HIGH-FREQUENCY OF BRCA1 AND BRCA2 GERMLINE MUTATIONS IN ASHKENAZI JEWISH OVARIAN-CANCER PATIENTS, REGARDLESS OF FAMILY HISTORY

To better understand the role of germline BRCA mutations in ovarian ca ncer in Ashkenazi Jews, we tested 29 consecutive patients admitted to our service for the three mutations common in this ethnic group. These mutations are 185delAG and 5382insC in BRCA1 and 6174delT in BRCA2. S ix patients had both breast and ovarian cancer, and 23 had ovarian can cer only. In the first group, all women had germline mutations, 2 with each mutation. Of 23 ovarian cancer patients, 11 were carriers (48%): 6 of 185delAG, 2 of 5382insC, and 3 of 6174delT. Regarding family his tory, of 13 women with no family history, 3 (23%) were carriers. Of 10 women with any family history of breast or ovarian cancer, 8 (80%) we re carriers. We discuss possible explanations for this surprisingly hi gh carrier rate, including a high proportion of familial disease coupl ed with lack of adequate family history, lower penetrance than previou sly expected, or increasing penetrance in recent generations due to no ngenetic factors. Our data suggest that genetic testing is merited in all Ashkenazi women with ovarian cancer, regardless of family history. (C) 1997 Academic Press.