BRCA1 and BRCA2 mutations account for a large proportion of ovarian carcinoma cases

• Published in: Cancer Vol. 104; no. 12; pp. 2807 - 2816
• Main Authors: Pal, Tuya, Permuth‐Wey, Jenny, Betts, Judith A., Krischer, Jeffrey P., Fiorica, James, Arango, Hector, LaPolla, James, Hoffman, Mitchell, Martino, Martin A., Wakeley, Katie, Wilbanks, George, Nicosia, Santo, Cantor, Alan, Sutphen, Rebecca
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 15-12-2005; Wiley-Liss
• Subjects: Adult; Age Distribution; Aged; Biological and medical sciences; BRCA1 and 2 mutations; Cohort Studies; Confidence Intervals; familial; Female; Female genital diseases; Gene Expression Regulation, Neoplastic; Genes, BRCA1; Genes, BRCA2; Genetic Counseling; Genetic Predisposition to Disease - epidemiology; Genetic Testing; genetics; Gynecology. Andrology. Obstetrics; Humans; Incidence; Medical sciences; Middle Aged; Mutation; Neoplasm Invasiveness - pathology; ovarian neoplasms; Ovarian Neoplasms - epidemiology; Ovarian Neoplasms - genetics; Ovarian Neoplasms - pathology; Pedigree; pouplation‐based; Probability; Prognosis; Risk Assessment; Survival Rate; Tumors; risk assessment; Ovary carcinoma; pouplation-based; Malignant tumor; Epidemiology; Female genital diseases; Ovarian diseases; familial; ovarian neoplasms; Cancerology; BRCA2 gene; Proportion; Risk factor; Genetics; Mutation; BRCA1 and 2 mutations; BRCA1 gene; Tumor suppressor gene
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.21536

BACKGROUND
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.
METHODS
Genetic testing for the BRCA1 and BRCA2 genes was performed through full sequencing and BRCA1 rearrangement testing.
RESULTS
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.
CONCLUSIONS
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.
In this population‐based study of incident epithelial ovarian carcinomas, the authors demonstrated that the frequency of BRCA1 and BRCA2 mutations among women with ovarian carcinoma was higher than reported previously. The current data suggested that it may be reasonable to offer genetic counseling to any woman with invasive epithelial ovarian carcinoma, because family history is not sufficiently accurate to predict the presence or absence of a mutation.