Rinat Bernstein-Molho1,2, Inbal Barnes-Kedar3, Mark D Ludman4, Gili Reznik5, Hagit Baris Feldman5,6, Nadra Nasser Samra7,8, Avital Eilat9, Tamar Peretz10, Lilach Peled Peretz11, Tamar Shapira12, Nurit Magal3, Marina Lifshitc Kalis3, Rinat Yerushalmi13, Chana Vinkler14, Sari Liberman15, Lina Basel-Salmon3,16, Mordechai Shohat12, Ephrat Levy-Lahad15, Eitan Friedman2,16, Lily Bazak3, Yael Goldberg17,18. 1. Breast Cancer Center, Oncology Institute, Chaim Sheba Medical Center, Tel-Hashomer, Israel. 2. Susanne Levy Gertner Oncogenetics Unit,The Danek Gertner Institute of Human Genetics, Chaim Sheba Medical Center, Tel-Hashomer, Israel. 3. Recanati Genetics Institute, Beilinson Hospital, Rabin Medical Center, Petach Tikva, Israel. 4. Medical Genetics Institute, Meir Medical Center, Kfar Sava, Israel. 5. The Genetics Institute, Rambam Health Care Campus, Haifa, Israel. 6. The Ruth and Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel. 7. Genetic Unit, Ziv Medical Center, Tzfat, Israel. 8. Faculty of Medicine, Bar Ilan University, Tzfat, Israel. 9. Center for Clinical Genetics, Hebrew University Hadassah Medical Center, Jerusalem, Israel. 10. Sharett Institute of Oncology, Hebrew University-Hadassah Medical Center, Jerusalem, Israel. 11. The Genetics Institute, The Emek Medical Center, Afula, Israel. 12. Maccabi Health Services, Rehovot, Israel. 13. Davidoff Cancer Center, Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel. 14. Institute of Medical Genetics, Wolfson Medical Center, Holon, Israel. 15. Medical Genetics Institute, Shaare Zedek Medical Center, Jerusalem, Israel. 16. The Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel. 17. Recanati Genetics Institute, Beilinson Hospital, Rabin Medical Center, Petach Tikva, Israel. yaelgo43@gmail.com. 18. Maccabi Health Services, Rehovot, Israel. yaelgo43@gmail.com.
Abstract
PURPOSE: While the spectrum of germline mutations in BRCA1/2 genes in the Israeli Jewish population has been extensively studied, there is a paucity of data pertaining to Israeli Arab high-risk cases. METHODS: Consecutive Israeli Arab breast and/or ovarian cancer patients were recruited using an ethically approved protocol from January 2012 to February 2019. All ovarian cancer cases were referred for BRCA genotyping. Breast cancer patients were offered BRCA sequencing and deletion/duplication analysis after genetic counseling, if the calculated risk for carrying a BRCA mutation by risk prediction algorithms was ≥10%. RESULTS: Overall, 188 patients participated; 150 breast cancer cases (median age at diagnosis: 40 years, range 22-67) and 38 had ovarian cancer (median age at diagnosis: 52.5 years, range 26-79). Of genotyped cases, 18 (10%) carried one of 12 pathogenic or likely-pathogenic variants, 12 in BRCA1, 6 in BRCA2. Only one was a rearrangement. Three variants recurred in more than one case; one was detected in five seemingly unrelated families. The detection rate for all breast cancer cases was 4%, 5% in bilateral breast cancer cases and 3% if breast cancer was diagnosed < 40 years. Of patients with ovarian cancer, 12/38 (32%) were carriers; the detection rate reached 75% (3/4) among patients diagnosed with both breast and ovarian cancer. CONCLUSIONS: The overall yield of comprehensive BRCA1/2 testing in high-risk Israeli Arab individuals is low in breast cancer patients, and much higher in ovarian cancer patients. These results may guide optimal cancer susceptibility testing strategy in the Arab-Israeli population.
PURPOSE: While the spectrum of germline mutations in BRCA1/2 genes in the Israeli Jewish population has been extensively studied, there is a paucity of data pertaining to Israeli Arab high-risk cases. METHODS: Consecutive Israeli Arab breast and/or ovarian cancerpatients were recruited using an ethically approved protocol from January 2012 to February 2019. All ovarian cancer cases were referred for BRCA genotyping. Breast cancerpatients were offered BRCA sequencing and deletion/duplication analysis after genetic counseling, if the calculated risk for carrying a BRCA mutation by risk prediction algorithms was ≥10%. RESULTS: Overall, 188 patients participated; 150 breast cancer cases (median age at diagnosis: 40 years, range 22-67) and 38 had ovarian cancer (median age at diagnosis: 52.5 years, range 26-79). Of genotyped cases, 18 (10%) carried one of 12 pathogenic or likely-pathogenic variants, 12 in BRCA1, 6 in BRCA2. Only one was a rearrangement. Three variants recurred in more than one case; one was detected in five seemingly unrelated families. The detection rate for all breast cancer cases was 4%, 5% in bilateral breast cancer cases and 3% if breast cancer was diagnosed < 40 years. Of patients with ovarian cancer, 12/38 (32%) were carriers; the detection rate reached 75% (3/4) among patients diagnosed with both breast and ovarian cancer. CONCLUSIONS: The overall yield of comprehensive BRCA1/2 testing in high-risk Israeli Arab individuals is low in breast cancerpatients, and much higher in ovarian cancerpatients. These results may guide optimal cancer susceptibility testing strategy in the Arab-Israeli population.
Authors: Roberta Zuntini; Elena Bonora; Laura Maria Pradella; Laura Benedetta Amato; Michele Vidone; Sara De Fanti; Irene Catucci; Laura Cortesi; Veronica Medici; Simona Ferrari; Giuseppe Gasparre; Paolo Peterlongo; Marco Sazzini; Daniela Turchetti Journal: Int J Mol Sci Date: 2021-05-29 Impact factor: 5.923