Germline Telomere-Regulating Gene Variants Are Not Associated with Thyroid Cancer in a Saudi Arabian Population

<b><i>Background:</i></b> Germline variants in the telomere-regulating genes (TRG) of the shelterin complex have recently been associated with long telomere length and increased risk of several tumors, including thyroid cancer (TC). We aimed to validate these findings in a different ancestral population. <b><i>Patients and Methods:</i></b> We conducted a cross-sectional study in a tertiary care hospital in Saudi Arabia. We included 189 patients with sporadic TC and 63 members of 26 families with at least two members with TC. Whole exome sequencing was performed on genomic DNA isolated from peripheral blood, and bioinformatics analysis focused on TRG variants. <b><i>Results:</i></b> In the 189 sporadic TC patients, 8 TRG variants were found in 39 patients (20.6%). These included 3 <i>ACD</i> variants in 30 patients (NM_001082486.2: c.22G>A, c.617A>C and c.824C>T), 2 variants in <i>TERF1</i> in 4 patients (NM_003218.4: c.162_163insGAG and c.1126C>G) and 3 variants in <i>TERT</i> in 5 patients (NM_198253: c.769G>T, c.76A>G and c.1323_1325del). In 63 patients with a family history of TC (26 families), only two variants were found: a <i>TERF1</i> variant in one patient (NM_017489.3: c.347C>T), and an <i>ACD</i> variant (NM_001082486.2: c.22G>A) in 2 affected members of a 4-member family with papillary TC and in another patient from an unrelated family. All the TRG variants found in this study were either variants of unknown significance or likely benign. The TRG variants described in the recent studies from the United States were absent in the current study and our local database of >18,000 exomes. <b><i>Conclusions:</i></b> Unlike the recently reported results from the United States, TRG variants do not seem to play a role in sporadic or familial TC samples from the Saudi Arabian population. These results suggest that the role of TRG variants may vary among different ethnic populations and call for validation of these findings in diverse populations.