Medullary Thyroid Cancer Risk and Mortality in Carriers of Incidentally Identified MEN2A RET Variants
An erratum to this article was published (JAMA Netw Open, 1 Aug 2025 ↗)
Authors' conclusion
In this cohort study, moderate-risk RET variants were most common in incidental cases. The variants were associated with a substantially lower medullary thyroid cancer risk than clinically ascertained cases. This evidence addresses a current knowledge gap, enabling more informed clinical decision-making.
Study context
- Population
- Clinically unselected individuals with incidentally identified RET germline pathogenic variants (UK Biobank, recruited 2006–2010; Geisinger MyCode, recruited 2004–2020)
- Participants
- 383,914 / 122,640 / 1,078
- Exposure
- Incidentally identified RET variant carriers vs clinically ascertained MEN2 cohort; carriers vs noncarriers for mortality
- UK Biobankn = 383,914
- Geisinger MyCoden = 122,640
- Clinically ascertainedn = 1,078reference
- Outcome
- Frequency and spectrum of pathogenic RET variants, risk of clinically present MTC, and all-cause mortality without thyroidectomy
Methodological detailsclinically unselected population cohorts (UK Biobank; Geisinger MyCode), comparison with clinically ascertained cohort, UK Biobank follow-up to June 2023; Geisinger MyCode follow-up to October 2023
- Clinically unselected population cohorts (UK Biobank; Geisinger MyCode)
- Comparison with clinically ascertained cohort
- UK Biobank follow-up to June 2023; Geisinger MyCode follow-up to October 2023
Main finding
As reported in the abstract
Prevalence of pathogenic RET variant; MTC risk by age 75 years in carriers
| Group | Value | MTC risk by age 75 years (Kaplan-Meier) | MTC risk by age 75 years, matched variants |
|---|---|---|---|
| UK Biobank | 0.04% (CI 0.04%–0.05%) | 2.2% (95% CI, 0.7%-6.9) | |
| Geisinger MyCode | 0.06% (CI 0.05%–0.78%) | 19.3% (95% CI, 6.4%-30.2%) | |
| Clinically ascertained | 95.7% [95% CI, 82.1%-99.7%] |
Value
UK Biobank0.04% (CI 0.04%–0.05%)
Geisinger MyCode0.06% (CI 0.05%–0.78%)
Clinically ascertained— not stated in the abstract
MTC risk by age 75 years (Kaplan-Meier)
UK Biobank2.2% (95% CI, 0.7%-6.9)
Geisinger MyCode19.3% (95% CI, 6.4%-30.2%)
Clinically ascertained— not stated in the abstract
MTC risk by age 75 years, matched variants
UK Biobank— not stated in the abstract
Geisinger MyCode— not stated in the abstract
Clinically ascertained95.7% [95% CI, 82.1%-99.7%]
Observational data: associations, not effects.
Further findings
Spectrum of pathogenic RET variants
- Variants predominantly from the moderate-risk category per ATA guidelines
All-cause mortality without thyroidectomy, UK Biobank · by age 75 years
- Variant carriers who did not undergo thyroidectomy
- 166 [98.2%]
- All-cause mortality, variant carriers
- 6.1% [95% CI, 2.7%-13.8%]
- All-cause mortality, noncarriers
- 5.7% [95% CI, 5.6%-5.8%]
- Mortality similar in carriers and noncarriers, with consistent findings in the US health system cohort
Original publication
Medullary Thyroid Cancer Risk and Mortality in Carriers of Incidentally Identified MEN2A RET Variants. JAMA Netw Open. Published 2 June 2025. doi:10.
Composed by AI from the published abstract and checked against it. How Briefs are made →