The yield of full BRCA1/2 genotyping in Israeli Arab high-risk breast/ovarian cancer patients
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.
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%.
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.
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.
KeywordsIsraeli Arabs Breast cancer BRCA1 BRCA2 Recurrent mutations Ovarian cancer
This study was not funded by any grant.
Compliance with ethical standards
Conflict of interest
All authors declare no conflict of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study was approved by the IRB in the participating institutions.
As data were aggregative and anonymous no informed consent was required by the institutional IRB.
- 4.The Central Bureau of Statistics. https://www.cbs.gov.il/en/subjects/Pages/Population.aspx. Accessed 16 Mar 2019
- 5.Spencer C. Tucker; Priscilla Roberts (12 May 2008). The Encyclopedia of the Arab-Israeli Conflict: A Political, Social, and Military History [4 volumes]: A Political, Social, and Military History. ABC-CLIO. p. 503. ISBN 978-1-85109-842-2Google Scholar
- 8.CI5 - Home [Internet]. Cancer Incid. Five Cont. Vol X Electron. Version. http://ci5.iarc.fr/Default.aspx. Accessed 15 Oct 2018
- 16.The Penn II Risk Model, BRCA 1 and BRCA 2 Mutation Predictor [Internet]. https://pennmodel2.pmacs.upenn.edu/penn2/index.jsp. Accessed 2 Sep 2017
- 17.BRCA Calculator [Internet]. http://www.myriadpro.com/brca-risk-calculator/calc.html. Accessed 7 Sep 2017.
- 28.Online Research Resources Developed at NHGRI [Internet]. Online Res. Resour. Dev. NHGRI. https://research.nhgri.nih.gov/. Accessed 15 Oct 2018
- 30.Paperna T, Sharon-Shwartzman N, Kurolap A, Goldberg Y, Moustafa N, Carasso Y et al (2019) Homozygosity for CHEK2 p.Gly167Arg leads to a unique cancer syndrome with multiple complex chromosomal translocations in peripheral blood karyotype. J Med Genet. https://doi.org/10.1136/jmedgenet-2018-105824 CrossRefPubMedGoogle Scholar
- 34.Baris HN, Barnes-Kedar I, Toledano H, Halpern M, Hershkovitz D, Lossos A et al (2016) Constitutional mismatch repair deficiency in Israel: high proportion of founder mutations in MMR genes and consanguinity. Pediatr Blood Cancer 63:418–427. https://doi.org/10.1002/pbc.25818 CrossRefPubMedGoogle Scholar