THE FOUNDER MUTATIONS 185DELAG AND 5382INSC IN BRCA1 AND 6174DELT IN BRCA2 APPEAR IN 60-PERCENT OF OVARIAN-CANCER AND 30-PERCENT OF EARLY-ONSET BREAST-CANCER PATIENTS AMONG ASHKENAZI WOMEN

The mutations 185delAG, 188del11, and 5382insC in the BRCA1 gene and G 174delT in the BRCA2 gene were analyzed in 199 Ashkenazi and 44 non-As hkenazi Jewish unrelated patients with breast and/or ovarian cancer. O f the Jewish Ashkenazi women with ovarian cancer, 62% (13/21) had one of the target mutations, as did 30% (13/43) of women with breast cance r alone diagnosed before the age 40 years and 10% (15/141) of those wi th breast cancer diagnosed after the age 40 years. Age at ovarian canc er diagnosis was not associated with carrier status. Of 99 Ashkenazi p atients with no family history of breast and/or ovarian cancer, 10% ca rried one of the mutations; in two of them the mutation was proved to be paternally transmitted. One non-Ashkenazi Jewish ovarian cancer pat ient from Iraq carried the 185delAG mutation. Individual mutation freq uencies among breast cancer Ashkenazi patients were 6.7% for 185delAG, 2.2% for 5382insC, and 4.5% for 6174delT, among ovarian cancer patien ts; 185delAG and G174delT were about equally common (33% and 29%, resp ectively), but no ovarian cancer patient carried the 5382insC. More mu tations responsible for inherited breast and ovarian cancer probably r emain to be found in this population, since 79% of high-incidence brea st cancer families and 35% of high-incidence breast/ovarian cancer fam ilies had none of the three known founder mutations.