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000178629 0247_ $$2ISSN$$a1879-0887
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000178629 037__ $$aDKFZ-2022-00170
000178629 041__ $$aEnglish
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000178629 1001_ $$aKerns, Sarah L$$b0
000178629 245__ $$aUse of Angiotensin Converting Enzyme Inhibitors is Associated with Reduced Risk of Late Bladder Toxicity Following Radiotherapy for Prostate Cancer.
000178629 260__ $$aAmsterdam [u.a.]$$bElsevier Science$$c2022
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000178629 500__ $$aVolume 168, March 2022, Pages 75-82
000178629 520__ $$aGenome-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.
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000178629 7001_ $$aAmidon Morlang, Ashley$$b1
000178629 7001_ $$aLee, Sharon M$$b2
000178629 7001_ $$aPeterson, Derick R$$b3
000178629 7001_ $$aMarples, Brian$$b4
000178629 7001_ $$aZhang, Hong$$b5
000178629 7001_ $$aBylund, Kevin$$b6
000178629 7001_ $$aRosenzweig, Doug$$b7
000178629 7001_ $$aHall, William$$b8
000178629 7001_ $$aDe Ruyck, Kim$$b9
000178629 7001_ $$aRosenstein, Barry S$$b10
000178629 7001_ $$aStock, Richard G$$b11
000178629 7001_ $$aGómez-Caamaño, Antonio$$b12
000178629 7001_ $$aVega, Ana$$b13
000178629 7001_ $$aSosa-Fajardo, Paloma$$b14
000178629 7001_ $$aTaboada-Valladares, Begoña$$b15
000178629 7001_ $$aAguado-Barrera, Miguel E$$b16
000178629 7001_ $$aParker, Chris$$b17
000178629 7001_ $$aVeldeman, Liv$$b18
000178629 7001_ $$aFonteyne, Valérie$$b19
000178629 7001_ $$aBultijnck, Renée$$b20
000178629 7001_ $$aTalbot, Christopher J$$b21
000178629 7001_ $$aPaul Symonds, R.$$b22
000178629 7001_ $$aJohnson, Kerstie$$b23
000178629 7001_ $$aRattay, Tim$$b24
000178629 7001_ $$aWebb, Adam$$b25
000178629 7001_ $$aLambrecht, Maarten$$b26
000178629 7001_ $$ade Ruysscher, Dirk$$b27
000178629 7001_ $$aVanneste, Ben$$b28
000178629 7001_ $$aChoudhury, Ananya$$b29
000178629 7001_ $$aElliott, Rebecca M$$b30
000178629 7001_ $$aSperk, Elena$$b31
000178629 7001_ $$aHerskind, Carsten$$b32
000178629 7001_ $$aVeldwijk, Marlon R$$b33
000178629 7001_ $$aRancati, Tiziana$$b34
000178629 7001_ $$aAvuzzi, Barbara$$b35
000178629 7001_ $$aValdagni, Riccardo$$b36
000178629 7001_ $$aAzria, David$$b37
000178629 7001_ $$aFarcy Jacquet, Marie-Pierre$$b38
000178629 7001_ $$0P:(DE-He78)c259d6cc99edf5c7bc7ce22c7f87c253$$aChang-Claude, Jenny$$b39$$udkfz
000178629 7001_ $$0P:(DE-He78)fd17a8dbf8d08ea5bb656dfef7398215$$aSeibold, Petra$$b40$$udkfz
000178629 7001_ $$aWest, Catharine$$b41
000178629 7001_ $$aJanelsins, Michelle$$b42
000178629 7001_ $$aChen, Yuhchyau$$b43
000178629 7001_ $$aMessing, Edward$$b44
000178629 7001_ $$aMorrow, Gary$$b45
000178629 7001_ $$aConsortium, REQUITE$$b46$$eCollaboration Author
000178629 7001_ $$aAzria, David$$b47
000178629 7001_ $$aBriers, Erik$$b48
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000178629 7001_ $$aChoudhury, Ananya$$b50
000178629 7001_ $$aDunning, Alison$$b51
000178629 7001_ $$aElliott, Rebecca M$$b52
000178629 7001_ $$aGutiérrez-Enríquez, Sara$$b53
000178629 7001_ $$aRancati, Tiziana$$b54
000178629 7001_ $$aRattay, Tim$$b55
000178629 7001_ $$aRosenstein, Barry S$$b56
000178629 7001_ $$aDe Ruysscher, Dirk$$b57
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000178629 7001_ $$aPaul Symonds, R.$$b60
000178629 7001_ $$aStobart, Hilary$$b61
000178629 7001_ $$aTalbot, Christopher J$$b62
000178629 7001_ $$aVega, Ana$$b63
000178629 7001_ $$aVeldeman, Liv$$b64
000178629 7001_ $$aWard, Tim$$b65
000178629 7001_ $$aWebb, Adam$$b66
000178629 7001_ $$aWest, Catharine M$$b67
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