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000168332 1001_ $$aRares Franco, Nicola$$b0
000168332 245__ $$aDevelopment of a method for generating SNP interaction-aware polygenic risk scores for radiotherapy toxicity.
000168332 260__ $$aAmsterdam [u.a.]$$bElsevier Science$$c2021
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000168332 500__ $$a2021 Apr 8;159:241-248
000168332 520__ $$aTo identify the effect of single nucleotide polymorphism (SNP) interactions on the risk of toxicity following radiotherapy (RT) for prostate cancer (PCa) and propose a new method for polygenic risk score incorporating SNP-SNP interactions (PRSi).Analysis included the REQUITE PCa cohort that received external beam RT and was followed for 2 years. Late toxicity endpoints were: rectal bleeding, urinary frequency, haematuria, nocturia, decreased urinary stream. Among 43 literature-identified SNPs, the 30% most strongly associated with each toxicity were tested. SNP-SNP combinations (named SNP-allele sets) seen in ≥10% of the cohort were condensed into risk (RS) and protection (PS) scores, respectively indicating increased or decreased toxicity risk. Performance of RS and PS was evaluated by logistic regression. RS and PS were then combined into a single PRSi evaluated by area under the receiver operating characteristic curve (AUC).Among 1,387 analysed patients, toxicity rates were 11.7% (rectal bleeding), 4.0% (urinary frequency), 5.5% (haematuria), 7.8% (nocturia) and 17.1% (decreased urinary stream). RS and PS combined 8 to 15 different SNP-allele sets, depending on the toxicity endpoint. Distributions of PRSi differed significantly in patients with/without toxicity with AUCs ranging from 0.61 to 0.78. PRSi was better than the classical summed PRS, particularly for the urinary frequency, haematuria and decreased urinary stream endpoints.Our method incorporates SNP-SNP interactions when calculating PRS for radiotherapy toxicity. Our approach is better than classical summation in discriminating patients with toxicity and should enable incorporating genetic information to improve normal tissue complication probability models.
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000168332 650_7 $$2Other$$aSNPs
000168332 650_7 $$2Other$$aepistasis
000168332 650_7 $$2Other$$agenetic risk factors
000168332 650_7 $$2Other$$alate toxicity
000168332 650_7 $$2Other$$aprostate cancer
000168332 650_7 $$2Other$$aradiotherapy
000168332 7001_ $$aCarlotta Massi, Michela$$b1
000168332 7001_ $$aIeva, Francesca$$b2
000168332 7001_ $$aManzoni, Andrea$$b3
000168332 7001_ $$aMaria Paganoni, Anna$$b4
000168332 7001_ $$aZunino, Paolo$$b5
000168332 7001_ $$aVeldeman, Liv$$b6
000168332 7001_ $$aOst, Piet$$b7
000168332 7001_ $$aFonteyne, Valérie$$b8
000168332 7001_ $$aTalbot, Christopher J$$b9
000168332 7001_ $$aRattay, Tim$$b10
000168332 7001_ $$aWebb, Adam$$b11
000168332 7001_ $$aJohnson, Kerstie$$b12
000168332 7001_ $$aLambrecht, Maarten$$b13
000168332 7001_ $$aHaustermans, Karin$$b14
000168332 7001_ $$aDe Meerleer, Gert$$b15
000168332 7001_ $$ade Ruysscher, Dirk$$b16
000168332 7001_ $$aVanneste, Ben$$b17
000168332 7001_ $$aVan Limbergen, Evert$$b18
000168332 7001_ $$aChoudhury, Ananya$$b19
000168332 7001_ $$aElliott, Rebecca M$$b20
