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2022-RA-1342-ESGO Ethnicity-specific spectrum of BRCA1, BRCA2 and ATM pathogenic variants in ovarian and breast cancer patients from North Caucasus
  1. Evgeny Imyanitov1,
  2. Elvina Bakaeva1,
  3. Alexandr Romanko1,
  4. Ilya Stepanov1,
  5. Luiza Sultanova2,
  6. Zaur Hamgokov3,
  7. Madina Chahkieva4,
  8. Mirza Murachuyev5 and
  9. Anna Sokolenko1
  1. 1N.N. Petrov Institute of Oncology, St.-Petersburg, Russian Federation
  2. 2Chechen Republican Cancer Center, Grozny, Russian Federation
  3. 3Kabardino-Balkarian Republican Cancer Center, Nalchik, Russian Federation
  4. 4Ingushetian Republican Cancer Center, Nazran, Russian Federation
  5. 5Dagestan Republican Cancer Center, Mkhachkala, Russian Federation


Introduction/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.

Methodology This study involved ovarian cancer (OC) and breast cancer (BC) patients from Chechnya (n = 147), Kabardino-Balkaria (n = 139), North Ossetia (n = 83), Ingushetia (n = 88) and Dagestan (n = 137). The entire coding sequences of BRCA1, BRCA2 and ATM genes were analyzed by next-generation sequencing (NGS) in 180 OCs and 414 BCs.

Results Consecutive OC series were characterized by high frequency of BRCA1/2 mutations across all analyzed ethnic groups, ranging from 18% to 33%. BC patients, which were enriched by early-onset, family history-positive and receptor triple-negative disease, showed mutation rate varying from 4% to 14%. There were founder pathogenic alleles in Chechens (BRCA1 c.3629_3630delAG; 10 out of 20 BRCA1/2 mutations) and North Ossetians (BRCA2 c.6341delC; 6 out 10 BRCA1/2 mutations). Interestingly, Chechen BRCA1 c.3629_3630delAG allele was not observed among patients of Ingush ethnicity, despite these nations are believed to have common Nakh (Vainakh) roots. In Ingush patients, there were two recurrent alleles in the BRCA2 gene (c.5351dupA: 5 out 13 BRCA1/2 mutations; L1686X: 3 out 13 mutations). BRCA2 Q3299X mutation was repeatedly observed across several ethnic groups. OC 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.

Conclusion Genetic analysis of non-selected ovarian cancer patients is highly efficient in revealing ethnicity-specific BRCA1/2 mutations. Contribution of BRCA1/2 pathogenic alleles in OC and BC morbidity is high across various ethnic groups. Founder BRCA1/2 alleles are characteristic for some but not all North Caucasus nations.

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