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. 2022 May;193(1):217-224.
doi: 10.1007/s10549-022-06557-9. Epub 2022 Mar 12.

Common founder BRCA2 pathogenic variants and breast cancer characteristics in Ethiopian Jews

S Lieberman  1 , R Chen-Shtoyerman  2 , Z Levi  3   4 , S Shkedi-Rafid  5   6 , S Zuckerman  7 , R Bernstein-Molho  3   8 , G Reznick Levi  9 , S S Shachar  3   10 , A Flugelman  11   12 , V Libman  13 , I Kedar  14 , S Naftaly-Nathan  14 , I Lagovsky  14 , T Peretz  6   15 , N Karminsky  16 , S Carmi  17 , E Levy-Lahad  7   6 , Y Goldberg  3   14
Affiliations

Common founder BRCA2 pathogenic variants and breast cancer characteristics in Ethiopian Jews

S Lieberman et al. Breast Cancer Res Treat. 2022 May.

Abstract

Purpose: BRCA1/2 founder pathogenic variants (PVs) occur in various populations, but data on the mutational spectrum in Africans are limited. We examined BRCA1/2 PVs in breast cancer patients of Ethiopian Jewish (EJ) origin.

Methods: We retrospectively analyzed BRCA1/2 test results and clinical features of EJ breast cancer patients from seven medical institutions. We obtained heterozygote carrier rates in affected individuals from the laboratories of the largest Israeli HMO (Clalit). Population carrier frequency was determined in EJ controls.

Results: We identified three recurrent BRCA2 PVs in 11 EJ breast cancer patients (9 females, 2 males): c.7579delG, c.5159C > A, and c.9693delA. Only c.5159C > A was previously reported in Africans. In women, mean age at diagnosis was 35.7y; 8/9 were diagnosed with advanced disease. All tumors were invasive, 4/9 were triple negative. Only 3/11 carriers had relevant family history. Carrier rate in high-risk breast cancer patients was 11% (3/28; 95%CI [2.3%, 28.2%]). Combined carrier rate among controls was 1.8% (5/280; 95%CI [0.6%, 4.1%]).

Conclusion: EJs harbor 3 recurrent BRCA2 PVs presenting with relatively severe breast cancer morbidity. Combined with the high BRCA2 carrier rate in the EJ population, these findings merit increasing awareness in this community and suggest that a culturally adapted population screening approach may be warranted.

Keywords: BRCA2; Breast cancer; Ethiopian Jews; Founder mutations.

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References

    1. Gabai-Kapara E, Lahad A, Kaufman, et al (2014) Population-based screening for breast and ovarian cancer risk due to BRCA1 and BRCA2. Proc Natl Acad Sci U S A 30:14205–14210. https://doi.org/10.1073/pnas.1415979111 - DOI
    1. Nelson HD, Pappas M, Cantor A, Haney E, Holmes R (2019) Risk Assessment, genetic counseling, and genetic testing for BRCA-Related Cancer in Women: updated evidence report and systematic review for the us preventive services task force. JAMA 322(7):666–685. https://doi.org/10.1001/jama.2019.8430 - DOI - PubMed
    1. Tutt ANJ, Garber JE, Kaufman B et al (2021) Adjuvant Olaparib for Patients with BRCA1- or BRCA2-Mutated Breast Cancer. N Engl J Med 24:2394–2405. https://doi.org/10.1056/NEJMoa2105215 - DOI
    1. Jiang Y, Meng XY, Deng NN et al (2021) Effect and safety of therapeutic regimens for patients with germline BRCA mutation-associated breast cancer: a network meta-analysis. Front Oncol 20:718761. https://doi.org/10.3389/fonc.2021.718761 - DOI
    1. Friebel TM, Andrulis IL, Balmaña J et al (2019) BRCA1 and BRCA2 pathogenic sequence variants in women of African origin or ancestry. Hum Mutat 40:1781–1796. https://doi.org/10.1002/humu.23804 - DOI - PubMed - PMC

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