{"doi":"10.1016/j.ijrobp.2022.06.098","title":"No Association Between Polygenic Risk Scores for Cancer and Development of Radiation Therapy Toxicity","abstract":"<h3>Purpose</h3> Our aim was to test whether updated polygenic risk scores (PRS) for susceptibility to cancer affect risk of radiation therapy toxicity. <h3>Methods and Materials</h3> Analyses included 9,717 patients with breast (n=3,078), prostate (n=5,748) or lung (n=891) cancer from Radiogenomics and REQUITE Consortia cohorts. Patients underwent potentially curative radiation therapy and were assessed prospectively for toxicity. Germline genotyping involved genome-wide single nucleotide polymorphism (SNP) arrays with nontyped SNPs imputed. PRS for each cancer were generated by summing literature-identified cancer susceptibility risk alleles: 352 breast, 136 prostate, and 24 lung. Weighted PRS were generated using log odds ratio (ORs) 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. <h3>Results</h3> Increasing PRS did not increase risk of late toxicity in patients with breast (OR, 1.000; 95% confidence interval [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; <i>P</i> = 1.09 × 10<sup>–5</sup>) and rs17513613 with breast edema (OR, 0.94; 95% CI, 0.92-0.97; <i>P</i> = 1.08 × 10<sup>–5</sup>). <h3>Conclusions</h3> Patients with increased polygenic predisposition to breast, prostate, or lung cancer can safely undergo radiation therapy with no anticipated excess toxicity risk. Some individual SNPs increase the likelihood of a specific toxicity endpoint, warranting validation in independent cohorts and functional studies to elucidate biologic mechanisms.","journal":"International Journal of Radiation Oncology*Biology*Physics","year":2022,"id":285169,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.6853,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":536709,"name":"Sarah L. 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Talbot","orcid":"0000-0001-7406-8962","position":21,"is_corresponding":false},{"id":963360,"name":"Tim Rattay","orcid":"0000-0002-2824-4854","position":22,"is_corresponding":false},{"id":748391,"name":"Matthew Parliament","orcid":"0000-0002-5091-9344","position":23,"is_corresponding":false},{"id":240097,"name":"Kim De Ruyck","orcid":"0000-0001-9921-644X","position":24,"is_corresponding":false},{"id":240092,"name":"Barry S. Rosenstein","orcid":"0000-0002-3149-3237","position":25,"is_corresponding":false},{"id":33596,"name":"Paul D.P. Pharoah","orcid":"0000-0001-8494-732X","position":26,"is_corresponding":false},{"id":16417,"name":"Alison M. Dunning","orcid":"0000-0001-6651-7166","position":27,"is_corresponding":false},{"id":240093,"name":"Ana Vega","orcid":"0000-0002-7416-5137","position":28,"is_corresponding":false},{"id":240084,"name":"Catharine West","orcid":"0000-0002-0839-3449","position":29,"is_corresponding":false},{"id":963349,"name":"Gillian C. 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