 64.52 % (20/31) (P = 0.000). Logistic regression analysis shows a significant increased chance of treatment response in patients with G/G + G/A genotype versus A/A genotype (P = 0.008) and with T/T + C/T genotype versus C/C genotype (P = 0.001). The median TTP of all patients is 7.32 months. The TTP of individuals with G/G + G/A genotype is 9.56 months, and those with A/A genotype had an TTP of 5.23 months. The TTP of individuals with C/C genotype is 9.16 months, and those with T/T + C/T genotype is 5.53 months. Kaplan–Meier analysis shows that ERCC1 and GSTP1 polymorphisms are correlated with TTP. The log-rank test is was marginally significant (P < 0.01). GSTP1 and ERCC1 polymorphism are correlated with response to platinum-based chemotherapy and have prognostic value for TTP.

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

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. American Cancer Society. Cancer facts and figures 2013. Atlanta, Ga, USA: American Cancer Society; 2013. http://www.cancer.org/acs/groups/content/@epidemiologysurveilance/documents/document/acspc-036845.pdf.

  2. American Cancer Society. Non-small cell lung cancer; 2013. http://www.cancer.org/cancer/lungcancer-non-smallcell/index.

  3. Mok TS, Wu Y-L, Thongprasert S, et al. Gefitinib or carboplatin–paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009;361:947–57.

    Article  CAS  PubMed  Google Scholar 

  4. Dancey JE, Dobbin KK, Groshen S, et al. Guidelines for the development and incorporation of biomarker studies in early clinical trials of novel agents. Clin Cancer Res. 2010;16:1745–55.

    Article  CAS  PubMed  Google Scholar 

  5. Xu J, Yin Z, Shen H, et al. A genetic polymorphism in pre-miR-27a confers clinical outcome of non-small cell lung cancer in a Chinese population. PLoS One. 2013;8:e79135.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  6. Okano Y, Nezu U, Enokida Y, et al. SNP (–617C>A) in ARE-like loci of the NRF2 gene: a new biomarker for prognosis of lung adenocarcinoma in Japanese non-smoking women. PLoS One. 2013;8:e73794.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. Ding C, Li C, Wang H, Li B, Guo Z. A miR-SNP of the XPO5 gene is associated with advanced non-small-cell lung cancer. Onco Targets Ther. 2013;6:877.

    CAS  PubMed Central  PubMed  Google Scholar 

  8. Shitara M, Sasaki H, Yokota K, et al. Polymorphisms in intron 1 of the EGFR gene in non-small cell lung cancer patients. Exp Ther Med. 2012;4:785–9.

    CAS  PubMed Central  PubMed  Google Scholar 

  9. Jung M, Cho BC, Lee CH, et al. EGFR polymorphism as a predictor of clinical outcome in advanced lung cancer patients treated with EGFR-TKI. Yonsei Med J. 2012;53:1128–35.

    Article  PubMed Central  PubMed  Google Scholar 

  10. Gonlugur U, Pinarbasi H, Gonlugur TE, Silig Y. The association between polymorphisms in glutathione S-transferase (GSTM1 and GSTT1) and lung cancer outcome. Cancer Invest. 2006;24:497–501.

    Article  CAS  PubMed  Google Scholar 

  11. Peklak-Scott C, Smitherman PK, Townsend AJ, Morrow CS. Role of glutathione S-transferase P1-1 in the cellular detoxification of cisplatin. Mol Cancer Ther. 2008;7:3247–55.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Medeiros R, Vasconcelos A, Costa S, et al. Metabolic susceptibility genes and prostate cancer risk in a southern European population: the role of glutathione S-transferases GSTM1, GSTM3, and GSTT1 genetic polymorphisms. Prostate. 2004;58:414–20.

    Article  CAS  PubMed  Google Scholar 

  13. Sekine I, Minna JD, Nishio K, Tamura T, Saijo N. A literature review of molecular markers predictive of clinical response to cytotoxic chemotherapy in patients with lung cancer. J Thorac Oncol. 2006;1:31–7.

