%0 Journal Article
%A Farazi, Manzur
%A Yang, Xin
%A Gehl, Carson J
%A Barnett, Gillian C
%A Burnet, Neil G
%A Chang-Claude, Jenny
%A Parker, Christopher C
%A Dunning, Alison M
%A Azria, David
%A Choudhury, Ananya
%A Rancati, Tiziana
%A De Ruysscher, Dirk
%A Seibold, Petra
%A Sperk, Elena
%A Talbot, Christopher J
%A Veldeman, Liv
%A Webb, Adam J
%A Elliott, Rebecca
%A Aguado-Barrera, Miguel E
%A Carballo, Ana M
%A Fuentes-Ríos, Olivia
%A Gómez-Caamaño, Antonio
%A Peleteiro, Paula
%A Vega, Ana
%A Ostrer, Harry
%A Rosenstein, Barry S
%A Saito, Shiro
%A Parliament, Matthew
%A Usmani, Nawaid
%A Marples, Brian
%A Chen, Yuhchyau
%A Morrow, Gary
%A Messing, Edward
%A Janelsins, Michelle C
%A Hall, William
%A West, Catharine M L
%A Auer, Paul L
%A Kerns, Sarah
%T A Polygenic Risk Score for Late Bladder Toxicity Following Radiotherapy for Non-Metastatic Prostate Cancer.
%J Cancer epidemiology, biomarkers & prevention
%V 34
%N 5
%@ 1055-9965
%C Philadelphia, Pa.
%I AACR
%M DKFZ-2025-00477
%P 795-804
%D 2025
%Z 2025 May 2;34(5):795-804
%X Late bladder toxicity is a concern for patients receiving prostate cancer radiotherapy and negatively impacts survivors. Few risk factors are known beyond the radiation dose and volume of bladder exposed. A polygenic risk score (PRS) could identify susceptible patients.A PRS was built using genome-wide association results from the Radiogenomics Consortium (N=3,988), then tested in the prospective REQUITE and URWCI studies (N=2,034). The primary outcome was time-to-patient-reported gross (≥ grade 2, G2) hematuria analyzed using Cox proportional hazards regression. Secondary outcomes were ≥G2 urinary retention and frequency. The PRS was externally validated for clinically-diagnosed irradiation cystitis in the UK Biobank (N=8,430). A gene-burden test evaluated rare coding variants.A 115-variant PRS was associated with significantly increased risk of ≥G2 hematuria (hazard ratio [HR] per standard deviation [SD]=1.22, p=0.009) as well as urinary retention (HR-per-SD=1.18, p=0.016) and frequency (HR-per-SD=1.14, p=0.036). When binarized, men in the upper decile (PRShigh) had >2-fold increased risk of hematuria after adjusting for clinical risk factors (HR=2.12, p=0.002; Harrel's c-index 0.71 [95
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:40029246
%R 10.1158/1055-9965.EPI-24-1228
%U https://inrepo02.dkfz.de/record/299519