Obesity, Obesity-related Metabolic Conditions, and Risk of Thyroid Cancer in Women: Results from a Prospective Cohort Study (Sister Study)

Background: Thyroid cancer incidence has increased worldwide. Obesity trends may play a role, but the underlying biological pathways are not well-characterized. Therefore, we examined associations of excess adiposity and obesity-related metabolic conditions with thyroid cancer incidence.

Methods: From the Sister Study, a cohort of sisters of women with breast cancer, we included 47,739 women who were cancer-free at baseline (2003-2009). Height, weight, waist and hip circumference, and blood pressure were measured at baseline and medical history was self-reported. Cox proportional hazards regression models were adjusted for age (time scale), race/ethnicity, smoking, baseline history of benign thyroid disease, and frequency of routine healthcare visits.

Findings: During follow-up (median = 12.5; max = 15.9 years), 259 women reported incident thyroid cancer. Body mass index (BMI) (hazard ratio [HR] = 1.25, 95% CI = 1.14-1.37), waist circumference (HR = 1.11, 95% CI = 1.06-1.15), and waist-to-hip ratio (HR  = 1.49, 95% CI = 1.14-1.94) were positively associated with thyroid cancer incidence, as were metabolic syndrome (HR = 1.67, 95% CI = 1.24-2.25), dyslipidemia (HR = 1.46, 95% CI = 1.13-1.90), borderline diabetes (HR = 2.06, 95% CI = 1.15-3.69), hypertension (HR = 1.49, 95% CI = 1.12-1.96), and polycystic ovary syndrome (PCOS, HR = 2.10, 95% CI = 1.20-3.67). These associations were attenuated with additional BMI adjustment, although dyslipidemia (HR = 1.35, 95% CI = 1.04-1.75) and PCOS (HR = 1.86, 95% CI = 1.06-3.28) remained associated with thyroid cancer incidence. Hypothyroidism was not associated with thyroid cancer.

Interpretation: In this cohort of sisters of women diagnosed with breast cancer, excess adiposity and several obesity-related metabolic conditions were associated with thyroid cancer incidence. These findings provide insights into potential biological mechanisms linking obesity and thyroid cancer.

Funding: This research was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute and National Institute of Environmental Health Sciences (Z01-ES044005).