Introduction/Background Tatarstan and Bashkortostan are large republics located nearby Volga river. Although they joined Russia about five hundred years ago, they managed to preserve national authenticity over centuries.
Methodology The study included 132 ovarian cancer (OC) patients and 277 women with breast cancer (BC), who reside in Tatarstan or Bashkortostan and identify themselves as ethnic Tatars or Bashkirs. In order to enrich the analyzed groups by carriers of cancer-predisposing pathogenic variants (PVs), OC were selected on the basis of high-grade serous histology, and BC were represented mainly by early-onset and/or family-history positive and/or bilateral and/or receptor triple-negative cases. Coding sequences and 5’- and 3’-UTRs of BRCA1, BRCA2, PALB2, ATM and TP53 genes were analyzed by next generation sequencing.
Results The frequency of BRCA1/2 mutations was 25/132 (19%) in OC and 43/277 (16%) in BC. BRCA1 PVs accounted for 47/68 (69%) cases with mutation. A significant share of BRCA1 PVs detected in ethnic Tatars and Bashkirs was represented by Slavic founder alleles (c.5266dupC (5382insC): n = 14; C61G: n = 4; c.3700_3704delGTAAA: n = 3; c.4034delA: n = 2; c.3756_3759del: n = 1). Seven patients carried BRCA1 c.5161C>T [Q1721X] allele, which is an ethnicity-specific mutation characteristic for this region. There were two recurrent BRCA2 PVs, c.-39–1_-39delGA (n = 6) and c.468dupT (n = 4). One patient carried PV in PALB2 (c.221delA). No instances of ATM or TP53 heterozygosity was observed.
Conclusion Despite well-preserved national identity of Tatars and Bashkirs, Slavic BRCA1 founder PVs are common among patients from these ethnic groups. In addition, one BRCA1 and two BRCA2 ethnicity-specific PVs were identified in this study. Recurrent BRCA2 c.-39–1_-39delGA allele deserves particular attention, because it is located not in coding but in regulatory region of the gene.
Disclosures The study has been supported by the Russian Science Foundation [grant number 21–75-30015].
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