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@ARTICLE{Kerns:178629,
      author       = {S. L. Kerns and A. Amidon Morlang and S. M. Lee and D. R.
                      Peterson and B. Marples and H. Zhang and K. Bylund and D.
                      Rosenzweig and W. Hall and K. De Ruyck and B. S. Rosenstein
                      and R. G. Stock and A. Gómez-Caamaño and A. Vega and P.
                      Sosa-Fajardo and B. Taboada-Valladares and M. E.
                      Aguado-Barrera and C. Parker and L. Veldeman and V. Fonteyne
                      and R. Bultijnck and C. J. Talbot and R. Paul Symonds and K.
                      Johnson and T. Rattay and A. Webb and M. Lambrecht and D. de
                      Ruysscher and B. Vanneste and A. Choudhury and R. M. Elliott
                      and E. Sperk and C. Herskind and M. R. Veldwijk and T.
                      Rancati and B. Avuzzi and R. Valdagni and D. Azria and M.-P.
                      Farcy Jacquet and J. Chang-Claude$^*$ and P. Seibold$^*$ and
                      C. West and M. Janelsins and Y. Chen and E. Messing and G.
                      Morrow and D. Azria and E. Briers and J. Chang-Claude$^*$
                      and A. Choudhury and A. Dunning and R. M. Elliott and S.
                      Gutiérrez-Enríquez and T. Rancati and T. Rattay and B. S.
                      Rosenstein and D. De Ruysscher and P. Seibold$^*$ and E.
                      Sperk and R. Paul Symonds and H. Stobart and C. J. Talbot
                      and A. Vega and L. Veldeman and T. Ward and A. Webb and C.
                      M. West},
      collaboration = {R. Consortium},
      title        = {{U}se of {A}ngiotensin {C}onverting {E}nzyme {I}nhibitors
                      is {A}ssociated with {R}educed {R}isk of {L}ate {B}ladder
                      {T}oxicity {F}ollowing {R}adiotherapy for {P}rostate
                      {C}ancer.},
      journal      = {Radiotherapy and oncology},
      volume       = {168},
      issn         = {0167-8140},
      address      = {Amsterdam [u.a.]},
      publisher    = {Elsevier Science},
      reportid     = {DKFZ-2022-00170},
      pages        = {75-82},
      year         = {2022},
      note         = {Volume 168, March 2022, Pages 75-82},
      abstract     = {Genome-wide association studies (GWAS) of late hematuria
                      following prostate cancer radiotherapy identified single
                      nucleotide polymorphisms (SNPs) near AGT, encoding
                      angiotensinogen. We tested the hypothesis that patients
                      taking angiotensin converting enzyme inhibitors (ACEi) have
                      a reduced risk of late hematuria. We additionally tested
                      genetically-defined hypertension.Prostate cancer patients
                      undergoing potentially-curative radiotherapy were enrolled
                      onto two multi-center observational studies, URWCI (N=256)
                      and REQUITE (N=1,437). Patients were assessed
                      pre-radiotherapy and followed prospectively for development
                      of toxicity for up to four years. The cumulative probability
                      of hematuria was estimated by the Kaplan-Meier method.
                      Multivariable grouped relative risk models assessed the
                      effect of ACEi on time to hematuria adjusting for clinical
                      factors and stratified by enrollment site. A polygenic risk
                      score (PRS) for blood pressure was tested for association
                      with hematuria in REQUITE and our Radiogenomics Consortium
                      GWAS.Patients taking ACEi during radiotherapy had a reduced
                      risk of hematuria (HR 0.51, $95\%CI$ 0.28 to 0.94, p=0.030)
                      after adjusting for prior transurethral prostate and/or
                      bladder resection, heart disease, pelvic node radiotherapy,
                      and bladder volume receiving 70 Gy, which are associated
                      with hematuria. A blood pressure PRS was associated with
                      hypertension (odds ratio per standard deviation 1.38,
                      $95\%CI$ 1.31 to 1.46, n=5,288, p<0.001) but not hematuria
                      (HR per standard deviation 0.96, $95\%CI$ 0.87 to 1.06,
                      n=5,126, p=0.41).Our study is the first to show a
                      radioprotective effect of ACEi on bladder in an
                      international, multi-site study of patients receiving pelvic
                      radiotherapy. Mechanistic studies are needed to understand
                      how targeting the angiotensin pathway protects the bladder.},
      cin          = {C020},
      ddc          = {610},
      cid          = {I:(DE-He78)C020-20160331},
      pnm          = {313 - Krebsrisikofaktoren und Prävention (POF4-313)},
      pid          = {G:(DE-HGF)POF4-313},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:35077710},
      doi          = {10.1016/j.radonc.2022.01.014},
      url          = {https://inrepo02.dkfz.de/record/178629},
}