The aim of the present study is to analyze the relationship of the incidence of 
mutations in the two major genes BRCA1 and BRCA2 conferring risk of breast 
cancer (BC) and ovarian cancer (OC) with the cancer burden in families and with 
the presence and age of onset of BC/OC. We included 704 index patients (IP) and 
668 family members of the IP who tested positive for BRCA1/BRCA2 who were 
studied in the Program of Genetic Counselling in Cancer of the Valencia 
Community (Spain). We found 129 IPs with deleterious mutations (18.3%), 59 in 
BRCA1 and 70 in BRCA2, detecting 396 mutations in this kindred. The incidence of 
mutations and their distribution between BRCA1 and BRCA2 showed a significantly 
uneven incidence among the family groups (P < 0.001). We found 179 tumors in the 
396 mutation carriers (45%) and detected only 11 cancers among the 272 
non-mutation carriers (P < 0.001). No differences in the tumor prevalence or the 
age of onset of cancer between the genes among the mutation carriers were found. 
The mutation carriers showed a 50% probability of having BC/OC at a median age 
of 49 years (95% CI 46-52 years) and 78% at the age of 70 years (95% CI: 
71-85%). In conclusion the family burden of BC and OC is strongly associated 
with the incidence of BRCAs mutations and could foretell which of the two BRCAs 
genes is more likely to have mutations. Mutation carriers have a 50% risk of 
having BC/OC by the age of 50 years.