{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T13:50:37Z","timestamp":1781877037614,"version":"3.54.5"},"reference-count":39,"publisher":"BMJ","issue":"6","license":[{"start":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T00:00:00Z","timestamp":1781827200000},"content-version":"unspecified","delay-in-days":18,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Bristol Myers Squibb","award":["E1609"],"award-info":[{"award-number":["E1609"]}]},{"name":"NCI\/NIH ECOG-ACRIN Cancer Research Group","award":["U10CA180794, U10CA180820, UG1CA233180, UG1CA233184"],"award-info":[{"award-number":["U10CA180794, U10CA180820, UG1CA233180, UG1CA233184"]}]},{"DOI":"10.13039\/100006827","name":"Florida Department of Health","doi-asserted-by":"publisher","award":["23B09"],"award-info":[{"award-number":["23B09"]}],"id":[{"id":"10.13039\/100006827","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NCI\/NIH Cancer Center Support Grant (CCSG) to Moffitt Cancer Center","award":["CA076292"],"award-info":[{"award-number":["CA076292"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2026,6,1]]},"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Inherited genetic variation may impact patient response and risk of toxicity following immune checkpoint inhibitor (ICI) therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted an agnostic genome-wide analysis study for inherited genetic variants that may predict thyroiditis in patients with melanoma treated with ipilimumab and investigated Polygenic Risk Scores (PRSs) previously reported to be associated with thyroid disease. Germline DNA from 744 participants in a phase 3 adjuvant trial was analyzed following genome-wide genotyping.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      An agnostic genome-wide cohort-level analysis identified top associated single nucleotide polymorphisms (SNPs), and a custom 10-SNP PRS was significantly associated with thyroiditis risk and severity. Among the SNPs identified, five mapped to intronic, four intergenic and one exonic regions. The latter was the lead SNP and mapped to\n                      <jats:italic>CNOT6L<\/jats:italic>\n                      , located near\n                      <jats:italic>CXCL13<\/jats:italic>\n                      . Among the other variants, most were located within regions with potential relevance to immune regulation and autoimmunity. Separately, multiple thyroid disease-related PRSs derived from Polygenic Score Catalog weights were tested, and several were significantly associated with thyroiditis, but the custom PRS had stronger discrimination for thyroiditis risk (area under the curve 0.82).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings indicate that inherited genetic background contributes to thyroid immune toxicity risk following ICI and support PRS-based approaches for risk-adapted monitoring during immunotherapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jitc-2026-015413","type":"journal-article","created":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T12:50:35Z","timestamp":1781873435000},"page":"e015413","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Predicting immune-related thyroiditis using polygenic risk scores in patients with advanced melanoma"],"prefix":"10.1136","volume":"14","clinical-trial-number":[{"clinical-trial-number":"nct01274338","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3193-9702","authenticated-orcid":false,"given":"Ahmad A","family":"Tarhini","sequence":"first","affiliation":[{"name":"Department of Immunology, H Lee Moffitt Cancer Center and Research Center, Tampa, Florida, USA"},{"name":"Department of Cutaneous Oncology, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad Ali","family":"Khaksar","sequence":"additional","affiliation":[{"name":"Department of Cutaneous Oncology, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihua","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Bioinformatics, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra J","family":"Lee","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F","family":"Stephen Hodi","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingyi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Bioinformatics, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean J","family":"Yoder","sequence":"additional","affiliation":[{"name":"Molecular Genomics Core Facility, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Howard","family":"Streicher","sequence":"additional","affiliation":[{"name":"Cancer Therapy Evaluation Program, National Cancer Institute, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vernon K","family":"Sondak","sequence":"additional","affiliation":[{"name":"Department of Cutaneous Oncology, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3570-4476","authenticated-orcid":false,"given":"John M","family":"Kirkwood","sequence":"additional","affiliation":[{"name":"Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5775-408X","authenticated-orcid":false,"given":"Xuefeng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Bioinformatics, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5567-9618","authenticated-orcid":false,"given":"Peter A","family":"Kanetsky","sequence":"additional","affiliation":[{"name":"Department of Cancer Epidemiology, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2026,6,19]]},"reference":[{"key":"2026061905502668000_14.6.e015413.1","article-title":"Cancer statistics, 2026","volume":"76","author":"Siegel","year":"2026","journal-title":"CA Cancer J 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