2022-RA-1342-ESGO Ethnicity-specific spectrum of BRCA1, BRCA2 and ATM pathogenic variants in ovarian and breast cancer patients from North Caucasus. (20th October 2022)

• Record Type: Journal Article
• Authors: Imyanitov, Evgeny; Bakaeva, Elvina; Romanko, Alexandr; Stepanov, Ilya; Sultanova, Luiza; Hamgokov, Zaur; Chahkieva, Madina; Murachuyev, Mirza; Sokolenko, Anna
• Is Part Of: International journal of gynecological cancer. Volume 32(2022)Supplement 2
• Page Start: A415
• Page End: A416
• Publication Date: 2022-10-20
• Subjects: Generative organs, Female -- Cancer -- Periodicals; 616.99465
• DOI: 10.1136/ijgc-2022-ESGO.890
• Languages: English
• ISSNs: 1048-891X

Abstract

Abstract : 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.