Germline BRCA1-2 mutations in non-Ashkenazi families with double primary breast and ovarian cancer

Objective. Ashkenazi women with double primary breast and ovarian cancer ha ve a high prevalence (57%) of germline Jewish founder mutations in the BRCA 1 (185delAG, 5382insC) and BRCA2 (6174delT) genes. The purpose of this stud y was to determine the frequency and type of BRCA1-2 mutations in no Ashken azi families with at least one member having double primary breast and ovar ian cancer. Methods. Women at increased risk for cancer based upon their family history were enrolled at the University of Texas Southwestern Familial Cancer Regi stry between 1992 and 2000. Blood samples from patients desiring genetic te sting were sent for complete DNA sequencing of the BRCA1 and BRCA2 genes. F amilies with a member having both breast and ovarian cancer were identified and clinical data were obtained. Results. Sixty-two (7%) of 900 enrolled families were non-Ashkenazi and had at least one member with double primary breast and ovarian cancer. Twenty- one families bad members who underwent genetic testing; 41 did not. Thirtee n (62%) families had a germline BRCA1 (n = 11) or BRCA2 (n = 2) mutation; o nly one Jewish founder mutation (185delAG) was detected. Eight (38%) famili es tested negative. Six (86%) of seven women undergoing genetic testing who themselves had double primary breast and ovarian cancer were BRCA1-2 mutat ion carriers. Conclusions. Germline BRCA1-2 mutations are common in non-Ashkenazi familie s with a member having double primary breast and ovarian cancer. These muta tions occurred throughout both genes, emphasizing the need for comprehensiv e sequencing. One family had the BRCA2 6985delCT mutation, which lies beyon d the " ovarian cancer cluster " region. (C) 2001 Academic Press.