Founder BRCA 1 and 2 mutations among a consecutive series of Ashkenazi Jewish ovarian cancer patients

Objective. The purpose of this study was to describe the incidence of the t hree Ashkenazi Jewish founder genetic BRCA 1 and 2 mutations among an unsel ected, consecutive group of Ashkenazi Jewish ovarian cancer patients. Materials and methods. From 7/30/96 to 4/12/99, 92 Ashkenazi Jewish patient s with histologically confirmed epithelial ovarian cancer had surgery. All of these patients had DNA extracted from 5-mu m sections of their paraffin- embedded surgical specimen tissue blocks using the Qiagen QIAamp tissue ext raction kit. A multiplex (triplex) polymerase chain reaction was performed to amplify fragments for the 185delAG, 5382insC, and 6174delT mutations. Th e products were hybridized with normal and mutant probes for each of the th ree mutations. All clinical data were collected retrospectively and statist ical significance was evaluated using the chi(2) test or a two-tailed Fishe r's exact test, depending on the sample size. Results. There were 23 patients positive for one of the three founder BRCA mutations. Fourteen patients were positive for the 185delAG mutation, 2 pat ients were positive for the 5382insC mutation, and 7 patients were positive for the 6174 delT mutation (61, 9, and 30%, respectively). This represente d a 25% incidence (95% CI: 16-34%) of one of the three founder BRCA mutatio ns among our 92 Ashkenazi Jewish ovarian cancer patients. None of the patie nts was positive for more than one mutation. There was no statistically sig nificant difference in parity, histology, grade, or stage between the BRCA founder mutation positive and negative patients. The difference between the percentage of mutation carriers among patients with one affected first-deg ree relative (13/22 or 59%) compared to those without at least one affected first-degree relative (10/70 or 14%) was highly significant (P = 0.001). Conclusions. Ashkenazi Jewish ovarian cancer patients represent a group wit h a high likelihood of being carriers of BRCA 1 and 2 genetic mutations, re gardless of family history. As a result, all ovarian cancer patients who ar e of Ashkenazi Jewish descent should be counseled regarding BRCA 1 and 2 ge netic screening, as well as the potential implications of these results for the patient as well as her relatives in terms of prognosis, screening, che moprevention, and consideration of prophylactic surgical procedures. (C) 20 00 Academic Press.