Medullary Thyroid Cancer Risk and Mortality in Carriers of Incidentally Identified MEN2A RET Variants

作者：C West, Uyenlinh L. Mirshahi, Katherine S. Ruth, Luke N Sharp, Ankit M Arni, Clare Turnbull, Caroline F. Wright, Bijay Vaidya, Martina Owens, David J. Carey, Kashyap Patel · 发表于：JAMA Network Open · 年份：2025 · DOI：10.1001/jamanetworkopen.2025.17937 · 被引用次数：9 · 研究领域：Thyroid Cancer Diagnosis and Treatment、Thyroid Disorders and Treatments、Neuroendocrine Tumor Research Advances

Importance: RET germline pathogenic variants cause multiple endocrine neoplasia type 2 (MEN2), which is associated with medullary thyroid cancer. With increasing incidental identification of these variants in asymptomatic individuals outside family screening, these individuals' risk of medullary thyroid cancer and all-cause mortality without intervention remain unknown in this context. Objective: To evaluate the risk of medullary thyroid cancer and all-cause mortality in clinically unselected individuals with incidentally identified RET variants and assess whether the risk of medullary thyroid cancer differs from those with clinically ascertained RET variants. Design, Setting, and Participants: This prospective cohort study of 383 914 unrelated individuals from the clinically unselected UK population (UK Biobank, recruited in 2006-2010, with follow-up to June 2023) and 122 640 unrelated individuals from a US health system (Geisinger MyCode cohort, recruited 2004-2020, with follow-up to October 2023) compared medullary thyroid cancer risk in these cohorts with 1078 individuals who were clinically ascertained with suspicion of MEN2 from a UK routine practice. Exposures: RET germline pathogenic variants causing MEN2. Main Outcomes and Measures: Frequency and the spectrum of pathogenic RET variants, risk of clinically present medullary thyroid cancer, and all-cause mortality without thyroidectomy were assessed using proportions with exact binomial 95% CIs and survival analysis ad...