    Article  PubMed  Google Scholar 

  14. Breen D, Barlési F. The place of excision repair cross complementation 1 (ERCC1) in surgically treated non-small cell lung cancer. Eur J Cardiothorac Surg. 2008;33:805–11.

    Article  PubMed  Google Scholar 

  15. Zhu C-Q, Ding K, Strumpf D, et al. Prognostic and predictive gene signature for adjuvant chemotherapy in resected non-small-cell lung cancer. J Clin Oncol. 2010;28:4417–24.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. London SJ, Yuan J-M, Chung F-L, et al. Isothiocyanates, glutathione S-transferase M1 and T1 polymorphisms, and lung-cancer risk: a prospective study of men in Shanghai, China. Lancet. 2000;356:724–9.

    Article  CAS  PubMed  Google Scholar 

  17. Curran JE, Weinstein SR, Griffiths LR. Polymorphisms of glutathione S-transferase genes (GSTM1, GSTP1 and GSTT1) and breast cancer susceptibility. Cancer Lett. 2000;153:113–20.

    Article  CAS  PubMed  Google Scholar 

  18. Howells R, Holland T, Dhar K, et al. Glutathione S-transferase GSTM1 and GSTT1 genotypes in ovarian cancer: association with p53 expression and survival. Int J Gynecol Cancer. 2001;11:107–12.

    Article  CAS  PubMed  Google Scholar 

  19. Lizard-Nacol S, Coudert B, Colosetti P, Riedinger J-M, Fargeot P, Brunet-Lecomte P. Glutathione S-transferase M1 null genotype: lack of association with tumour characteristics and survival in advanced breast cancer. Breast Cancer Res. 1999;1:81.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. Allan JM, Wild CP, Rollinson S, et al. Polymorphism in glutathione S-transferase P1 is associated with susceptibility to chemotherapy-induced leukemia. Proc Natl Acad Sci USA. 2001;98:11592–7.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  21. Ada A, Hancer F, Bilgen S, et al. CYP and GST polymorphisms and survival in advanced non-small cell lung cancer patients. Neoplasma. 2010;57:512.

    Article  CAS  PubMed  Google Scholar 

  22. Kalikaki A, Kanaki M, Vassalou H, et al. DNA repair gene polymorphisms predict favorable clinical outcome in advanced non-small-cell lung cancer. Clin Lung Cancer. 2009;10:118–23.

    Article  CAS  PubMed  Google Scholar 

  23. Sun N, Sun X, Chen B, et al. MRP2 and GSTP1 polymorphisms and chemotherapy response in advanced non-small cell lung cancer. Cancer Chemother Pharmacol. 2010;65:437–46.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  24. Xu C, Feng D, Li L, et al. The expression and prognostic significance of ERCC1 and GST-pi in lung cancer. Chin J Lung Cancer. 2010;13(3):195–200.

    Google Scholar 

  25. Zhou F, Yu Z, Jiang T, Lv H, Yao R, Liang J. Genetic polymorphisms of GSTP1 and XRCC1: prediction of clinical outcome of platinum-based chemotherapy in advanced non-small cell lung cancer (NSCLC) patients. Age. 2011;60:75.

    Google Scholar 

  26. Li X-D, Han J-C, Zhang Y-J, Li H-B, Wu X-Y. Common variations of DNA repair genes are associated with response to platinum-based chemotherapy in NSCLCs. Asian Pac J Cancer Prev. 2013;14:145–8.

    Article  PubMed  Google Scholar 

  27. Tepeli E, Caner V, Büyükpınarbaşılı N, et al. Expression of ERCC1 and its clinicopathological correlations in non-small cell lung cancer. Mol Biol Rep. 2012;39:335–41.

    Article  CAS  PubMed  Google Scholar 

  28. Zheng Z, Chen T, Li X, Haura E, Sharma A, Bepler G. DNA synthesis and repair genes RRM1 and ERCC1 in lung cancer. N Engl J Med. 2007;356:800–8.

    Article  CAS  PubMed  Google Scholar 

  29. Olaussen KA, Dunant A, Fouret P, et al. DNA repair by ERCC1 in non–small-cell lung cancer and cisplatin-based adjuvant chemotherapy. N Engl J Med. 2006;355:983–91.

