Hereditary breast/ovarian cancer – pitfalls in genetic counseling

Authors

  • E Dagan,

    1. Institute of Human Genetics, Rambam Medical Center,
    2. Faculty of Welfare and Social Sciences, Division of Nursing, Haifa University,
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  • R Gershoni-Baruch

    1. Institute of Human Genetics, Rambam Medical Center,
    2. Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
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Corresponding author: Dr R Gershoni-Baruch, Institute of Human Genetics, Rambam Medical Center, Haifa, Israel. Tel.: +972 48542456/604; fax: +972 48543029; e-mail: rgershoni@rambam.health.gov.il

Abstract

Genetic counseling and risk assessment, given to women with a family history of breast/ovarian cancer, are regularly based on pedigree analysis. In the Ashkenazi Jewish population, hereditary breast/ovarian cancer is mainly attributed to three founder mutations, namely, 185delAG, 5382insC, and 6174delT, in BRCA1/2 genes. The overall frequency of these mutations, in the Jewish Ashkenazi population, is as high as 2.5%. Based on clinical and family history data, the results of BRCA molecular testing, in Ashkenazi individuals at risk, are appropriately anticipated in most cases. Here we report on five families, in which the segregation of BRCA1/2 mutations, in affected and unaffected family members, was unexpected, emphasizing the need to test, for founder mutations, every Ashkenazi individual at risk, irrespective of the genotype of affected family members. Ultimately, risk assessments and recommendations, in Ashkenazi women, should be invariably based on the results of genetic testing.

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