The Journal of clinical endocrinology and metabolism · 2025
Population Prevalence of the Major Thyroid Cancer-Associated Syndromes.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
White Samantha Lee, Jamil Taylor, Bell Caitlin, Fishbein Lauren, Haugen Bryan Roland, Gignoux Christopher Raymond, Pozdeyev Nikita
Аннотация
CONTEXT: Understanding the population prevalence of thyroid cancer-associated syndromes is important to guide germline genetic testing and clinical management.
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.
METHODS: 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.
RESULTS: 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-associated 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.
CONCLUSION: The prevalence of MEN2 and PHTS is ∼10 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.
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.
METHODS: 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.
RESULTS: 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-associated 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.
CONCLUSION: The prevalence of MEN2 and PHTS is ∼10 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.