Role of DNA Repair Gene Polymorphisms in the Efficiency of Platinum-Based Adjuvant Chemotherapy for Non-Small Cell Lung
- PDF / 155,512 Bytes
- 8 Pages / 612.28 x 790.87 pts Page_size
- 12 Downloads / 142 Views
Mol Diagn Ther 2011; 15 (3): 159-166 1177-1062/11/0003-0159/$49.95/0
ª 2011 Adis Data Information BV. All rights reserved.
Role of DNA Repair Gene Polymorphisms in the Efficiency of Platinum-Based Adjuvant Chemotherapy for Non-Small Cell Lung Cancer Juliette Mathiaux,1,2 Vale´rie Le Morvan,1 Marina Pulido,3 Jacques Jougon,2 Hugues Be´gueret2 and Jacques Robert1 1 Institut National de la Sante´ et de la Recherche Me´dicale (INSERM) Unite´ 916, Universite´ de Bordeaux, Institut Bergonie´, Bordeaux, France 2 Centre Hospitalier Universitaire de Bordeaux, Hoˆpital du Haut-Le´veˆque, Bordeaux, France 3 INSERM Centre d’Investigation Clinique (CIC)-EC7 et Unite´ de Recherche et d’Epide´miologie Cliniques, Institut Bergonie´, Bordeaux, France
Abstract
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.
Introduction Non-small cell lung cancer (NSCLC) is the leading cause of cancer death in industrialized countries. Most of the patients are diagnosed at locally advanced or disseminated stages. Only a small proportion of patients (around 30%) with early-stage disease can undergo curative surgical resection, but even after complete resection, approximately 30–70% will relapse and die within 5 years as a function of the tumor stage. Since 2004–2005, several randomized studies have confirmed the benefit of post-operative platinum-based adjuvant therapy in NSCLC, with modest absolute improvements in 5-year survival ranging from approximately 5% to 15%.[1-4]
DNA repair mechanisms are important determinants of the sensitivity to plati
Data Loading...