{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:22:42Z","timestamp":1787026962601,"version":"build-2736575974"},"reference-count":27,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T00:00:00Z","timestamp":1776729600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Nutr."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Vitamin D deficiency (VDD) has been implicated as a potential risk factor for thyroid cancer; however, existing evidence is derived primarily from case-control or cross-sectional studies. This study aimed to examine the association between pre-diagnostic VDD and the risk of incident thyroid cancer over a 10-year follow-up period.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This retrospective propensity score\u2013matched cohort study used the TriNetX Global Collaborative Network. Adults aged \u2265 18 y with serum 25-hydroxyvitamin D [25(OH)D] measurements between 2010 and 2023 were classified as having VDD (&amp;lt;20 ng\/mL) or vitamin D sufficiency (\u226530 ng\/mL). One-to-one propensity score matching was performed on demographics, comorbidities, thyroid-related disorders, laboratory values, and vitamin D supplementation. The primary outcome was incident thyroid cancer ascertained \u2265 180 day after the index date (landmark approach) over 10 y of follow-up. Positive (osteoporotic fracture) and negative (appendicitis, goiter) control outcomes and thyroid procedure utilization were evaluated to assess detection bias.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>After matching, 571,669 pairs were analyzed over a median follow-up of 6.8 y. VDD was associated with an increased risk of incident thyroid cancer (HR: 1.41; 95% CI: 1.32, 1.50), and this risk was attenuated among patients with vitamin D insufficiency (25[OH]D 20\u201330 ng\/mL; HR: 1.27; 95% CI: 1.20, 1.34), demonstrating a dose-dependent relationship. Thyroid biopsy and ultrasonography utilization were lower in the VDD cohort (HR: 0.95), arguing against detection bias. The positive control outcome (osteoporotic fracture; HR: 1.53) confirmed the validity of the exposure classification, whereas the negative control (appendicitis; HR: 1.02) showed no association. Findings were robust across all sensitivity and subgroup analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Pre-diagnostic VDD was associated with increased thyroid cancer risk in a dose-dependent manner. These findings support further investigation of vitamin D status as a potentially modifiable risk factor for thyroid cancer.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnut.2026.1817123","type":"journal-article","created":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T04:22:06Z","timestamp":1776745326000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Pre-diagnostic vitamin D deficiency and subsequent thyroid cancer risk: a propensity-matched cohort study"],"prefix":"10.3389","volume":"13","author":[{"given":"Kuo-Chuan","family":"Hung","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Chi Mei Medical Center","place":["Tainan City, Taiwan"]},{"name":"School of Medicine, College of Medicine, National Sun Yat-sen University","place":["Kaohsiung, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia-Li","family":"Kao","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, E-Da Hospital, I-Shou University","place":["Kaohsiung City, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Yew","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Chi Mei Medical Center","place":["Tainan City, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Chen","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Chi Mei Medical Center","place":["Tainan City, Taiwan"]},{"name":"School of Medicine, College of Medicine, National Sun Yat-sen University","place":["Kaohsiung, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I-Wen","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Chi Mei Medical Center, Liouying","place":["Tainan City, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"5173","DOI":"10.3390\/ijms26115173","article-title":"Thyroid Cancer: epidemiology, classification, risk factors, diagnostic and prognostic markers, and current treatment strategies.","volume":"26","author":"Forma","year":"2025","journal-title":"Int J Mol Sci."},{"key":"B2","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1038\/s41574-025-01168-y","article-title":"Unravelling the rise in thyroid cancer incidence and addressing overdiagnosis.","volume":"22","author":"Chen","year":"2026","journal-title":"Nat Rev Endocrinol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"4542","DOI":"10.1002\/cam4.3970","article-title":"The global burden of thyroid cancer and its attributable risk factor in 195 countries and territories: a systematic analysis for the Global Burden of Disease Study.","volume":"10","author":"Zhai","year":"2021","journal-title":"Cancer Med."},{"key":"B4","doi-asserted-by":"publisher","first-page":"6172","DOI":"10.3390\/cancers14246172","article-title":"Thyroid carcinoma: a review for 25 Years of environmental risk factors studies.","volume":"14","author":"Kruger","year":"2022","journal-title":"Cancers."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1210\/endrev\/bnad022","article-title":"Radiation-Related Thyroid Cancer.","volume":"45","author":"Saenko","year":"2024","journal-title":"Endocr Rev."},{"key":"B6","doi-asserted-by":"publisher","first-page":"748","DOI":"10.20945\/2359-3997000000565","article-title":"Vitamin D metabolism and extraskeletal outcomes: an update.","volume":"66","author":"Silva","year":"2022","journal-title":"Arch Endocrinol Metab."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1109","DOI":"10.1210\/er.2018-00126","article-title":"Skeletal and extraskeletal actions of Vitamin D: current evidence and outstanding questions.","volume":"40","author":"Bouillon","year":"2019","journal-title":"Endocr Rev."},{"key":"B8","doi-asserted-by":"publisher","first-page":"4135","DOI":"10.3892\/mmr.2020.11522","article-title":"Vitamin D receptor knockdown attenuates the antiproliferative, pro-apoptotic and anti-invasive effect of vitamin D by activating the Wnt\/\u03b2-catenin signaling pathway in papillary thyroid cancer.","volume":"22","author":"Pang","year":"2020","journal-title":"Mol Med Rep."