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´gueret 2 and Jacques Robert 1 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, Hoˆ pital 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 chemo- therapy 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 platinum-based chemotherapy, especially those involving the nucleotide excision repair (NER) pathway. [5,6] Platinum compounds form covalent DNA adducts, mainly with the N 7 atom of guanine. This results in a distortion of the DNA helix and blocks DNA replication, leading eventually to cell apoptosis. NER is able to repair several types of DNA damage, including platinum adducts and UV-induced lesions. It consists of a multiprotein complex containing several ex- cision repair cross-complementation group (ERCC) proteins – in particular, two endonucleases (ERCC1 and ERCC5/XPG) and a helicase (ERCC2/XPD), which are associated with the transcription factor IIH complex, along with other proteins. [6] ORIGINAL RESEARCH ARTICLE 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.