Background: Cisplatin-based adjuvant treatment of non-small cell lung cancer (NSCLC) has become standard, thanks to the studies that have shown a significant survival advantage. The identification of patients who could benefit from this adjuvant treatment would allow ineffective and toxic administrations to be avoided. Immunohistochemical expression of the excision repair cross-complementation group (ERCC)-1 protein has been associated with response to platinum-based chemotherapy in patients with NSCLC, and some polymorphisms of the genes involved in DNA repair have been shown to be associated with survival in advanced NSCLC.
Objective: The aim of our study was to evaluate the progression-free survival and tolerability of adjuvant treatment with platinum-based chemotherapy in patients with NSCLC, according to common DNA repair gene polymorphisms and ERCC1 expression.
Methods: We investigated the association of three DNA repair gene polymorphisms — Asn118Asn in ERCC1 (rs11615), Lys751Gln in ERCC2 (rs13181), and Asp1104His in ERCC5 (rs17655) — with the progression-free survival of 85 patients treated with platinum-based chemotherapy after surgery for NSCLC.
Results: We did not find significant associations between any of these polymorphisms and progression-free survival, nor did we observe any difference in progression-free survival according to ERCC1 expression.
Conclusion: The previously reported impact of DNA repair gene polymorphisms on platinum-based chemotherapy treatment of advanced NSCLC was not observed in our study in the adjuvant setting.
We are grateful to the clinicians and pathologists involved in the study — Drs J. Dubrez, C. Klein, and A. Daubech — and to the clinical research assistants. JM received a fellowship from the Institut National du Cancer (Paris, France). This work was funded through INSERM U916 grants.
None of the authors has any conflict of interest to declare.
Arriagada R, Bergman B, Dunant A, et al. Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer. N Engl J Med 2004; 350: 351–60PubMedCrossRefGoogle Scholar
Winton T, Livingston R, Johnson D, et al. Vinorelbine plus cisplatin vs observation in resected non-small-cell lung cancer. N Engl J Med 2005; 352: 2589–97PubMedCrossRefGoogle Scholar
Scagliotti GV, Fossati R, Torri V, et al. Randomized study of adjuvant chemotherapy for completely resected stage I, II, or IIIA non-small-cell lung cancer. J Natl Cancer Inst 2003; 95: 1453–61PubMedCrossRefGoogle Scholar
Douillard JY, Rosell R, De Lena M, et al. Adjuvant vinorelbine plus cisplatin versus observation in patients with completely resected stage IB-IIIA non-small-cell lung cancer (Adjuvant Navelbine International Trialist Association [ANITA]): a randomised controlled trial. Lancet Oncol 2006; 7: 719–27PubMedCrossRefGoogle Scholar
De Laat WL, Jaspers NGJ, Hoeijmakers JH. Molecular mechanism of nucleotide excision repair. Genes Dev 1999; 13: 768–85PubMedCrossRefGoogle Scholar
Bosken CH, Wei Q, Amos CI, et al. An analysis of DNA repair as a determinant of survival in patients with non-small-cell lung cancer. J Natl Cancer Inst 2002; 94: 1091–9PubMedCrossRefGoogle Scholar
Britten A, Liu D, Tessier A, et al. ERCC1 expression as a molecular marker of cisplatin resistance in human cervical tumor cells. Int J Cancer 2000; 89: 453–7PubMedCrossRefGoogle Scholar
Arnould S, Hennebelle I, Canal P, et al. Cellular determinants of oxaliplatin sensitivity in colon cancer cells. Eur J Cancer 2002; 39: 112–9CrossRefGoogle Scholar
Vilmar A, Sorensen JB. Excision repair cross-complementation group 1 in platinum-based treatment of non-small cell lung cancer with special emphasis on carboplatin: a review of current literature. Lung Cancer 2008; 64: 131–9PubMedCrossRefGoogle Scholar
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: 2286–91PubMedGoogle Scholar
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: 983–91PubMedCrossRefGoogle Scholar
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: 2747–54PubMedCrossRefGoogle Scholar
Kiyohara C, Yoshimasu K. Genetic polymorphisms in the nucleotide excision repair pathway and lung cancer risk: a meta-analysis. Int J Med Sci 2007; 4: 59–71PubMedCrossRefGoogle Scholar
