Genetic predisposition to differentiated thyroid cancer among Polish population.

INTRODUCTION: The genome sequencing technologies reveal the molecular mechanisms of differentiated thyroid cancer (DTC). Unlike somatic mutation analysis from thyroidectomy samples, germline mutations showing genetic susceptibility to DTC are less understood.

OBJECTIVES: The study aimed to assess the prevalence of germline mutations predisposing to DTC in a cohort of Polish individuals based on their whole genome sequencing (WGS) data.

PATIENTS AND METHODS: We analyzed sequencing data from 1076 unrelated individuals totaling over 1018 billion read pairs and yielding an average 35.26× read depth per genome, released openly for academic and clinical research as The Thousand Polish Genomes database (https://1000polishgenomes.com). The list of genes chosen for further analysis was based on the review of previous studies.

RESULTS: The cohort contained 104 variants located within the coding and noncoding DNA sequences of 90 genes selected by ClinVar classification as pathogenic and potentially pathogenic. The frequency of variants in the Polish cohort (our study) was compared to the frequency estimated for the non-Finnish European population, obtained from the gnomAD database (gnomad.broadinstitute.org). Statistically significant variants included APC, ARSB, ATM, BRCA1, CHEK2, DICER1, GPD1L, INSR, KCNJ10, MYH9, PALB2, PLCB1, PLEKHG5, PTEN, RET, SEC23B, SERPINA1, SLC26A4, SMAD3, STK11, TERT, TOE1, and WRN genes.

CONCLUSIONS: Even though the Polish population is genetically similar to other European populations, there are significant differences in variant frequencies contributing to the disease development and progression, such as RET, CHEK2, BRCA1, SLC26A4 or TERT. Further studies are needed to identify genomic variants associated directly with DTC.