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 obesityrelated 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] (per-5 kg/m)2 = 1.25, 95% CI = 1.14-1.37), waist circumference (HRper- 5 cm increase = 1.11, 95% CI = 1.06-1.15), and waist-to-hip ratio (HR (>= 0.85-versus-<0.85) = 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 obesityrelated metabolic conditions were associated with thyroid cancer incidence. These findings provide insights into potential biological mechanisms linking obesity and thyroid cancer.