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Verfasst von:Franco, Nicola Rares [VerfasserIn]   i
 Massi, Michela Carlotta [VerfasserIn]   i
 Ieva, Francesca [VerfasserIn]   i
 Manzoni, Andrea [VerfasserIn]   i
 Paganoni, Anna Maria [VerfasserIn]   i
 Zunino, Paolo [VerfasserIn]   i
 Veldeman, Liv [VerfasserIn]   i
 Ost, Piet [VerfasserIn]   i
 Fonteyne, Valérie [VerfasserIn]   i
 Talbot, Christopher J. [VerfasserIn]   i
 Rattay, Tim [VerfasserIn]   i
 Webb, Adam [VerfasserIn]   i
 Johnson, Kerstie [VerfasserIn]   i
 Lambrecht, Maarten [VerfasserIn]   i
 Haustermans, Karin [VerfasserIn]   i
 Meerleer, Gert De [VerfasserIn]   i
 Ruysscher, Dirk de [VerfasserIn]   i
 Vanneste, Ben [VerfasserIn]   i
 Limbergen, Evert van [VerfasserIn]   i
 Choudhury, Ananya [VerfasserIn]   i
 Elliott, Rebecca M. [VerfasserIn]   i
 Sperk, Elena [VerfasserIn]   i
 Veldwijk, Marlon Romano [VerfasserIn]   i
 Herskind, Carsten [VerfasserIn]   i
 Avuzzi, Barbara [VerfasserIn]   i
 Noris Chiorda, Barbara [VerfasserIn]   i
 Valdagni, Riccardo [VerfasserIn]   i
 Azria, David [VerfasserIn]   i
 Farcy-Jacquet, Marie-Pierre [VerfasserIn]   i
 Brengues, Muriel [VerfasserIn]   i
 Rosenstein, Barry S. [VerfasserIn]   i
 Stock, Richard G. [VerfasserIn]   i
 Vega, Ana [VerfasserIn]   i
 Aguado-Barrera, Miguel E. [VerfasserIn]   i
 Sosa-Fajardo, Paloma [VerfasserIn]   i
 Dunning, Alison M. [VerfasserIn]   i
 Fachal, Laura [VerfasserIn]   i
 Kerns, Sarah L. [VerfasserIn]   i
 Payne, Debbie [VerfasserIn]   i
 Chang-Claude, Jenny [VerfasserIn]   i
 Seibold, Petra [VerfasserIn]   i
 West, Catharine M. L. [VerfasserIn]   i
 Rancati, Tiziana [VerfasserIn]   i
Titel:Development of a method for generating SNP interaction-aware polygenic risk scores for radiotherapy toxicity
Verf.angabe:Nicola Rares Franco, Michela Carlotta Massi, Francesca Ieva, Andrea Manzoni, Anna Maria Paganoni, Paolo Zunino, Liv Veldeman, Piet Ost, Valérie Fonteyne, Christopher J. Talbot, Tim Rattay, Adam Webb, Kerstie Johnson, Maarten Lambrecht, Karin Haustermans, Gert De Meerleer, Dirk de Ruysscher, Ben Vanneste, Evert Van Limbergen, Ananya Choudhury, Rebecca M. Elliott, Elena Sperk, Marlon R. Veldwijk, Carsten Herskind, Barbara Avuzzi, Barbara Noris Chiorda, Riccardo Valdagni, David Azria, Marie-Pierre Farcy-Jacquet, Muriel Brengues, Barry S. Rosenstein, Richard G. Stock, Ana Vega, Miguel E. Aguado-Barrera, Paloma Sosa-Fajardo, Alison M. Dunning, Laura Fachal, Sarah L. Kerns, Debbie Payne, Jenny Chang-Claude, Petra Seibold, Catharine M. L. West, Tiziana Rancati, REQUITE Consortium
E-Jahr:2021
Jahr:8 April 2021
Umfang:8 S.
Teil:volume:159
 year:2021
 pages:241-248
 extent:8
Fussnoten:Gesehen am 06.08.2021
Titel Quelle:Enthalten in: Radiotherapy and oncology
Ort Quelle:Amsterdam [u.a.] : Elsevier Science, 1983
Jahr Quelle:2021
Band/Heft Quelle:159(2021), Seite 241-248
ISSN Quelle:1879-0887
Abstract: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 2years. 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.
DOI:doi:10.1016/j.radonc.2021.03.024
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

Volltext ; Verlag: https://doi.org/10.1016/j.radonc.2021.03.024
 Volltext: https://www.sciencedirect.com/science/article/pii/S0167814021061612
 DOI: https://doi.org/10.1016/j.radonc.2021.03.024
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:Radiotherapy
 Epistasis
 Genetic risk factors
 Late toxicity
 Prostate cancer
 SNPs
K10plus-PPN:176585640X
Verknüpfungen:→ Zeitschrift

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