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

Abstract

Purpose: Individuals with thyroid cancer have the highest prevalence of clonal hematopoiesis (CH) among patients with cancer. We sought to determine whether individuals who later develop thyroid cancer more frequently have CH before diagnosis or germline cancer susceptibility than healthy controls.

Methods: We conducted a retrospective case-control study using subjects enrolled between 2002 and 2015 in a population-based biobank. Cases were healthy at enrollment but subsequently developed an incident thyroid cancer. Controls were healthy age- and race-matched subjects who were never diagnosed with a cancer. To assess baseline CH, whole-exome sequencing (WES) was performed on peripheral blood (PB) DNAs collected at enrollment. To assess CH acquisition over time, we recontacted a subset of cases and controls approximately 20 years after initial sampling for repeat PB WES.

Results: At enrollment, on average 9 years before a thyroid cancer diagnosis for cases, we identified CH in three of 63 (5%) cases and four of 125 (3%) controls. Adjusting for age, sex, and race, those with CH had a 1.51 odds (0.31-7.33; P = .61) of a thyroid cancer diagnosis versus those without CH at baseline. We detected pathogenic germline cancer susceptibility variants in 11% of cases and 7% of controls (P = .44). Among seven cases and seven controls recontacted, we found incident CH development in three (43%) and two (29%), respectively.

Conclusion: We found that individuals who later develop early-stage thyroid cancers do not have a significantly higher prevalence of CH years before their diagnosis nor carry germline cancer susceptibility variants more often than those who do not develop thyroid cancer. Larger longitudinal studies are needed to fully elucidate the impact of germline and exposures in CH etiology.