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18.10.2023 | Epidemiology

Ethnicity-specific BRCA1, BRCA2, PALB2, and ATM pathogenic alleles in breast and ovarian cancer patients from the North Caucasus

verfasst von: Anna P. Sokolenko, Elvina Kh. Bakaeva, Aigul R. Venina, Ekaterina Sh. Kuligina, Alexandr A. Romanko, Svetlana N. Aleksakhina, Yana V. Belysheva, Evgeniya V. Belogubova, Ilya A. Stepanov, Olga A. Zaitseva, Olga S. Yatsuk, Alexandr V. Togo, Zaur M. Khamgokov, Azinat O. Kadyrova, Albert Sh. Pirmagomedov, Marina B. Bolieva, Alexandr A. Epkhiev, Aslan K. Tsutsaev, Madina D. Chakhieva, Khalimat M. Khabrieva, Idris M. Khabriev, Mirza A. Murachuev, Bella N. Buttaeva, Liliya S. Baboshkina, Fatima I. Bayramkulova, Islam R. Katchiev, Lina Kh. Alieva, Grigory A. Raskin, Sergey V. Orlov, Zarema K. Khachmamuk, Karine R. Levonyan, Dariya M. Gichko, Dmitriy V. Kirtbaya, Alexey M. Degtyariov, Luisa V. Sultanova, Hedi S. Musayeva, Alexey M. Belyaev, Evgeny N. Imyanitov

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 2/2024

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Abstract

Background

Mountain areas of the North Caucasus host several large ethnic communities that have preserved their national identity over the centuries.

Methods

This study involved high-grade serous ovarian cancer (HGSOC) and breast cancer (BC) patients from Dagestan (HGSOC: 37; BC: 198), Kabardino-Balkaria (HGSOC: 68; BC: 155), North Ossetia (HGSOC: 51; BC: 104), Chechnya (HGSOC: 68; BC: 79), Ingushetia (HGSOC: 19; BC: 103), Karachay-Cherkessia (HGSOC: 13; BC: 47), and several Armenian settlements (HGSOC: 16; BC: 101). The group of BC patients was enriched by young-onset and/or family history-positive and/or bilateral and/or receptor triple-negative cases. The entire coding region of BRCA1, BRCA2, PALB2, and ATM genes was analyzed by next-generation sequencing.

Results

A significant contribution of BRCA1/2 pathogenic variants (PVs) to HGSOC and BC development was observed across all North Caucasus regions (HGSOC: 19–39%; BC: 6–13%). Founder alleles were identified in all ethnic groups studied, e.g., BRCA1 c.3629_3630delAG in Chechens, BRCA2 c.6341delC in North Ossetians, BRCA2 c.5351dupA in Ingush, and BRCA1 c.2907_2910delTAAA in Karachays. Some BRCA1/2 alleles, particularly BRCA2 c.9895C > T, were shared by several nationalities. ATM PVs were detected in 14 patients, with c.1673delG and c.8876_8879delACTG alleles occurring twice each. PALB2 heterozygosity was observed in 5 subjects, with one variant seen in 2 unrelated women.

Conclusion

This study adds to the evidence for the global-wide contribution of BRCA1/2 genes to HGSOC and BC morbidity, although the spectrum of their PVs is a subject of ethnicity-specific variations. The data on founder BRCA1/2 alleles may be considered when adjusting the BRCA1/2 testing procedure to the ethnic origin of patients.

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Titel: Ethnicity-specific BRCA1, BRCA2, PALB2, and ATM pathogenic alleles in breast and ovarian cancer patients from the North Caucasus
verfasst von: Anna P. Sokolenko
Elvina Kh. Bakaeva
Aigul R. Venina
Ekaterina Sh. Kuligina
Alexandr A. Romanko
Svetlana N. Aleksakhina
Yana V. Belysheva
Evgeniya V. Belogubova
Ilya A. Stepanov
Olga A. Zaitseva
Olga S. Yatsuk
Alexandr V. Togo
Zaur M. Khamgokov
Azinat O. Kadyrova
Albert Sh. Pirmagomedov
Marina B. Bolieva
Alexandr A. Epkhiev
Aslan K. Tsutsaev
Madina D. Chakhieva
Khalimat M. Khabrieva
Idris M. Khabriev
Mirza A. Murachuev
Bella N. Buttaeva
Liliya S. Baboshkina
Fatima I. Bayramkulova
Islam R. Katchiev
Lina Kh. Alieva
Grigory A. Raskin
Sergey V. Orlov
Zarema K. Khachmamuk
Karine R. Levonyan
Dariya M. Gichko
Dmitriy V. Kirtbaya
Alexey M. Degtyariov
Luisa V. Sultanova
Hedi S. Musayeva
Alexey M. Belyaev
Evgeny N. Imyanitov
Publikationsdatum: 18.10.2023
Verlag: Springer US
Erschienen in: Breast Cancer Research and Treatment / Ausgabe 2/2024
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-023-07135-3

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Ethnicity-specific BRCA1, BRCA2, PALB2, and ATM pathogenic alleles in breast and ovarian cancer patients from the North Caucasus