    Article  CAS  PubMed  Google Scholar 

  30. Lord RV, Brabender J, Gandara D, et al. Low ERCC1 expression correlates with prolonged survival after cisplatin plus gemcitabine chemotherapy in non-small cell lung cancer. Clin Cancer Res. 2002;8:2286–91.

    CAS  PubMed  Google Scholar 

  31. Roth JA, Carlson JJ. Prognostic role of ERCC1 in advanced non-small-cell lung cancer: a systematic review and meta-analysis. Clin Lung Cancer. 2011;12:393–401.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  32. Cobo M, Isla D, Massuti B, et al. Customizing cisplatin based on quantitative excision repair cross-complementing 1 mRNA expression: a phase III trial in non-small-cell lung cancer. J Clin Oncol. 2007;25:2747–54.

    Article  CAS  PubMed  Google Scholar 

  33. Simon GR, Sharma S, Cantor A, Smith P, Bepler G. ERCC1 expression is a predictor of survival in resected patients with non-small cell lung cancer. CHEST J. 2005;127:978–83.

    Article  Google Scholar 

  34. Choi C, Yang S, Jo H, et al. Proteins involved in DNA damage response pathways and survival of stage I non-small-cell lung cancer patients. Ann Oncol. 2012;23:2088–93.

    Article  CAS  PubMed  Google Scholar 

  35. Seyhan EC, Altın S, Çetinkaya E, et al. Prognostic significance of ERCC1 expression in resected non small cell lung carcinoma. Ann Thorac Cardiovasc Surg. 2011;17:110–7.

    Article  PubMed  Google Scholar 

  36. Olaussen KA, Dunant A, Fouret P, et al. DNA repair by ERCC1 in non-small-cell lung cancer and cisplatin-based adjuvant chemotherapy. N Engl J Med. 2006;355:983–91.

    Article  CAS  PubMed  Google Scholar 

  37. Tseden-Ish M, Choi YD, Cho HJ, et al. Disease-free survival of patients after surgical resection of non-small cell lung carcinoma and correlation with excision repair cross-complementation group 1 expression and genotype. Respirology. 2012;17:127–33.

    Article  PubMed  Google Scholar 

  38. Lee K-H, Min HS, Han S-W, et al. ERCC1 expression by immunohistochemistry and EGFR mutations in resected non-small cell lung cancer. Lung Cancer. 2008;60:401–7.

    Article  PubMed  Google Scholar 

  39. Vilmar AC, Santoni-Rugiu E, Sørensen J. ERCC1 and histopathology in advanced NSCLC patients randomized in a large multicenter phase III trial. Ann Oncol. 2010;21:1817–24.

    Article  CAS  PubMed  Google Scholar 

  40. Wang X, Zhao J, Yang L, et al. Positive expression of ERCC1 predicts a poorer platinum-based treatment outcome in Chinese patients with advanced non-small-cell lung cancer. Med Oncol. 2010;27:484–90.

    Article  CAS  PubMed  Google Scholar 

  41. Holm B, Mellemgaard A, Skov T, Skov BG. Different impact of excision repair cross-complementation group 1 on survival in male and female patients with inoperable non–small-cell lung cancer treated with carboplatin and gemcitabine. J Clin Oncol. 2009;27:4254–9.

    Article  CAS  PubMed  Google Scholar 

  42. Hubner RA, Riley RD, Billingham LJ, Popat S. Excision repair cross-complementation group 1 (ERCC1) status and lung cancer outcomes: a meta-analysis of published studies and recommendations. PLoS One. 2011;6:e25164.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  43. Chen S, Zhang J, Wang R, Luo X, Chen H. The platinum-based treatments for advanced non-small cell lung cancer, is low/negative ERCC1 expression better than high/positive ERCC1 expression? A meta-analysis. Lung Cancer. 2010;70:63–70.