Robert J, Le Morvan V, Smith D, et al. Predicting drug response and toxicity based on gene polymorphisms. Crit Rev Oncol Hematol 2005; 54: 171–96PubMedCrossRefGoogle Scholar
Viguier J, Boige V, Miquel C, et al. ERCC1 codon 118 polymorphism is a predictive factor for the tumor response to oxaliplatin/5-fluorouracil combination chemotherapy in patients with advanced colorectal cancer. Clin Cancer Res 2005; 11: 6212–7PubMedCrossRefGoogle Scholar
Isla D, Sarries C, Rosell R, et al. Single nucleotide polymorphisms and outcome in docetaxel-cisplatin-treated advanced non-small-cell lung cancer. Ann Oncol 2004; 15: 1194–203PubMedCrossRefGoogle Scholar
Ryu JS, Hong YC, Han HS, 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: 311–6PubMedCrossRefGoogle Scholar
Kalikaki A, Kanaki M, Vassalou H, et al. DNA repair gene polymorphisms predict favourable clinical outcome in advanced non-small-cell lung cancer. Clin Lung Cancer 2009; 10: 118–23PubMedCrossRefGoogle Scholar
Zhou W, Gurubhagavatula S, Liu G, 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: 4939–43PubMedCrossRefGoogle Scholar
Stoehlmacher J, Park DJ, Zhang W, et al. A multivariate analysis of genomic polymorphisms: prediction of clinical outcome to 5-FU/oxaliplatin combination chemotherapy in refractory colorectal cancer. Br J Cancer 2004; 91: 344–54PubMedGoogle Scholar
Le Morvan V, Smith D, Laurand A, et al. Determination of ERCC2 Lys751Gln and GSTP1 Ile105Val gene polymorphisms in colorectal cancer patients: relationships with treatment outcome. Pharmacogenomics 2007; 8: 1693–703PubMedCrossRefGoogle Scholar
Cui Y, Morgenstern H, Greenland S, et al. Polymorphism of xeroderma pig-mentosum group G and the risk of lung cancer and squamous cell carcinomas of the oropharynx, larynx and oesophagus. Int J Cancer 2006; 118: 714–20PubMedCrossRefGoogle Scholar
Yu JJ, Mu C, Lee KB, et al. A nucleotide polymorphism in ERCC1 in human ovarian cancer cell lines and tumor tissues. Mutat Res 1997; 382: 13–20PubMedCrossRefGoogle Scholar
Arriagada R, Dunant A, Pignon JP, et al. Long-term results of the International Adjuvant Lung Cancer Trial evaluating adjuvant cisplatin-based chemotherapy in resected lung cancer. J Clin Oncol 2010; 28: 35–42PubMedCrossRefGoogle Scholar
Chen S, Zhang J, Wang R, et al. 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: 63–70PubMedCrossRefGoogle Scholar
Bhagwat NR, Roginskaya VY, Acquafondata MB, et al. Immunodetection of DNA repair endonuclease ERCC1-XPF in human tissue. Cancer Res 2009; 69: 6831–8PubMedCrossRefGoogle Scholar
Takebayashi Y, Nakayama K, Kanzaki A, et al. Loss of heterozygosity of nucleotide excision repair factors in sporadic ovarian, colon and lung carcinomas: implication for their roles of carcinogenesis in human solid tumors. Cancer Lett 2001; 174: 115–25PubMedCrossRefGoogle Scholar
Kang CH, Jang BG, Kim DW, et al. Differences in the expression profiles of excision repair crosscomplementation group 1, x-ray repair cross-complementation group 1, and betaIII-tubulin between primary non-small cell lung cancer and metastatic lymph nodes and the significance in mid-term survival. J Thorac Oncol 2009; 4: 1307–12PubMedCrossRefGoogle Scholar
Toffalorio F, Giovannetti E, De Pas T, et al. Expression of gemcitabine- and cisplatin-related genes in non-small-cell lung cancer. Pharmacogenomics J 2010; 10: 180–90PubMedCrossRefGoogle Scholar
Scagliotti GV, Parikh P, von Pawel J, et al. Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer. J Clin Oncol 2008; 26: 3543–51PubMedCrossRefGoogle Scholar
Booton R, Ward T, Heighway J, et al. Xeroderma pigmentosum group D haplotype predicts for response, survival, and toxicity after platinum-based chemotherapy in advanced non-small cell lung cancer. Cancer 2006; 106: 2421–7PubMedCrossRefGoogle Scholar
Suk R, Gurubhagavatula S, Park S, et al. Polymorphisms in ERCC1 and grade 3 or 4 toxicity in non-small cell lung cancer patients. Clin Cancer Res 2005; 11: 1534–8PubMedCrossRefGoogle Scholar
Yin M, Yan J, Voutsina A, et al. No evidence of an association of ERCC1 and ERCC2 polymorphisms with clinical outcomes of platinum-based chemotherapies in non-small cell lung cancer: a meta-analysis. Lung Cancer 2011; 72: 370–7PubMedCrossRefGoogle Scholar