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Hereditary breast cancer in Jews

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Abstract

A family history of breast cancer poses higher risks for Jewish versus non-Jewish women, particularly for early-onset breast cancer. This appears to be due in large part to the high prevalence (2.5%) of three BRCA1 and BRCA2 founder mutations in Ashkenazi Jews. About 4 to 8% of non-Jewish male breast cancer cases versus 19% of Jewish male breast cancer cases carry germline BRCA mutations. Jewish women are disproportionately impacted by BRCA mutations throughout life, with a 10% carrier rate for breast cancer diagnosed at any age and a 21 to 30% carrier rate for breast cancer diagnosed by age 40. Comparable rates in non-Jewish populations are 6.1% for breast cancer diagnosed before age 50. Lifetime penetrance estimates based on genotyping of probands have ranged widely in Jewish and non-Jewish populations. However, a study of 1008 Jewish women with breast cancer which extended genotyping to relatives found high penetrance rates with considerably smaller standard errors. This study and studies of early-onset incident breast cancer in non-Jews have found that at least half of high-risk cases would be missed by family history screening alone. While the carrier rate in non-Jewish populations is too low to consider genetic screening, the carrier rate in Ashkenazi Jews is high and genetic screening poses fewer technical barriers. The high genetic attributable cancer risks of Ashkenazi BRCA founder mutations, the sobering lethality of ovarian and early onset breast cancers, and the increasing clarity about effectiveness of medical interventions make imperative further dialogue and research to keep guidelines for genetic screening up to date.

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Rubinstein, W.S. Hereditary breast cancer in Jews. Familial Cancer 3, 249–257 (2004). https://doi.org/10.1007/s10689-004-9550-2

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