TY  - JOUR
AU  - Farazi, Manzur
AU  - Yang, Xin
AU  - Gehl, Carson J
AU  - Barnett, Gillian C
AU  - Burnet, Neil G
AU  - Chang-Claude, Jenny
AU  - Parker, Christopher C
AU  - Dunning, Alison M
AU  - Azria, David
AU  - Choudhury, Ananya
AU  - Rancati, Tiziana
AU  - De Ruysscher, Dirk
AU  - Seibold, Petra
AU  - Sperk, Elena
AU  - Talbot, Christopher J
AU  - Veldeman, Liv
AU  - Webb, Adam J
AU  - Elliott, Rebecca
AU  - Aguado-Barrera, Miguel E
AU  - Carballo, Ana M
AU  - Fuentes-Ríos, Olivia
AU  - Gómez-Caamaño, Antonio
AU  - Peleteiro, Paula
AU  - Vega, Ana
AU  - Ostrer, Harry
AU  - Rosenstein, Barry S
AU  - Saito, Shiro
AU  - Parliament, Matthew
AU  - Usmani, Nawaid
AU  - Marples, Brian
AU  - Chen, Yuhchyau
AU  - Morrow, Gary
AU  - Messing, Edward
AU  - Janelsins, Michelle C
AU  - Hall, William
AU  - West, Catharine M L
AU  - Auer, Paul L
AU  - Kerns, Sarah
TI  - A Polygenic Risk Score for Late Bladder Toxicity Following Radiotherapy for Non-Metastatic Prostate Cancer.
JO  - Cancer epidemiology, biomarkers & prevention
VL  - 34
IS  - 5
SN  - 1055-9965
CY  - Philadelphia, Pa.
PB  - AACR
M1  - DKFZ-2025-00477
SP  - 795-804
PY  - 2025
N1  - 2025 May 2;34(5):795-804
AB  - 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
LB  - PUB:(DE-HGF)16
C6  - pmid:40029246
DO  - DOI:10.1158/1055-9965.EPI-24-1228
UR  - https://inrepo02.dkfz.de/record/299519
ER  -