| Autor: |
A. Webb, David Azria, Sarah L. Kerns, Karen Foweraker, Ana Carballo, Barbara Avuzzi, Luis Aznar-Garcia, Roxana Draghici, Monica Ramos, Stéphanie Peeters, Benjamin Gauter-Fleckenstein, Daniel S. Higginson, Anna Maria Paganoni, Ulrich Giesche, Monika Kaushik, Corinne Faivre-Finn, Ananya Choudhury, Andrea Manzoni, Jörg Schäfer, Carsten Herskind, Frances Kenny, Paolo Zunino, Valérie Fonteyne, Abigail Pascoe, S. Morlino, Paloma Sosa-Fajardo, Manjusha Keni, Karin Haustermans, A. Giraldo, Jaroslaw Krupa, Claudia Sangalli, Thomas Schnabel, Gert De Meerleer, Yolande Lievens, Patricia Calvo-Crespo, Marie-Pierre Farcy-Jacquet, Petra Seibold, Nicola Rares Franco, Ramón Lobato-Busto, Irene Fajardo-Paneque, Tim Rattay, Ana Vega, Riccardo Valdagni, Elena Delmastro, Irmgard Helmbold, Ben G. L. Vanneste, Richard G. Stock, Donna Appleton, Debbie Payne, Barry S. Rosenstein, Liv Veldeman, Rebecca Elliott, Tiziana Rancati, Alison M. Dunning, Claire P. Esler, Sridhar Thiagarajan, Elisabetta Garibaldi, Muriel Brengues, Michela Carlotta Massi, Simon Pilgrim, Maria C. De Santis, Wilfried De Neve, Miguel E. Aguado-Barrera, Evert J. Van Limbergen, Olivia-Fuentes-Rios, Paul Symonds, Jenny Chang-Claude, Elena Sperk, Catharine M L West, Petra Stegmaier, Antonio Gómez-Caamaño, Marzia Franceschini, Laura Torrado Moya, Simon Wright, Kufre Sampson, Kalliope Valassiadou, Francesca Ieva, Burkhard Neu, Isabel Dominguez-Rios, Francoise Bons, Marie-Luise Sautter-Bihl, Gilles Defraene, Tommaso Giandini, Meritxel Molla, Sheryl Green, Victoria Harrop, Alessandro Cicchetti, Christian Weiß, Caroline Weltens, Gabriele Pietro, Christopher Kent, Michael Ehmann, Paula Peleteiro, Dirk De Ruysscher, Thomas Blaschke, Ion Bioangiu, Hazem Khout, Samuel Lavers, Ahmed Osman, Laura Fachal, Subramaniam Vasanthan, Marc van Eijkeren, Laura Lozza, Céline Bourgier, Kelly Lambert, Johannes Claßen, Piet Ost, Kerstie Johnson, Christian Weißenberger, Bibiana Piqué-Leiva, Timothy H Ward, Christel Monten, Maarten Lambrecht, Marlon R. Veldwijk, Erik van Limberghen, Kiran Kancherla, Christopher J. Talbot, Barbara Noris Chiorda, Erik Briers, Sheila Shokuhi |
| Přispěvatelé: |
RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, Radiotherapie |
| Jazyk: |
angličtina |
| Rok vydání: |
2021 |
| Předmět: |
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| Zdroj: |
RADIOTHERAPY AND ONCOLOGY
Radiotherapy and Oncology, 159, 241-248. Elsevier Ireland Ltd |
| ISSN: |
0167-8140
1879-0887 |
| Popis: |
AIM: To identify the effect of single nucleotide polymorphism (SNP) interactions on the risk of toxicity following radiotherapy (RT) for prostate cancer (PCa) and propose a new method for polygenic risk score incorporating SNP-SNP interactions (PRSi). MATERIALS AND METHODS: Analysis included the REQUITE PCa cohort that received external beam RT and was followed for 2 years. Late toxicity endpoints were: rectal bleeding, urinary frequency, haematuria, nocturia, decreased urinary stream. Among 43 literature-identified SNPs, the 30% most strongly associated with each toxicity were tested. SNP-SNP combinations (named SNP-allele sets) seen in ≥10% of the cohort were condensed into risk (RS) and protection (PS) scores, respectively indicating increased or decreased toxicity risk. Performance of RS and PS was evaluated by logistic regression. RS and PS were then combined into a single PRSi evaluated by area under the receiver operating characteristic curve (AUC). RESULTS: Among 1,387 analysed patients, toxicity rates were 11.7% (rectal bleeding), 4.0% (urinary frequency), 5.5% (haematuria), 7.8% (nocturia) and 17.1% (decreased urinary stream). RS and PS combined 8 to 15 different SNP-allele sets, depending on the toxicity endpoint. Distributions of PRSi differed significantly in patients with/without toxicity with AUCs ranging from 0.61 to 0.78. PRSi was better than the classical summed PRS, particularly for the urinary frequency, haematuria and decreased urinary stream endpoints. CONCLUSIONS: Our method incorporates SNP-SNP interactions when calculating PRS for radiotherapy toxicity. Our approach is better than classical summation in discriminating patients with toxicity and should enable incorporating genetic information to improve normal tissue complication probability models. ispartof: RADIOTHERAPY AND ONCOLOGY vol:159 pages:241-248 ispartof: location:Ireland status: published |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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Full Text from ScienceDirect 