BRCA1 and BRCA2 mutations account for a large proportion of ovarian carcinoma cases.
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.
Pal
Tuya
T
Division of Cancer Prevention and Control, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33617, USA.
Permuth-Wey
Jenny
J
Betts
Judith A
JA
Krischer
Jeffrey P
JP
Fiorica
James
J
Arango
Hector
H
LaPolla
James
J
Hoffman
Mitchell
M
Martino
Martin A
MA
Wakeley
Katie
K
Wilbanks
George
G
Nicosia
Santo
S
Cantor
Alan
A
Sutphen
Rebecca
R
D000328:Adult; D017677:Age Distribution; D000368:Aged; D015331:Cohort Studies; D016001:Confidence Intervals; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D005817:Genetic Counseling; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D005820:Genetic Testing; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D009154:Mutation; D009361:Neoplasm Invasiveness / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D011336:Probability; D011379:Prognosis; D018570:Risk Assessment; D015996:Survival Rate