OBJECTIVE: Evaluation whether Jewish founder mutations in BRCA predispose to borderline tumors as they do to early invasive ovarian cancers. METHODS: All Jewish women with borderline or invasive ovarian tumors, diagnosed over a 5-year period (1994-1999), were identified in the frame of a nationwide epidemiological study on ovarian cancer in Israel. Out of a total of 1489 patients, 1269 were interviewed; of them 256 (20.2%) patients were identified with stage I and II invasive epithelial ovarian tumors, and 233 (18.3%) patients were identified with borderline tumors. All patients underwent interviews, and blood or tissue samples from 117 borderline tumors and 161 early stage invasive tumors were analyzed for the presence of the 185delAG and 5382insC BRCA1, and the 6174delT BRCA2 Jewish founder mutations. RESULTS: Patients with borderline tumors were younger at diagnosis, and more frequently of the serous type (P < 0.001) as compared to patients with early stage ovarian cancer. Prevalence of Jewish founder mutations in BRCA1 and BRCA2 was only 4.3% of patients with borderline tumors as compared to 24.2% of patients with early stage ovarian cancer (P = 0.001). CONCLUSIONS: This nationwide study comparing patients with early stage borderline and invasive epithelial tumors of the ovary confirms our previous pilot study that showed a lower incidence of BRCA mutations in patients with borderline tumors. Our results suggest that the genetic predisposition and the molecular mechanisms underlying tumor initiation differ between invasive and borderline tumors of the ovary.
OBJECTIVE: Evaluation whether Jewish founder mutations in BRCA predispose to borderline tumors as they do to early invasive ovarian cancers. METHODS: All Jewish women with borderline or invasive ovarian tumors, diagnosed over a 5-year period (1994-1999), were identified in the frame of a nationwide epidemiological study on ovarian cancer in Israel. Out of a total of 1489 patients, 1269 were interviewed; of them 256 (20.2%) patients were identified with stage I and II invasive epithelial ovarian tumors, and 233 (18.3%) patients were identified with borderline tumors. All patients underwent interviews, and blood or tissue samples from 117 borderline tumors and 161 early stage invasive tumors were analyzed for the presence of the 185delAG and 5382insCBRCA1, and the 6174delTBRCA2 Jewish founder mutations. RESULTS:Patients with borderline tumors were younger at diagnosis, and more frequently of the serous type (P < 0.001) as compared to patients with early stage ovarian cancer. Prevalence of Jewish founder mutations in BRCA1 and BRCA2 was only 4.3% of patients with borderline tumors as compared to 24.2% of patients with early stage ovarian cancer (P = 0.001). CONCLUSIONS: This nationwide study comparing patients with early stage borderline and invasive epithelial tumors of the ovary confirms our previous pilot study that showed a lower incidence of BRCA mutations in patients with borderline tumors. Our results suggest that the genetic predisposition and the molecular mechanisms underlying tumor initiation differ between invasive and borderline tumors of the ovary.
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