Prevalence Rates of Pathogenic Mutations in the BRCA1 and BRCA2 Genes in Families with Different Disease Histories: Results from the German Consortium for Hereditary Breast and Ovarian Cancer

* From 1997-2009 more than 6,000 families were screened for pathogenic mutations in BRCA1/2.


* Mutation analysis was performed by DHPLC (denaturing high-performance liquid chromatography) pre-screening, direct sequencing of suspect fragments and MLPA (multiplex ligation-dependant probe amplification) in at least one index case of these families.

* Complete pedigree information over three generations was used for the analysis.

* The highest mutation prevalence rate (78%) was seen in families with at least two relatives affected by pre-menopausal breast cancer and at least two affected by ovarian cancer at any age.

* Importantly, the presence of a single woman affected by breast and ovarian cancer or bilateral breast cancer with first breast cancer under the age of 41 was associated with a BRCA1/2 mutation prevalence of 53% (59%) and 34%) respectively.

* Interestingly, low mutation prevalence rates of <10%> with only one case of male breast cancer (9%), and in families with three or more cases of postmenopausal breast cancer (7%), the former being only BRCA2 mutations.