Fax: (813) 558-4807
BRCA1 and BRCA2 mutations account for a large proportion of ovarian carcinoma cases
Version of Record online: 14 NOV 2005
Copyright © 2005 American Cancer Society
Volume 104, Issue 12, pages 2807–2816, 15 December 2005
How to Cite
Pal, T., Permuth-Wey, J., Betts, J. A., Krischer, J. P., Fiorica, J., Arango, H., LaPolla, J., Hoffman, M., Martino, M. A., Wakeley, K., Wilbanks, G., Nicosia, S., Cantor, A. and Sutphen, R. (2005), BRCA1 and BRCA2 mutations account for a large proportion of ovarian carcinoma cases. Cancer, 104: 2807–2816. doi: 10.1002/cncr.21536
- Issue online: 8 DEC 2005
- Version of Record online: 14 NOV 2005
- Manuscript Accepted: 15 JUL 2005
- Manuscript Revised: 20 JUN 2005
- Manuscript Received: 16 NOV 2004
- Department of Defense. Grant Number: DAMD 17-98-1-8659
- BRCA1 and 2 mutations;
- risk assessment;
- ovarian neoplasms
It is believed that BRCA1 and BRCA2 germline mutations account for the majority of hereditary ovarian carcinomas; however, to the authors' knowledge, there are scant data on the prevalence and spectrum of mutations, genotype/phenotype correlations, tumor histology, and family history characteristics. To address this gap, the authors conducted a population-based study of 232 incident epithelial ovarian carcinomas in the Tampa Bay area.
Genetic testing for the BRCA1 and BRCA2 genes was performed through full sequencing and BRCA1 rearrangement testing.
Of 209 women with invasive ovarian carcinoma, 32 women (15.3%) had mutations in BRCA1 or BRCA2, including 20 BRCA1 mutations and 12 BRCA2 mutations. Of the BRCA2 mutations, 58% were outside the “ovarian cancer cluster region” (OCCR). Variants of uncertain significance were detected in 8.2% of women with invasive ovarian carcinoma. No mutations were identified in women with borderline or invasive mucinous tumors. Among the BRCA mutation-positive women, 63% had serous tumors. A family history of breast and/or ovarian carcinoma was reported in 65%, 75%, and 43.5% of relatives of BRCA1 carriers, BRCA2 carriers, and non-BRCA1/BRCA2 carriers, respectively.
The data from this study suggested that 1) previous studies may have underestimated the frequency of BRCA1 and BRCA2 mutations in ovarian carcinomas, especially outside the OCCR; 2) it may be reasonable to offer genetic counseling to any woman with an invasive, nonmucinous epithelial ovarian tumor; and 3) among patients with invasive ovarian carcinoma, family history is not sufficiently accurate to predict mutation status. Cancer 2005. © 2005 American Cancer Society.