Abstract
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.
Highlights
Pathogenic variants in the BRCA1 and BRCA2 genes are linked to an increased risk for female breast and ovarian cancer, male breast cancer, prostate cancer, pancreatic cancer, and certain other cancers[1]
We sought to characterize a cohort of individuals who carry one or more of the three Ashkenazi Jewish founder variants as related to 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
We identified 2,853 individuals who carry one or more of the three Ashkenazi Jewish BRCA1/2 founder variants (Table 1)
Summary
Pathogenic variants in the BRCA1 and BRCA2 genes are linked to an increased risk for female breast and ovarian cancer (including early-onset breast cancer), male breast cancer, prostate cancer, pancreatic cancer, and certain other cancers[1]. We sought to characterize a cohort of individuals who carry one or more of the three Ashkenazi Jewish founder variants as related to 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. We focused on these two characteristics because they can enable individuals to learn their BRCA status before developing cancer, providing opportunities for cancer prevention and/or early detection. Last fully Ashkenazi Jewish ancestor Self 1 parent or 2–3 grandparents 1 grandparent 1 grandparent or great-grandparent 1 great-grandparent More distant than great-grandparent No detectable Ashkenazi Jewish ancestry
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