{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T14:48:22Z","timestamp":1787496502324,"version":"build-2736575974"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T00:00:00Z","timestamp":1736121600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union\u2018s Seventh Framework","award":["601826"],"award-info":[{"award-number":["601826"]}]},{"DOI":"10.13039\/100006662","name":"NIHR","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006662","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014653","name":"Manchester Biomedical Research Centre","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014653","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Cancer Research Manchester Centre","award":["C147\/A25254"],"award-info":[{"award-number":["C147\/A25254"]}]},{"name":"Cancer Research UK RadNet Manchester","award":["C1994\/A28701"],"award-info":[{"award-number":["C1994\/A28701"]}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DP50D031876"],"award-info":[{"award-number":["DP50D031876"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006662","name":"NIHR","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006662","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020013","name":"Leicester Biomedical Research Centre","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100020013","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Sara Guti\u00e9rrez-Enr\u00edquez","award":["ERAPerMed JTC2018"],"award-info":[{"award-number":["ERAPerMed JTC2018"]}]},{"name":"Sara Guti\u00e9rrez-Enr\u00edquez","award":["SLT011\/18\/00005"],"award-info":[{"award-number":["SLT011\/18\/00005"]}]},{"DOI":"10.13039\/501100002809","name":"Government of Catalonia","doi-asserted-by":"publisher","award":["2021SGR01112"],"award-info":[{"award-number":["2021SGR01112"]}],"id":[{"id":"10.13039\/501100002809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Vall d\u2019Hebron Institute of Oncology"},{"name":"Generalitat de Catalunya for institutional"},{"DOI":"10.13039\/501100011033","name":"Agencia Estatal de Investigaci\u00f3n","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100011033","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Center of Excellence Severo Ochoa","award":["CEX2020-001024-S\/AEI\/10.13039\/501100011033"],"award-info":[{"award-number":["CEX2020-001024-S\/AEI\/10.13039\/501100011033"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Overlapping genes are involved with rheumatoid arthritis (RA) and DNA repair pathways. Therefore, we hypothesized that patients with a high polygenic risk score for RA will have an increased risk of radiotherapy toxicity given the involvement of DNA repair.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Primary analysis was performed on 1494 prostate cancer, 483 lung cancer, and 1820 breast cancer patients assessed for development of radiotherapy toxicity in the REQUITE (validating pREdictive models and biomarkers of radiotherapy toxicity to reduce side effects and improve QUalITy of lifE in cancer survivors) study. Validation cohorts were available from the Radiogenomics Consortium. All patients had undergone curative-intent radiotherapy and were assessed prospectively for toxicity. Germline genomic data was available for all patients, allowing a polygenic risk score to be calculated using 101 RA risk variants. Polygenic risk score was analyzed as a continuous variable and with a more than 90th percentile cutoff. Associations with acute and late standardized total average toxicity (STAT) scores and individual toxicity endpoints were analyzed in multivariable models with preselected adjustment variables.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Increasing polygenic risk score for RA did not increase the risk of STAT-acute or\u00a0STAT-late in any cohort. There was an increased risk of late esophagitis in the lung cancer cohort (coefficient = 0.018, P\u2009=\u2009.01), however this was not validated (P\u2009=\u2009.79). No individual acute or late toxicity endpoints were statistically significantly associated with polygenic risk score for the prostate or breast cohorts. No statistically significant results were found in the validation cohorts in multivariable models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Patients with a high genetic risk for RA do not show increased levels of toxicity after radiotherapy suggesting treatment planning does not need to be modified for such patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jnci\/djae349","type":"journal-article","created":{"date-parts":[[2025,1,5]],"date-time":"2025-01-05T15:12:17Z","timestamp":1736089937000},"page":"1018-1026","source":"Crossref","is-referenced-by-count":2,"title":["Association of radiation-induced normal tissue toxicity with a high genetic risk for rheumatoid arthritis"],"prefix":"10.1093","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7344-2868","authenticated-orcid":false,"given":"Alan","family":"McWilliam","sequence":"first","affiliation":[{"name":"Division of Cancer Sciences, University of Manchester , Manchester,","place":["United Kingdom"]},{"name":"The Christie NHS Foundation Trust , Manchester,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6675-7482","authenticated-orcid":false,"given":"Deborah","family":"Marshall","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai , New York, NY,","place":["United States"]},{"name":"Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai , New York, NY,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6503-0011","authenticated-orcid":false,"given":"Sarah L","family":"Kerns","sequence":"additional","affiliation":[{"name":"Medical College of Wisconsin , Milwaukee, WI,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1762-5942","authenticated-orcid":false,"given":"Gillian C","family":"Barnett","sequence":"additional","affiliation":[{"name":"Oncology Centre, Cambridge University Hospitals NHS Foundation Trust , Cambridge,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7416-5137","authenticated-orcid":false,"given":"Ana","family":"Vega","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Sanitaria de Santiago de Compostela (IDIS) , Santiago de Compostela,","place":["Spain"]},{"name":"Fundaci\u00f3n P\u00fablica 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association between rheumatoid arthritis and risk of radiotherapy toxicity: a systematic review","volume":"3","author":"Liebenberg","year":"2024","journal-title":"BMJ Oncol"},{"key":"2025050719574268700_djae349-B2","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1038\/nature12873","article-title":"Genetics of rheumatoid arthritis contributes to biology and drug discovery","volume":"506","author":"Okada","year":"2014","journal-title":"Nature"},{"key":"2025050719574268700_djae349-B3","doi-asserted-by":"crossref","first-page":"3058","DOI":"10.1002\/art.38183","article-title":"Identification of BACH2 and RAD51B as rheumatoid arthritis susceptibility loci in a meta-analysis of genome-wide data","volume":"65","author":"McAllister","year":"2013","journal-title":"Arthritis Rheumatol"},{"key":"2025050719574268700_djae349-B4","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1002\/art.38353","article-title":"Novel risk loci for rheumatoid arthritis in Han Chinese and 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