T Powrózek1, R Mlak2, P Krawczyk3, I Homa3, M Ciesielka4, P Kozioł4, M Prendecka2, J Milanowski3, T Małecka-Massalska2. 1. Department of Pneumology, Oncology and Allergology, Medical University of Lublin, Jaczewskiego 8, 20-954, Lublin, Poland. tomaszpowrozek@gmail.com. 2. Department of Human Physiology, Medical University of Lublin, Radziwiłłowska 11, 20-080, Lublin, Poland. 3. Department of Pneumology, Oncology and Allergology, Medical University of Lublin, Jaczewskiego 8, 20-954, Lublin, Poland. 4. Department of Forensic Medicine, Medical University of Lublin, Ceramiczna 1, 20-150, Lublin, Poland.
Abstract
INTRODUCTION: Platinum-based chemotherapy and 3rd generation drugs is still the main treatment option for advanced non-small cell lung cancer (NSCLC) patients without activating EGFR mutations or ALK rearrangements. However, the side effects associated with cytostatics are well known. Changes in the genes (e.g. single nucleotide polymorphisms, SNPs) encoding proteins regulating DNA repair or cell division could potentially influence on both the susceptibility of cancer cells to chemotherapy, and the occurrence of toxicities. MATERIALS AND METHODS: In presented study, the relationship between the fourteen SNPs in nine DNA repair and cell division regulating genes: ERCC1, XPD, XPA, XPC, XRCC1, XPG, RRM1, BRCA1, STMN1 and the toxicity of first-line chemotherapy in NSCLC patients were investigated. SNPs were determined by SNaPshot PCR® in DNA isolated from peripheral blood of 55 NSCLC patients treated with platinum compound and vinorelbine. The toxicity of therapy was evaluated according to the Common Toxicity Criteria (CTC) Version 4.03. RESULTS: The odds ratio (OR) of severe haematological toxicity was significantly lower in carriers of the T allele of XRCC1 gene (1196A > G, OR = 0.22, 95 % CI: 0.06-0.82, p = 0.018) and higher in the carriers of the T allele (2704C > A) of XPC gene (OR: 7.50, 95 % CI: 0.89-63.17, p = 0.036) compared to the remaining patients. Risk of severe hepatotoxicity was significantly lower in carriers of the C allele of STMN1 (-2166T > C, OR = 0.09, 95 % CI: 0.01-1.12, p = 0.025) than in patients with T allele of this gene. In carriers of G allele (2251A > C, OR: 0.24, 95 % CI: 0.07-0.81, p = 0.017) and T (934G > A, OR: 0.26, 95 % CI: 0.07-0.90, p = 0.029) of XPD gene, risk of severe nephrotoxicity was significantly lower than in other patients. CONCLUSIONS: Selected SNPs of genes encoding DNA repair enzymes and cell division regulation proteins could be useful biomarkers for prediction of platinum and vinorelbine-based chemotherapy toxicity in patients with advanced NSCLC.