000168332 7001_ $$aSperk, Elena$$b21
000168332 7001_ $$aVeldwijk, Marlon$$b22
000168332 7001_ $$aHerskind, Carsten$$b23
000168332 7001_ $$aAvuzzi, Barbara$$b24
000168332 7001_ $$aNoris Chiorda, Barbara$$b25
000168332 7001_ $$aValdagni, Riccardo$$b26
000168332 7001_ $$aAzria, David$$b27
000168332 7001_ $$aFarcy-Jacquet, Marie-Pierre$$b28
000168332 7001_ $$aBrengues, Muriel$$b29
000168332 7001_ $$aRosenstein, Barry S$$b30
000168332 7001_ $$aStock, Richard G$$b31
000168332 7001_ $$aVega, Ana$$b32
000168332 7001_ $$aElías Aguado-Barrera, Miguel$$b33
000168332 7001_ $$aSosa-Fajardo, Paloma$$b34
000168332 7001_ $$aDunning, Alison M$$b35
000168332 7001_ $$aFachal, Laura$$b36
000168332 7001_ $$aKerns, Sarah L$$b37
000168332 7001_ $$aPayne, Debbie$$b38
000168332 7001_ $$0P:(DE-He78)c259d6cc99edf5c7bc7ce22c7f87c253$$aChang-Claude, Jenny$$b39$$udkfz
000168332 7001_ $$0P:(DE-He78)fd17a8dbf8d08ea5bb656dfef7398215$$aSeibold, Petra$$b40$$udkfz
000168332 7001_ $$aMl West, Catharine$$b41
000168332 7001_ $$aRancati, Tiziana$$b42
000168332 7001_ $$aConsortium, REQUITE$$b43$$eCollaboration Author
000168332 7001_ $$aLievens, Yolande$$b44
000168332 7001_ $$avan Eijkeren, Marc$$b45
000168332 7001_ $$aMonten, Christel$$b46
000168332 7001_ $$aDe Neve, Wilfried$$b47
000168332 7001_ $$aPeeters, Stephanie$$b48
000168332 7001_ $$aWeltens, Caroline$$b49
000168332 7001_ $$aDefraene, Gilles$$b50
000168332 7001_ $$avan Limberghen, Erik$$b51
000168332 7001_ $$aBriers, Erik$$b52
000168332 7001_ $$aBourgier, Celine$$b53
000168332 7001_ $$aDraghici, Roxana$$b54
000168332 7001_ $$aBons, Francoise$$b55
000168332 7001_ $$aBlaschke, Thomas$$b56
000168332 7001_ $$aWeiß, Christian$$b57
000168332 7001_ $$aHelmbold, Irmgard$$b58
000168332 7001_ $$aWeißenberger, Christian$$b59
000168332 7001_ $$aStegmaier, Petra$$b60
000168332 7001_ $$aClaßen, Johannes$$b61
000168332 7001_ $$aGiesche, Ulrich$$b62
000168332 7001_ $$aSautter-Bihl, Marie-Luise$$b63
000168332 7001_ $$aNeu, Burkhard$$b64
000168332 7001_ $$aSchnabel, Thomas$$b65
000168332 7001_ $$aEhmann, Michael$$b66
000168332 7001_ $$aGauter-Fleckenstein, Benjamin$$b67
000168332 7001_ $$aSchäfer, Jörg$$b68
000168332 7001_ $$aGiandini, Tommaso$$b69
000168332 7001_ $$aFranceschini, Marzia$$b70
000168332 7001_ $$aSangalli, Claudia$$b71
000168332 7001_ $$aMorlino, Sara$$b72
000168332 7001_ $$aLozza, Laura$$b73
000168332 7001_ $$aDe Santis, Maria C$$b74
000168332 7001_ $$aPietro, Gabriele$$b75
000168332 7001_ $$aDelmastro, Elena$$b76
000168332 7001_ $$aGaribaldi, Elisabetta$$b77
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000168332 7001_ $$aMolla, Meritxel$$b80
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000168332 7001_ $$aLobato-Busto, Ramon$$b83
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000168332 7001_ $$aCalvo-Crespo, Patricia$$b87
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000168332 7001_ $$aLambert, Kelly V$$b108
000168332 7001_ $$aPilgrim, Simon$$b109
000168332 7001_ $$aShokuhi, Sheila$$b110
000168332 7001_ $$aValassiadou, Kalliope$$b111
000168332 7001_ $$aBioangiu, Ion$$b112
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000168332 7001_ $$aWard, Tim$$b119
000168332 7001_ $$aHigginson, Daniel S$$b120
000168332 7001_ $$aGreen, Sheryl$$b121
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