Hereditary breast/ovarian cancer - pitfalls in genetic counseling

Genetic counseling and risk assessment, given to women with a family histor y of breast/ovarian cancer, are regularly based on pedigree analysis. In th e Ashkenazi Jewish population, hereditary breast/ovarian cancer is mainly a ttributed to three founder mutations, namely, 185delAG, 5382insC, and 6174d elT, in BRCA1/2 genes. The overall frequency of these mutations, in the Jew ish Ashkenazi population, is as high as 2.5%. Based on clinical and family history data, the results of BRCA molecular testing, in Ashkenazi individua ls at risk, are appropriately anticipated in most cases. Here we report on five families, in which the segregation of BRCA1/2 mutations, in affected a nd 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 resu lts of genetic testing.