FREQUENCY OF THE BRCA1 185DELAG MUTATION AMONG JEWISH WOMEN WITH OVARIAN-CANCER AND MATCHED POPULATION-CONTROLS

Among women of Ashkenazi Jewish origin, a frameshift mutation of the B RCA1 gene, designated 185delAG, occurs with a carrier frequency of app roximately 1% and is estimated to account for about 39% of ovarian can cer cases occurring prior to age 50 years. To determine the actual fre quency of this mutation among Jewish women with ovarian cancer, we tes ted DNA collected as part of an ongoing population-based case-control study of genetic and environmental factors for epithelial ovarian canc er in eastern Massachusetts. Using single-stranded conformational poly morphism analysis followed by direct sequencing, we found that 6 (19.4 %) of 31 Jewish patients were carriers for a 185delAG mutation compare d to 0 of 23 Jewish controls (P = 0.03). Using empiric logits, the est imated relative risk for ovarian cancer associated with a 185delAG mut ation is 12.0. The average age of the 6 patients with mutations was 48 .3 years, significantly younger than the average of 57.4 years observe d for the 25 patients without the mutation (P = 0.05). For ovarian can cer diagnosed prior to age 50 years, three (37.5%) of eight patients c arried the mutation, None of the six patients with the mutation had a history consistent with hereditary breast ovarian cancer syndrome, alt hough two had a personal history of prior cancer. Our results provide empiric confirmation of the estimated prevalence of 185delAG mutations among Jewish women with ovarian cancer.