Association Between Zinc Deficiency and Risk of Thyroid Cancer: A Multi-Institutional Cohort Study

Abstract Zinc plays a critical role in thyroid hormone metabolism and antioxidant defense, yet its relationship with thyroid cancer remains unclear due to limited and inconsistent evidence from predominantly cross-sectional studies. We conducted a large-scale retrospective cohort study using the TriNetX Research Network to examine the longitudinal association between zinc deficiency (ZD) and thyroid cancer risk over ten years. Among 96,497 propensity score-matched pairs of adults who underwent serum zinc measurements between January 2010 and December 2023, we classified patients as zinc-deficient (serum zinc below 70 μg/dL) or having normal zinc status (70–120 μg/dL), controlling for demographics, comorbidities, preexisting thyroid disorders, and laboratory parameters. While the overall cohort showed no significant association between ZD and thyroid cancer at 5 years (hazard ratio [HR]: 1.13, 95% confidence interval (CI): 0.93–1.37) or 10 years (HR: 1.12, 95% CI: 0.93–1.34), sex-stratified analyses revealed that women with ZD demonstrated significantly increased thyroid cancer risk at both 5 years (HR: 1.37, 95% CI: 1.09–1.72) and 10 years (HR: 1.38, 95% CI: 1.12–1.71), while men showed no association. These findings suggest that ZD may represent a sex-specific modifiable risk factor for thyroid cancer in women, warranting further mechanistic investigation.