Identifying Ashkenazi Jewish BRCA1/2 founder variants in individuals who do not self-report Jewish ancestry

• Published in: Scientific reports Vol. 10; no. 1; p. 7669
• Main Authors: Tennen, Ruth I., Laskey, Sarah B., Koelsch, Bertram L., McIntyre, Matthew H., Tung, Joyce Y.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 06-05-2020; Nature Publishing Group
• Subjects: 45; 631/208/2489/1512; 631/208/2489/68; 631/67/2195; 692/699/67/2195; 692/699/67/68; Adolescent; Adult; Aged; Aged, 80 and over; BRCA1 protein; BRCA1 Protein - genetics; BRCA2 protein; BRCA2 Protein - genetics; Breast cancer; Cancer; Family medical history; Female; Founder Effect; Genealogy; Genetic Association Studies; Genetic Predisposition to Disease; Genetic screening; Genetic Testing; Genetic Variation; Genetics; Health risk assessment; Hereditary Breast and Ovarian Cancer Syndrome - epidemiology; Hereditary Breast and Ovarian Cancer Syndrome - genetics; Hereditary Breast and Ovarian Cancer Syndrome - prevention & control; Humanities and Social Sciences; Humans; Jews - genetics; Male; Middle Aged; multidisciplinary; Ovarian cancer; Pancreatic cancer; Prostate cancer; Science; Science (multidisciplinary); Self Report; Young Adult
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-63466-x

Current guidelines recommend
BRCA1
and
BRCA2
genetic testing for individuals with a personal or family history of certain cancers. Three
BRCA1/2
founder variants — 185delAG (c.68_69delAG), 5382insC (c.5266dupC), and 6174delT (c.5946delT) — are common in the Ashkenazi Jewish population. We characterized a cohort of more than 2,800 research participants in the 23andMe database who carry one or more of the three Ashkenazi Jewish founder variants, evaluating two characteristics that are typically used to recommend individuals for
BRCA
testing: self-reported Jewish ancestry and family history of breast, ovarian, prostate, or pancreatic cancer. Of the 1,967 carriers who provided self-reported ancestry information, 21% did not self-report Jewish ancestry; of these individuals, more than half (62%) do have detectable Ashkenazi Jewish genetic ancestry. In addition, of the 343 carriers who provided both ancestry and family history information, 44% did not have a first-degree family history of a
BRCA
-related cancer and, in the absence of a personal history of cancer, would therefore be unlikely to qualify for clinical genetic testing. These findings may help inform the discussion around broader access to
BRCA
genetic testing.