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000180699 1001_ $$aBarnett, Gillian C$$b0
000180699 245__ $$aNo association between polygenic risk scores for cancer and development of radiotherapy toxicity.
000180699 260__ $$aAmsterdam [u.a.]$$bElsevier Science$$c2022
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000180699 500__ $$a 2022 Nov 1;114(3):494-501
000180699 520__ $$aTo test whether updated polygenic risk scores (PRS) for susceptibility to cancer affect risk of radiotherapy toxicity.Analyses included 9,717 patients with breast (n=3,078), prostate (n=5,748) or lung (n=891) cancer from XXXX and XXXX Consortia cohorts. Patients underwent potentially curative radiotherapy and were assessed prospectively for toxicity. Germline genotyping involved genome-wide single nucleotide polymorphism (SNP) arrays with non-typed SNPs imputed. PRS for each cancer were generated by summing literature-identified cancer susceptibility risk alleles: 352 breast, 136 prostate, 24 lung. Weighted PRS were generated using log odds ratios for cancer susceptibility. Standardized total average toxicity (STAT) scores at 2 and 5 years (breast, prostate) or 6 to 12 months (lung) quantified toxicity. Primary analysis tested late STAT, secondary analyses investigated acute STAT, and individual endpoints and SNPs using multivariable regression.Increasing PRS did not increase risk of late toxicity in patients with breast (OR 1.000, 95%CI 0.997-1.002), prostate (OR 0.99, 95%CI 0.98-1.00; weighted PRS OR 0.93, 95%CI 0.83-1.03) or lung (OR 0.93, 95%CI 0.87-1.00; weighted PRS OR 0.68, 95%CI 0.45-1.03) cancer. Similar results were seen for acute toxicity. Secondary analyses identified rs138944387 associated with breast pain (OR=3.05; 95%CI 1.86- 5.01; P=1.09 × 10-5) and rs17513613 with breast oedema (OR=0.94; 95%CI 0.92- 0.97; P=1.08 × 1 0-5).Patients with increased polygenic predisposition to breast, prostate or lung cancer can safely undergo radiotherapy with no anticipated excess toxicity risk. Some individual SNPs increase likelihood of a specific toxicity endpoint warranting validation in independent cohorts and functional studies to elucidate biologic mechanisms.
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000180699 7001_ $$aKerns, Sarah L$$b1
000180699 7001_ $$aDorling, Leila$$b2
000180699 7001_ $$aFachal, Laura$$b3
000180699 7001_ $$aAguado-Barrera, Miguel E$$b4
000180699 7001_ $$aMartínez-Calvo, Laura$$b5
000180699 7001_ $$aJandu, Harkeran K$$b6
000180699 7001_ $$aWelsh, Ceilidh$$b7
000180699 7001_ $$aTyrer, Jonathan$$b8
000180699 7001_ $$aColes, Charlotte E$$b9
000180699 7001_ $$aHaviland, Joanne S$$b10
000180699 7001_ $$aParker, Christopher$$b11
000180699 7001_ $$aGómez-Caamaño, Antonio$$b12
000180699 7001_ $$aCalvo-Crespo, Patricia$$b13
000180699 7001_ $$aSosa-Fajardo, Paloma$$b14
000180699 7001_ $$aBurnet, Neil G$$b15
000180699 7001_ $$aSummersgill, Holly$$b16
000180699 7001_ $$aWebb, Adam$$b17
000180699 7001_ $$aDe Ruysscher, Dirk$$b18
000180699 7001_ $$0P:(DE-He78)fd17a8dbf8d08ea5bb656dfef7398215$$aSeibold, Petra$$b19$$udkfz
000180699 7001_ $$0P:(DE-He78)c259d6cc99edf5c7bc7ce22c7f87c253$$aChang-Claude, Jenny$$b20$$udkfz
000180699 7001_ $$aTalbot, Christopher J$$b21
000180699 7001_ $$aRattay, Tim$$b22
000180699 7001_ $$aParliament, Matthew$$b23
000180699 7001_ $$aDe Ruyck, Kim$$b24
000180699 7001_ $$aRosenstein, Barry S$$b25
000180699 7001_ $$aPharoah, Paul D P$$b26
000180699 7001_ $$aDunning, Alison M$$b27
000180699 7001_ $$aVega, Ana$$b28
000180699 7001_ $$aWest, Catharine M L$$b29
000180699 773__ $$0PERI:(DE-600)1500486-7$$a10.1016/j.ijrobp.2022.06.098$$gp. S0360301622007076$$n3$$p494-501$$tInternational journal of radiation oncology, biology, physics$$v114$$x0360-3016$$y2022
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