Early-pregnancy sex steroid and thyroid function hormones, thyroid autoimmunity, and maternal papillary thyroid cancer incidence in the Finnish Maternity Cohort

Abstract

Abstract

Thyroid cancer more commonly affects women than men and is the third most frequently diagnosed cancer among women of reproductive age. We conducted a nested case–control study within the Finnish Maternity Cohort to evaluate pre-diagnostic sex steroid and thyroid function markers in relation to subsequent maternal papillary thyroid cancer. Cases (n = 605) were women ages 18–44 years, who provided an early-pregnancy (<20 weeks gestation) blood sample and were diagnosed with papillary thyroid cancer up to 11 years afterward. Controls (n = 1185) were matched to cases 2:1 by gestational age, mother's age, and date at blood draw. Odds ratios (ORs) for the associations of serum thyroid peroxidase antibodies (TPO-Ab), thyroglobulin antibodies (Tg-Ab), thyroid stimulating hormone (TSH), free thyroxine (fT4), free triiodothyronine (fT3), progesterone, and estradiol with papillary thyroid cancer were estimated using conditional logistic regression. TPO-Ab and Tg-Ab positivity (>95th percentile among controls) were associated with more than 3-fold (OR = 3.32, 95% confidence interval [CI] 2.33–4.72) and 2-fold (OR = 2.03, 95% CI 1.41–2.93) increased odds of papillary thyroid cancer, respectively. These associations were similar by time since blood draw, parity, gestational age, smoking status, and age and stage at diagnosis. In models excluding TPO-Ab or Tg-Ab positivity, TPO-Ab (quartile 4 vs. 1: OR = 1.66, 95% CI 1.17–2.37, p-trend = .002) and Tg-Ab (quartile 4 vs. 1: OR = 1.74, 95% CI 1.22–2.49, p-trend = .01) levels were positively associated with papillary thyroid cancer. No associations were observed for estradiol, progesterone, TSH, fT3, or fT4 overall. Our results suggest that thyroid autoimmunity in early pregnancy may increase the risk of maternal papillary thyroid cancer.