Abstract 2P
Background
North Caucasus hosts several large ethnic groups, which preserved their national identity through the course of history. These populations are likely to have a unique pattern of disease-predisposing alleles reflecting the genetic background of their ancestors.
Methods
This study involved 180 ovarian cancer (OC) patients from Chechnya (n = 68), Kabardino-Balkaria (n = 49), North Ossetia (n = 32), Ingushetia (n = 16) and Dagestan (n = 15). The entire coding sequences of BRCA1, BRCA2, ATM and PALB2 genes were analyzed by next-generation sequencing.
Results
OC patients belonging to various ethnic groups had high frequency of BRCA1/2 mutations ranging from 18% to 33%. There were founder pathogenic alleles detected in Chechens (BRCA1 c.3629_3630delAG; 9 out of 15 BRCA1/2 mutations) and North Ossetians (BRCA2 c.6341delC; 6 out 8 BRCA1/2 mutations). Interestingly, Chechen BRCA1 c.3629_3630delAG allele was not present among patients of Ingush ethnicity, despite these nations are believed to have common roots. BRCA2 Q3299X mutation was repeatedly observed across several ethnic groups. Patients from Kabardino-Balkaria had unusually high frequency of germ-line ATM truncating alleles (3/49, 6%); all 3 ATM mutations were represented by distinct ATM pathogenic variants. There were no instances of PALB2 germ-line mutations.
Conclusions
Genetic analysis of ovarian cancer patients is efficient in revealing ethnicity-specific BRCA1/2 mutations. Contribution of BRCA1/2 pathogenic alleles in OC morbidity is high across various ethnic groups. Founder BRCA1/2 alleles are characteristic for some but not all North Caucasus nations.
Legal entity responsible for the study
The authors.
Funding
This study has been supported by the Russian Science Foundation, grant 21-75-30015.
Disclosure
All authors have declared no conflicts of interest.