INTRODUCTION:Platinum-based chemotherapy and 3rd generation drugs is still the main treatment option for advanced non-small cell lung cancer (NSCLC) patients without activating EGFR mutations or ALK rearrangements. However, the side effects associated with cytostatics are well known. Changes in the genes (e.g. single nucleotide polymorphisms, SNPs) encoding proteins regulating DNA repair or cell division could potentially influence on both the susceptibility of cancer cells to chemotherapy, and the occurrence of toxicities. MATERIALS AND METHODS: In presented study, the relationship between the fourteen SNPs in nine DNA repair and cell division regulating genes: ERCC1, XPD, XPA, XPC, XRCC1, XPG, RRM1, BRCA1, STMN1 and the toxicity of first-line chemotherapy in NSCLCpatients were investigated. SNPs were determined by SNaPshot PCR® in DNA isolated from peripheral blood of 55 NSCLCpatients treated with platinum compound and vinorelbine. The toxicity of therapy was evaluated according to the Common Toxicity Criteria (CTC) Version 4.03. RESULTS: The odds ratio (OR) of severe haematological toxicity was significantly lower in carriers of the T allele of XRCC1 gene (1196A > G, OR = 0.22, 95 % CI: 0.06-0.82, p = 0.018) and higher in the carriers of the T allele (2704C > A) of XPC gene (OR: 7.50, 95 % CI: 0.89-63.17, p = 0.036) compared to the remaining patients. Risk of severe hepatotoxicity was significantly lower in carriers of the C allele of STMN1 (-2166T > C, OR = 0.09, 95 % CI: 0.01-1.12, p = 0.025) than in patients with T allele of this gene. In carriers of G allele (2251A > C, OR: 0.24, 95 % CI: 0.07-0.81, p = 0.017) and T (934G > A, OR: 0.26, 95 % CI: 0.07-0.90, p = 0.029) of XPD gene, risk of severe nephrotoxicity was significantly lower than in other patients. CONCLUSIONS: Selected SNPs of genes encoding DNA repair enzymes and cell division regulation proteins could be useful biomarkers for prediction of platinum and vinorelbine-based chemotherapy toxicity in patients with advanced NSCLC.
Authors: Amy Murphy; Jen-Hwa Chu; Mousheng Xu; Vincent J Carey; Ross Lazarus; Andy Liu; Stanley J Szefler; Robert Strunk; Karen Demuth; Mario Castro; Nadia N Hansel; Gregory B Diette; Becky M Vonakis; N Franklin Adkinson; Barbara J Klanderman; Jody Senter-Sylvia; John Ziniti; Christoph Lange; Tomi Pastinen; Benjamin A Raby Journal: Hum Mol Genet Date: 2010-09-10 Impact factor: 6.150
Authors: Ivana Sullivan; Juliana Salazar; Margarita Majem; Cinta Pallarés; Elisabeth Del Río; David Páez; Montserrat Baiget; Agustí Barnadas Journal: Cancer Lett Date: 2014-07-25 Impact factor: 8.679
Authors: Rafael Rosell; Giorgio Scagliotti; Kathleen D Danenberg; Reginald V N Lord; Gerold Bepler; Silvia Novello; Janine Cooc; Lucio Crinò; José Javier Sánchez; Miquel Taron; Corrado Boni; Filippo De Marinis; Maurizio Tonato; Maurizio Marangolo; Felice Gozzelino; Franceso Di Costanzo; Massimo Rinaldi; Dennis Salonga; Craig Stephens Journal: Oncogene Date: 2003-06-05 Impact factor: 9.867
Authors: Wenting Wu; Wei Zhang; Rong Qiao; Dan Chen; Huibo Wang; Yi Wang; Shuyu Zhang; Ge Gao; Aiqin Gu; Jie Shen; Ji Qian; Weiwei Fan; Li Jin; Baohui Han; Daru Lu Journal: Clin Cancer Res Date: 2009-05-19 Impact factor: 12.531
Authors: Anke H Maitland-van der Zee; Bruce C Carleton; Zulfan Zazuli; Catharina J P Op 't Hoog; Susanne J H Vijverberg; Rosalinde Masereeuw; Shahrad Rod Rassekh; Mara Medeiros; Rodolfo Rivas-Ruiz Journal: Pediatr Nephrol Date: 2022-06-24 Impact factor: 3.714
Authors: Jun Gong; May Cho; Rohan Gupta; Timothy W Synold; Paul Frankel; Christopher Ruel; Marwan Fakih; Vincent Chung; Dean Lim; Joseph Chao Journal: Oncologist Date: 2019-02-01
Authors: Marije J Klumpers; Ward De Witte; Giovanna Gattuso; Elisabetta Schiavello; Monica Terenziani; Maura Massimino; Corrie E M Gidding; Sita H Vermeulen; Chantal M Driessen; Carla M Van Herpen; Esther Van Meerten; Henk-Jan Guchelaar; Marieke J H Coenen; D Maroeska W M Te Loo Journal: J Pers Med Date: 2022-05-28