},{"key":"B9","doi-asserted-by":"publisher","first-page":"5629","DOI":"10.1111\/jcmm.15224","article-title":"Calcitriol enhances Doxorubicin-induced apoptosis in papillary thyroid carcinoma cells via regulating VDR\/PTPN2\/p-STAT3 pathway.","volume":"24","author":"Zhang","year":"2020","journal-title":"J Cell Mol Med."},{"key":"B10","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1530\/ERC-21-0309","article-title":"C\/EBP\u03b2 mediates anti-proliferative effects of 1,25(OH)2D on differentiated thyroid carcinoma cells.","volume":"29","author":"Xu","year":"2022","journal-title":"Endocr Relat Cancer."},{"key":"B11","doi-asserted-by":"publisher","first-page":"3516","DOI":"10.3390\/cancers13143516","article-title":"The role of vitamin d as a prognostic marker in papillary Thyroid Cancer.","volume":"13","author":"Bains","year":"2021","journal-title":"Cancers."},{"key":"B12","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1016\/j.nut.2018.04.015","article-title":"Vitamin D deficiency as a risk factor for thyroid cancer: a meta-analysis of case-control studies.","volume":"57","author":"Zhao","year":"2019","journal-title":"Nutrition."},{"key":"B13","doi-asserted-by":"publisher","first-page":"1199","DOI":"10.1007\/s40618-018-0853-9","article-title":"Association between vitamin D deficiency and risk of thyroid cancer: a case-control study and a meta-analysis.","volume":"41","author":"Hu","year":"2018","journal-title":"J Endocrinol Invest."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1423305","DOI":"10.3389\/fnut.2024.1423305","article-title":"Association between vitamin D status and thyroid cancer: a meta-analysis.","volume":"11","author":"Hu","year":"2024","journal-title":"Front Nutr."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1602844","DOI":"10.3389\/fendo.2025.1602844","article-title":"Association between vitamin D serum levels and thyroid cancer: a meta-analysis.","volume":"16","author":"Yang","year":"2025","journal-title":"Front Endocrinol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"e0164550","DOI":"10.1371\/journal.pone.0164550","article-title":"25-Hydroxyvitamin D and TSH as risk factors or prognostic markers in thyroid carcinoma.","volume":"11","author":"Danilovic","year":"2016","journal-title":"PLoS One."},{"key":"B17","doi-asserted-by":"publisher","first-page":"102","DOI":"10.3904\/kjim.2015.090","article-title":"Serum vitamin D3 levels are not associated with thyroid cancer prevalence in euthyroid subjects without autoimmune thyroid disease.","volume":"32","author":"Choi","year":"2017","journal-title":"Korean J Intern Med."},{"key":"B18","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1308\/rcsann.2024.0041","article-title":"Vitamin D deficiency and thyroid cancer: is there a true association? A prospective observational study.","volume":"107","author":"Lanitis","year":"2025","journal-title":"Ann R Coll Surg Engl."},{"key":"B19","doi-asserted-by":"publisher","first-page":"11173","DOI":"10.2147\/DDDT.S569143","article-title":"Perioperative ketamine exposure and postoperative atrial fibrillation\/flutter risk after video-assisted thoracoscopic surgery: a multi-institutional study.","volume":"19","author":"Hung","year":"2025","journal-title":"Drug Des Devel Ther."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1707271","DOI":"10.3389\/fnut.2025.1707271","article-title":"Prognostic role of baseline hemoglobin level for long-term mortality in newly diagnosed rheumatoid arthritis: a cohort study.","volume":"12","author":"Chen","year":"2025","journal-title":"Front Nutr."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1666887","DOI":"10.3389\/fnut.2025.1666887","article-title":"Association of zinc deficiency and risk of new-onset dementia: a retrospective cohort study.","volume":"12","author":"Huang","year":"2025","journal-title":"Front Nutr."},{"key":"B22","doi-asserted-by":"publisher","first-page":"5092","DOI":"10.1007\/s11695-025-08290-w","article-title":"Association between sugammadex use and risk of postoperative urinary complications after metabolic and bariatric surgery: a multi-institutional study.","volume":"35","author":"Ko","year":"2025","journal-title":"Obes Surg."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1248","DOI":"10.3390\/nu12051248","article-title":"Vitamin D\u2019s effect on immune function.","volume":"12","author":"Martens","year":"2020","journal-title":"Nutrients."},{"key":"B24","doi-asserted-by":"publisher","first-page":"599623","DOI":"10.3389\/fimmu.2020.599623","article-title":"Vitamin D3-Induced tolerogenic dendritic cells modulate the transcriptomic profile of T CD4+ Cells towards a functional hyporesponsiveness.","volume":"11","author":"Navarro-Barriuso","year":"2020","journal-title":"Front Immunol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1007\/s12026-018-9033-4","article-title":"1,25-Dihydroxyvitamin D3 modulates T cell differentiation and impacts on the production of cytokines from Chinese Han patients with early rheumatoid arthritis.","volume":"67","author":"Wen","year":"2019","journal-title":"Immunol Res."},{"key":"B26","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1186\/s13044-021-00117-x","article-title":"Is Hashimoto thyroiditis associated with increasing risk of thyroid malignancies? A systematic review and meta-analysis.","volume":"14","author":"Abbasgholizadeh","year":"2021","journal-title":"Thyroid Res."},{"key":"B27","doi-asserted-by":"publisher","first-page":"153098","DOI":"10.1016\/j.prp.2020.153098","article-title":"Thyroid cancer and thyroid autoimmune disease: a review of molecular aspects and clinical outcomes.","volume":"216","author":"Dias Lopes","year":"2020","journal-title":"Pathol Res Pract."}],"container-title":["Frontiers in Nutrition"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2026.1817123\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T04:22:06Z","timestamp":1776745326000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2026.1817123\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,21]]},"references-count":27,"alternative-id":["10.3389\/fnut.2026.1817123"],"URL":"https:\/\/doi.org\/10.3389\/fnut.2026.1817123","relation":{},"ISSN":["2296-861X"],"issn-type":[{"value":"2296-861X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,21]]},"article-number":"1817123"}}