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@ARTICLE{Farazi:299519,
      author       = {M. Farazi and X. Yang and C. J. Gehl and G. C. Barnett and
                      N. G. Burnet and J. Chang-Claude$^*$ and C. C. Parker and A.
                      M. Dunning and D. Azria and A. Choudhury and T. Rancati and
                      D. De Ruysscher and P. Seibold$^*$ and E. Sperk and C. J.
                      Talbot and L. Veldeman and A. J. Webb and R. Elliott and M.
                      E. Aguado-Barrera and A. M. Carballo and O. Fuentes-Ríos
                      and A. Gómez-Caamaño and P. Peleteiro and A. Vega and H.
                      Ostrer and B. S. Rosenstein and S. Saito and M. Parliament
                      and N. Usmani and B. Marples and Y. Chen and G. Morrow and
                      E. Messing and M. C. Janelsins and W. Hall and C. M. L. West
                      and P. L. Auer and S. Kerns},
      title        = {{A} {P}olygenic {R}isk {S}core for {L}ate {B}ladder
                      {T}oxicity {F}ollowing {R}adiotherapy for {N}on-{M}etastatic
                      {P}rostate {C}ancer.},
      journal      = {Cancer epidemiology, biomarkers $\&$ prevention},
      volume       = {34},
      number       = {5},
      issn         = {1055-9965},
      address      = {Philadelphia, Pa.},
      publisher    = {AACR},
      reportid     = {DKFZ-2025-00477},
      pages        = {795-804},
      year         = {2025},
      note         = {2025 May 2;34(5):795-804},
      abstract     = {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 $[95\%CI=0.65$ to 0.76]). A similar
                      effect size was seen in the UK Biobank for
                      clinically-diagnosed irradiation cystitis (OR=2.15,
                      p=0.026). The burden test identified BOD1L1 as a putative
                      novel radiosensitivity gene.This PRS identifies susceptible
                      patients and could guide selection of those needing
                      re-optimized treatment plans that spare the bladder beyond
                      currently recommended constraints.PRS-guided treatment
                      planning in radiation oncology could lower the incidence of
                      clinically relevant bladder toxicity and reduce the impact
                      of this outcome on prostate cancer survivors.},
      cin          = {C020 / C130},
      ddc          = {610},
      cid          = {I:(DE-He78)C020-20160331 / I:(DE-He78)C130-20160331},
      pnm          = {313 - Krebsrisikofaktoren und Prävention (POF4-313)},
      pid          = {G:(DE-HGF)POF4-313},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40029246},
      doi          = {10.1158/1055-9965.EPI-24-1228},
      url          = {https://inrepo02.dkfz.de/record/299519},
}