Goretti Duran1,2, Santiago Aguín3,4, Raquel Cruz5, Francisco Barros6, José María Giráldez1,2, Beatriz Bernárdez1,2, Rafael López-López3,4, Ángel Carracedo6,7,8, María Jesús Lamas1,2. 1. Pharmacy Department, University Hospital of Santiago (SERGAS), Santiago de Compostela, Spain. 2. Clinical Pharmacology Group, Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain. 3. Translational Medical Oncology, Health Research Institute of Santiago (IDIS), University Hospital of Santiago (SERGAS), Santiago de Compostela, Spain. 4. Liquid Biopsy Analysis Unit, Health Research Institute of Santiago (IDIS), University Hospital of Santiago (SERGAS), Santiago de Compostela, Spain. 5. Center for Biomedical Research on Rare Diseases (CIBERER), Genomics Medicine Group, CIMUS, University of Santiago de Compostela, Santiago de Compostela, Spain. 6. Grupo de Medicina Xenómica, CIBERER, Fundación Pública Galega de Medicina Xenómica - SERGAS, Santiago de Compostela, Spain. 7. Grupo de Medicina Xenómica, Universidade de Santiago de Compostela, Centro Nacional de Genotipado - Plataforma de Recursos Biomoleculares y Bioinformáticos - Instituto de Salud Carlos III (CeGen-PRB2-ISCIII), Santiago de Compostela, Spain. 8. Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia.
Abstract
BACKGROUND: Platinum-based chemoradiotherapy (CRT) is the standard treatment for locally advanced head and neck squamous-cell carcinomas (HNSCC), and most patients experience serious toxicities. The aim of this study was to investigate the association between candidate genes involved in radiation/platinum pathways and acute toxicity of CRT to determine the predictive value of these polymorphisms for toxicity. METHODS: Thirty-six selected single nucleotide polymorphisms (SNPs) in 29 genes were genotyped in 110 patients treated with cisplatin-based CRT. DNA was obtained from blood samples, and SNP analysis was performed using a MassARRAY iPLEX Gold (Sequenom) method. RESULTS: Patients with ERCC1 rs11615-C allele (P = .0066), ERCC1 rs735482-C allele (P = .0204), and ERCC4 rs1799801-C allele (P = .0286) had lower risk of grade 2-3 hematologic toxicity. In addition, the presence of G allele of GSTP1 was associated with a significantly lower risk of severe dysphagia (P = .0004). CONCLUSION: Polymorphisms in ERCC1 and GSTP1 may act as prognostic factors of acute toxicity during treatment with CRT in HNSCC patients.
BACKGROUND:Platinum-based chemoradiotherapy (CRT) is the standard treatment for locally advanced head and neck squamous-cell carcinomas (HNSCC), and most patients experience serious toxicities. The aim of this study was to investigate the association between candidate genes involved in radiation/platinum pathways and acute toxicity of CRT to determine the predictive value of these polymorphisms for toxicity. METHODS: Thirty-six selected single nucleotide polymorphisms (SNPs) in 29 genes were genotyped in 110 patients treated with cisplatin-based CRT. DNA was obtained from blood samples, and SNP analysis was performed using a MassARRAY iPLEX Gold (Sequenom) method. RESULTS:Patients with ERCC1rs11615-C allele (P = .0066), ERCC1rs735482-C allele (P = .0204), and ERCC4rs1799801-C allele (P = .0286) had lower risk of grade 2-3 hematologic toxicity. In addition, the presence of G allele of GSTP1 was associated with a significantly lower risk of severe dysphagia (P = .0004). CONCLUSION: Polymorphisms in ERCC1 and GSTP1 may act as prognostic factors of acute toxicity during treatment with CRT in HNSCCpatients.
Authors: Goretti Duran; Raquel Cruz; Santiago Aguín; Francisco Barros; José María Giráldez; Beatriz Bernárdez; Irene Zarra; Rafael López-López; Ángel Carracedo; María Jesús Lamas Journal: Cancer Chemother Pharmacol Date: 2021-07-26 Impact factor: 3.333