    Article  PubMed  Google Scholar 

  44. Reynolds C, Obasaju C, Schell MJ, et al. Randomized phase III trial of gemcitabine-based chemotherapy with in situ RRM1 and ERCC1 protein levels for response prediction in non–small-cell lung cancer. J Clin Oncol. 2009;27:5808–15.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  45. Zhang S, Li Q, Zhang Q. Expression of ERCC1 and class III β-tubulin in resected non-small cell lung cancer and its correlation with platinum-based adjuvant chemotherapy. Int J Biol Markers. 2010;25:141–9.

    CAS  PubMed  Google Scholar 

  46. Bepler G, Olaussen KA, Vataire A-L, et al. ERCC1 and RRM1 in the international adjuvant lung trial by automated quantitative in situ analysis. Am J Pathol. 2011;178:69–78.

    Article  PubMed Central  PubMed  Google Scholar 

  47. Booton R, Ward T, Ashcroft L, Morris J, Heighway J, Thatcher N. ERCC1 mRNA expression is not associated with response and survival after platinum-based chemotherapy regimens in advanced non-small cell lung cancer. J Thorac Oncol. 2007;2:902–6.

    Article  PubMed  Google Scholar 

  48. Ota S, Ishii G, Goto K, et al. Immunohistochemical expression of BCRP and ERCC1 in biopsy specimen predicts survival in advanced non-small-cell lung cancer treated with cisplatin-based chemotherapy. Lung Cancer. 2009;64:98–104.

    Article  PubMed  Google Scholar 

  49. Friboulet L, Olaussen KA, Pignon J-P, et al. ERCC1 isoform expression and DNA repair in non-small-cell lung cancer. N Engl J Med. 2013;368:1101–10.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  50. Vollebergh MA, Kappers I, Klomp HM, et al. Ligands of epidermal growth factor receptor and the insulin-like growth factor family as serum biomarkers for response to epidermal growth factor receptor inhibitors in patients with advanced non-small cell lung cancer. J Thorac Oncol. 2010;5:1939–48.

    Article  PubMed  Google Scholar 

  51. Zalcman G, Levallet G, Bergot E, et al. Evaluation of class III beta-tubulin (bTubIII) expression as a prognostic marker in patients with resectable non-small cell lung cancer (NSCLC) treated by perioperative chemotherapy (CT) in the phase III trial IFCT-0002. J Clin Oncol. 2009;27:7526.

    Google Scholar 

  52. Herbst R, Blumenschein G Jr, Kim E, et al. Sorafenib treatment efficacy and KRAS biomarker status in the biomarker-integrated approaches of targeted therapy for lung cancer elimination (BATTLE) trial. J Clin Oncol. 2010;28:7609.

    Google Scholar 

  53. Shepherd FA, Tsao M-S. Epidermal growth factor receptor biomarkers in non-small-cell lung cancer: a riddle, wrapped in a mystery, inside an enigma. J Clin Oncol. 2010;28:903–5.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by Medical and health science and technology development plan called The molecular mechanism of DNA damage and repair capacity influenced by XRCC1-399 ERCC1-118 genetic polymorphism. The project number is 2011HZ028.

Conflict of interest

The authors report no conflict of interest in this work.

Author information

Authors and Affiliations

  1. Department of Oncology, Affiliated Hospital of Qingdao University, Qingdao, 266003, People’s Republic of China

    Hongying Lv, Ting Han, Xiaoli Shi, Yasai Yao, Wensheng Qiu, Lu Yue & Jun Liang

  2. Department of Central Experiment, Affiliated Hospital of Qingdao University, Qingdao, 266003, People’s Republic of China

    Yongru Yao

Authors
  1. Hongying Lv
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ting Han
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xiaoli Shi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yasai Yao
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yongru Yao
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Wensheng Qiu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Lu Yue
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jun Liang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jun Liang.

Additional information

Hongying Lv and Ting Han have contributed equally to this work and should be considered co-first authors.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lv, H., Han, T., Shi, X. et al. Genetic polymorphism of GSTP1 and ERCC1 correlated with response to platinum-based chemotherapy in non-small cell lung cancer. Med Oncol 31, 86 (2014). https://doi.org/10.1007/s12032-014-0086-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12032-014-0086-5

Keywords

Search

Navigation