Effect of Genetic Ancestry on Phenotypes and Genotypes in Papillary Thyroid Cancer

Thyroid cancer (THCA) is a prevalent health burden, and unpacking its biological and social determinants is a public health priority. Previous studies have reported inconsistent findings regarding the effects of race and ethnicity on the incidence and presentation of THCA. It remains unclear whether racial differences manifest at the molecular level. By harnessing the Cancer Genome Atlas papillary THCA dataset, this study derived genetic ancestry estimates from single nucleotide polymorphism array genotyping and exome sequencing data. Five ancestral groups (Europeans, East Asians, Africans, Native/Latin Americans, and South Asians) were included for analysis. We found a good agreement between genetic ancestry and reported race (Cramer's V = 0.730). Although differences in tumor size and patient age were observed, overall survival, progression-free interval, and disease-free interval were similar across the ancestral groups. Furthermore, the distribution of oncogenic drivers did not significantly differ among these groups. Weighted gene co-expression network analysis identified several ancestry-associated signatures. In conclusion, this study suggests that hereditary ancestral traits likely have little biological significance in papillary THCA. Instead, racial disparities in this type of cancer may be attributed to lifestyle factors, environmental exposures, and social and political power asymmetries in society and healthcare infrastructure.