{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T15:58:02Z","timestamp":1791475082267,"version":"4.3.4"},"reference-count":39,"publisher":"The Endocrine Society","issue":"12","license":[{"start":{"date-parts":[[2025,4,15]],"date-time":"2025-04-15T00:00:00Z","timestamp":1744675200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["1R21CA282380"],"award-info":[{"award-number":["1R21CA282380"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011866","name":"Colorado Clinical and Translational Sciences Institute","doi-asserted-by":"publisher","award":["CO-J-24-170"],"award-info":[{"award-number":["CO-J-24-170"]}],"id":[{"id":"10.13039\/100011866","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,11,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Context<\/jats:title>\n                    <jats:p>Understanding the population prevalence of thyroid cancer\u2013associated syndromes is important to guide germline genetic testing and clinical management.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To estimate the prevalence of the major thyroid cancer\u2013associated syndromes in the United States using data from the All of Us Research Program (All of Us) and the UK Biobank.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this cross-sectional study, we identified pathogenic and likely pathogenic (P\/LP) variants from the ClinVar database in 245 394 All of Us and 469 558 UK Biobank participants. We calculated the prevalence of thyroid cancer\u2013associated syndromes defined by the presence of P\/LP variants.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Using logistic regression, we found that 3 hereditary syndromes, multiple endocrine neoplasia type 2 (MEN2, RET gene, P = 3.23e-20), PTEN hamartoma tumor syndrome (PHTS, PTEN gene, P = 2.59e-15), and familial adenomatous polyposis type 1 (FAP, APC gene, P = 2.73e-10) were significantly associated with thyroid cancer. The prevalence of thyroid cancer\u2013associated syndromes in the All of Us was 1:2172, 1:8764, and 1:8461, and in the UK Biobank, it was 1:2348, 1:13 043, and 1:8238 for MEN2, PHTS, and FAP, respectively. Three pathogenic RET variants that cause 2 amino acid substitutions, V804M and V804L, constitute 65% of all MEN2 variants in the All of Us, and none of these carriers were diagnosed with thyroid cancer.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The prevalence of MEN2 and PHTS is \u223c10 to 20 times higher than is currently estimated for the general population. Most affected individuals are not diagnosed with thyroid cancer. Our findings may change the clinical approach to patients with moderate-risk RET mutations.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/clinem\/dgaf236","type":"journal-article","created":{"date-parts":[[2025,4,12]],"date-time":"2025-04-12T16:39:34Z","timestamp":1744475974000},"page":"e4049-e4054","source":"Crossref","is-referenced-by-count":17,"title":["Population Prevalence of the Major Thyroid Cancer\u2013Associated Syndromes"],"prefix":"10.1210","volume":"110","author":[{"given":"Samantha Lee","family":"White","sequence":"first","affiliation":[{"name":"Division of Endocrinology, Diabetes and Metabolism, University of Colorado Anschutz Medical Campus , Aurora, CO 80045 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taylor","family":"Jamil","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, University of Colorado Anschutz Medical Campus , Aurora, CO 80045 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