| Title: | Population Prevalence of the Major Thyroid Cancer-Associated Syndromes |
| Journal: | The Journal of Clinical Endocrinology & Metabolism |
| Published: | 15 Apr 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/40231587/ |
| DOI: | https://doi.org/10.1210/clinem/dgaf236 |
Publication 15941
WARNING: the interactive features of this website use CSS3, which your browser does not support. To use the full features of this website, please update your browser.
Abstract
CONTEXT: Understanding the population prevalence of thyroid cancer-associated syndromes is important to guide germline genetic testing and clinical management.</p>
OBJECTIVE: To estimate the prevalence of the major thyroid cancer-associated syndromes in the United States using data from the All of Us Research Program (All of Us) and the UK Biobank.</p>
DESIGN: 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-associated syndromes defined by the presence of P/LP variants.</p>
RESULTS: Using logistic regression, we found that three hereditary syndromes, multiple endocrine neoplasia type 2 (MEN2, RET gene, p = 3.23e-20), PTEN hamartoma 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-associated syndromes in the All of Us was 1:2,172, 1:8,764, and 1:8,461, and in the UK Biobank, it was 1:2,348, 1:13,043, and 1:8,238 for MEN2, PHTS, and FAP, respectively. Three pathogenic RET variants that cause two 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.</p>
CONCLUSIONS: The prevalence of MEN2 and PHTS is ∼10-20 times higher than it 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.</p>
7 Authors
- Samantha L White
- Taylor Jamil
- Caitlin Bell
- Lauren Fishbein
- Bryan R Haugen
- Christopher R Gignoux
- Nikita Pozdeyev
1 Application
| Application ID | Title |
|---|---|
| 95339 | Genetic architecture of thyroid cancer and its clinical utility. |
Enabling scientific discoveries that improve human health