{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T00:06:20Z","timestamp":1784073980927,"version":"3.55.0"},"reference-count":39,"publisher":"The Endocrine Society","issue":"8","license":[{"start":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T00:00:00Z","timestamp":1771977600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100021671","name":"US National Cancer Institute","doi-asserted-by":"publisher","award":["U01CA195547"],"award-info":[{"award-number":["U01CA195547"]}],"id":[{"id":"10.13039\/501100021671","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021671","name":"US National Cancer Institute","doi-asserted-by":"publisher","award":["R01 CA216354"],"award-info":[{"award-number":["R01 CA216354"]}],"id":[{"id":"10.13039\/501100021671","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012524","name":"American Lebanese Syrian Associated Charities","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012524","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Context<\/jats:title>\n                    <jats:p>Radiation to the hypothalamic-pituitary (HP) region (HP-RT) is a strong risk factor for HP deficiency among childhood cancer survivors (survivors). However, there is inter-individual variability in developing HP deficiency after similar HP-RT dose exposures.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To assess the genetic contribution to developing deficiencies of GH (GHD), LH\/FSH (LH\/FSHD), thyroid-stimulating hormone deficiency (thyroid-stimulating hormone deficiency [TSHD]), and ACTH (adrenocorticotropic hormone deficiency [ACTHD]) among survivors exposed to HP-RT.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Eligible participants included 5-year survivors exposed to HP-RT (n = 809; median follow-up 31.9 years) from the St. Jude Lifetime Cohort. We assessed the association between rare variants from whole-exome sequencing data (minor allele frequency [MAF] &amp;lt; 0.01, predicted to be pathogenic by functional prediction tools) and HP deficiency rate (total counts\/person-year) among 801 survivors by the exact Poisson test. Genome-wide association analysis (GWAS) was conducted among 606 survivors of European ancestry with available whole-genome sequence data, targeting variants with MAF \u2265 0.01. The replication population was 1328 survivors from the Childhood Cancer Survivor Study (CCSS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Carriers of rare variants in TNS2, a ubiquitously expressed protein-coding gene including in brain, had significantly higher rates of HP deficiencies (rate ratio 2.72 [95% CI 1.81-4.09], P = 1.5 \u00d7 10\u22125) compared to non-carriers, which was replicated in the CCSS. This was also observed in individual HP deficiencies: LH\/FSHD (3.31 [1.28-7.99]), TSHD (5.29 [2.42-11.34]), and ACTHD (3.97 [1.05-12.31]). There were no statistically significant variants in GWAS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>TNS2 may contribute to radiation-induced HP deficiencies. With further validation, screening for TNS2 variants has potential to help identify individuals who would benefit from surveillance and intervention following HP-RT.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/clinem\/dgag080","type":"journal-article","created":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T12:38:55Z","timestamp":1771936735000},"page":"e2018-e2029","source":"Crossref","is-referenced-by-count":0,"title":["Hypothalamic-pituitary deficiency after radiation in childhood cancer survivors is associated with rare variants in\n                    <i>TNS2<\/i>"],"prefix":"10.1210","volume":"111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3340-7096","authenticated-orcid":false,"given":"Tomoko","family":"Yoshida","sequence":"first","affiliation":[{"name":"Department of Epidemiology and Cancer Control, St.Jude Children's Research Hospital , Memphis, TN 38105 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