Journal Article

DKFZ-2022-00170

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Use of Angiotensin Converting Enzyme Inhibitors is Associated with Reduced Risk of Late Bladder Toxicity Following Radiotherapy for Prostate Cancer.

Kerns, S. L. ; Amidon Morlang, A. ; Lee, S. M. ; Peterson, D. R. ; Marples, B. ; Zhang, H. ; Bylund, K. ; Rosenzweig, D. ; Hall, W. ; De Ruyck, K. ; Rosenstein, B. S. ; Stock, R. G. ; Gómez-Caamaño, A. ; Vega, A. ; Sosa-Fajardo, P. ; Taboada-Valladares, B. ; Aguado-Barrera, M. E. ; Parker, C. ; Veldeman, L. ; Fonteyne, V. ; Bultijnck, R. ; Talbot, C. J. ; Paul Symonds, R. ; Johnson, K. ; Rattay, T. ; Webb, A. ; Lambrecht, M. ; de Ruysscher, D. ; Vanneste, B. ; Choudhury, A. ; Elliott, R. M. ; Sperk, E. ; Herskind, C. ; Veldwijk, M. R. ; Rancati, T. ; Avuzzi, B. ; Valdagni, R. ; Azria, D. ; Farcy Jacquet, M.-P. ; Chang-Claude, J.DKFZ* ; Seibold, P.DKFZ* ; West, C. ; Janelsins, M. ; Chen, Y. ; Messing, E. ; Morrow, G. ; Consortium, R. (Collaboration Author) ; Azria, D. ; Briers, E. ; Chang-Claude, J.DKFZ* ; Choudhury, A. ; Dunning, A. ; Elliott, R. M. ; Gutiérrez-Enríquez, S. ; Rancati, T. ; Rattay, T. ; Rosenstein, B. S. ; De Ruysscher, D. ; Seibold, P.DKFZ* ; Sperk, E. ; Paul Symonds, R. ; Stobart, H. ; Talbot, C. J. ; Vega, A. ; Veldeman, L. ; Ward, T. ; Webb, A. ; West, C. M.

2022
Elsevier Science Amsterdam [u.a.]

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Please use a persistent id in citations: doi:10.1016/j.radonc.2022.01.014

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.

Note: Volume 168, March 2022, Pages 75-82

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Contributing Institute(s):

1. C020 Epidemiologie von Krebs (C020)

Research Program(s):

1. 313 - Krebsrisikofaktoren und Prävention (POF4-313) (POF4-313)

Appears in the scientific report 2022

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 5 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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