Clonal Hematopoiesis Prevalence Years Before a Thyroid Cancer Diagnosis: A Case-Control Study

Area of Science:

• Hematology
• Oncology
• Genetics

Background:

• Thyroid cancer exhibits a high prevalence of clonal hematopoiesis (CH) among cancer patients.
• Understanding the role of CH and germline susceptibility in thyroid cancer development is crucial.

Purpose of the Study:

• To investigate if individuals developing thyroid cancer have a higher prevalence of CH or germline cancer susceptibility before diagnosis compared to healthy controls.
• To assess the longitudinal development of CH in individuals who later develop thyroid cancer.

Main Methods:

• Retrospective case-control study using a population-based biobank (2002-2015).
• Whole-exome sequencing (WES) of peripheral blood DNA at enrollment and approximately 20 years later for a subset.
• Cases developed thyroid cancer post-enrollment; controls remained cancer-free.

Main Results:

• At enrollment (9 years pre-diagnosis), CH prevalence was similar: 5% in cases vs. 3% in controls (P=.61).
• Germline cancer susceptibility variants were found in 11% of cases and 7% of controls (P=.44).
• Incident CH developed in 43% of cases and 29% of controls in the longitudinal follow-up.

Conclusions:

• Individuals who later develop thyroid cancer do not show significantly higher CH prevalence or germline susceptibility years before diagnosis.
• Larger longitudinal studies are required to clarify the role of germline factors and exposures in CH etiology for thyroid cancer.