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Last month’s JAMA Onc investigation shows more genetic woes for Ashkenazi Jews. An Ashkenazi heritage has long been married to a notorious list of endogamous pathologies which is fast fodder for Step 1 examinations. But what can we do for these real-world patients in the molecular era? The New York Breast Cancer Study prospectively performed genomic analyses of Ashkenazi Jewish women diagnosed with invasive breast cancers from 1996-2000, regardless of family history or age. As reported in 2003, a shocking 10% of these >1K patients harbored one of the three (then) known “ancient founder” mutations in BRCA1/2. This new report used novel genetic testing to find that a further 0.8% of these women carried different BRCA1/2 mutations and another 3.4% carried altogether disparate pathogenic mutations. Why does this matter? Approximately 4 in 5 Jews worldwide share an Ashkenazi heritage...and an increased risk for early breast and ovarian cancer regardless of immediate family history. So we just gave you further reason to send your Bubbe with breast cancer for a full genetic panel. Oy.