Familial Aggregation and Heritability of Nonmedullary Thyroid Cancer in an Asian Population: A Nationwide Cohort Study

Abstract

Purpose: The purpose of this work is to assess the extent of familial aggregation of nonmedullary thyroid cancer (NMTC) and the relative risks (RRs) of chronic thyroid diseases and common malignancies in first-degree relatives of NMTC patients.

Methods: In the National Health Insurance Research database of Taiwan, all eligible individuals in 2016 were analyzed (n = 23 696 659) and the family structures of 38 686 patients diagnosed with NMTC between 1997 and 2016 were identified. The prevalence and RRs of NMTC, chronic thyroid diseases, and common malignancies in individuals with first-degree relatives with NMTC were examined. The accountability of heritability and environmental factors to NMTC susceptibility was estimated using the polygenic liability model.

Results: The prevalence of NMTC was 0.16% in the general population and 0.64% in individuals with first-degree relatives with NMTC. Regarding affected relatives, the RR (95% CI) for NMTC was 20.12 (4.86-83.29) for twins, 6.43 (4.80-8.62) for siblings, 5.24 (4.55-6.03) for offspring, 5.07 (4.41-5.81) for parents, and 2.07 (1.53-2.81) for spouses. The estimated genetic, common environmental, and nonshared environmental contributions to NMTC were 28.0%, 14.3%, and 57.7%, respectively. A family history of NMTC was associated with higher risks of thyroid nodules (RR, 2.26; 95% CI, 2.18-2.35), Hashimoto thyroiditis (2.11; 1.89-2.36), Graves disease (1.49; 1.42-1.57), lung cancer (1.56; 1.32-1.85), and leukemia and lymphoma (1.24; 1.03-1.50).

Conclusion: Our findings demonstrate the importance of genetic and environmental contributions to NMTC susceptibility and highlight the coaggregation of chronic thyroid diseases and multiple malignancies with NMTC.

Keywords: Graves disease; Hashimoto thyroiditis; familial risk; heritability; nonmedullary thyroid cancer.