S Lieberman1, R Chen-Shtoyerman2, Z Levi3,4, S Shkedi-Rafid5,6, S Zuckerman7, R Bernstein-Molho3,8, G Reznick Levi9, S S Shachar3,10, A Flugelman11,12, V Libman13, I Kedar14, S Naftaly-Nathan14, I Lagovsky14, T Peretz6,15, N Karminsky16, S Carmi17, E Levy-Lahad7,6, Y Goldberg3,14. 1. Medical Genetics Institute, Shaare Zedek Medical Center, Jerusalem, Israel. sari@szmc.org.il. 2. The Genetic Institute, Kaplan Medical Center, Rehovot, Israel. 3. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. 4. Division of Gastroenterology, Rabin Medical Center, Petah Tikva, Israel. 5. Department of Genetics, Hadassah Medical Organization, Jerusalem, Israel. 6. Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel. 7. Medical Genetics Institute, Shaare Zedek Medical Center, Jerusalem, Israel. 8. Susanne Levy Gertner Oncogenetics Unit, The Danek Gertner Institute of Human Genetics, Chaim Sheba Medical Center, Tel-Hashomer, Israel. 9. The Genetics Institute, Rambam Health Care Campus, Haifa, Israel. 10. Department of Oncology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. 11. Preventive Medicine Center, Rambam Health Care Campus, Haifa, Israel. 12. Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel. 13. Genetics Institute, Shamir Medical Center, Zerifin, Israel. 14. Rabin Medical Center, Raphael Recanati Genetic Institute, Petach Tikva, Israel. 15. Sharett Institute of Oncology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel. 16. Oncology Department, Wolfson Medical Center, Holon, Israel. 17. Braun School of Public Health and Community Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
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.
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.
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