Carrier screening program for BRCA1/BRCA2 pathogenic variants among Ashkenazi Jewish women in Israel: An observational study

Abstract

PurposeThe aim of the study was to evaluate the results of a large-scale BRCA1/2 carrier screening program among Ashkenazi Jewish (AJ) women. MethodsWe performed a cross-sectional study of women who were eligible for BRCA1/2 screening program. Women who self-reported as complete or partial AJ were screened for 14 pathogenic variants in BRCA1/2 genes, following the Israeli Ministry of Health’s national screening program. ResultsThe study included 13,502 women who underwent screening between June 2020 and June 2022. The prevalence of the pathogenic variants in BRCA1/2 was 0.89% (120 of 13,502) among the tested women. Of the 14 variants tested, only 6 variants were detected. Three variants, known as the founder variants among AJ, accounted for 96.6% of identified variants (NM_000059.4(BRCA2):c.5946del, p.(Ser1982fs); NM_007294.4(BRCA1):c.68_69del, p.(Glu23fs); NM_007294.4(BRCA1):c.5266dup, p.(Gln1756fs)). The tested women were younger and of a higher socioeconomic status compared with the eligible non-tested women. ConclusionThe study provides a new insight into a large carrier screening program for BRCA1/2 pathogenic variants in AJ women in Israel. These findings present real-world prevalence of women who are heterozygous for BRCA1/2 pathogenic variants in AJ population and the importance of such programs.