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

Authors

  • Tuya Pal M.D.,

    1. Division of Cancer Prevention and Control, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida
    2. Department of Interdisciplinary Oncology, College of Medicine, The University of South Florida, Tampa, Florida
    3. The University of South Florida, College of Medicine, Department of Pediatrics at All Children's Hospital, St. Petersburg, Florida
    Search for more papers by this author
  • Jenny Permuth-Wey M.S.,

    Corresponding author
    1. Division of Cancer Prevention and Control, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida
    2. Department of Interdisciplinary Oncology, College of Medicine, The University of South Florida, Tampa, Florida
    • Certified Genetic Counselor, Lifetime Cancer Screening and Prevention Center at the H. Lee Moffitt Cancer Center and Research Institute, 4117 East Fowler Avenue, Tampa, FL 33617===

    Search for more papers by this author
    • Fax: (813) 558-4807

  • Judith A. Betts R.N.,

    1. Division of Cancer Prevention and Control, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida
    Search for more papers by this author
  • Jeffrey P. Krischer Ph.D.,

    1. Division of Cancer Prevention and Control, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida
    2. The University of South Florida, College of Medicine, Department of Pediatrics at All Children's Hospital, St. Petersburg, Florida
    Search for more papers by this author
  • James Fiorica M.D.,

    1. Division of Cancer Prevention and Control, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida
    2. Department of Interdisciplinary Oncology, College of Medicine, The University of South Florida, Tampa, Florida
    3. Department of Gynecologic Oncology, College of Medicine, The University of South Florida, Tampa, Florida
    Search for more papers by this author
  • Hector Arango M.D.,

    1. Department of Gynecologic Oncology, Morton Plant Hospital, Clearwater, Florida
    Search for more papers by this author
  • James LaPolla M.D.,

    1. Department of Gynecologic Oncology, Bayfront Medical Center, St. Petersburg, Florida
    Search for more papers by this author
  • Mitchell Hoffman M.D.,

    1. Department of Obstetrics and Gynecology, College of Medicine, The University of South Florida, Tampa, Florida
    Search for more papers by this author
  • Martin A. Martino M.D.,

    1. Department of Obstetrics and Gynecology, College of Medicine, The University of South Florida, Tampa, Florida
    Search for more papers by this author
  • Katie Wakeley M.D.,

    1. Department of Obstetrics and Gynecology, College of Medicine, The University of South Florida, Tampa, Florida
    Search for more papers by this author
  • George Wilbanks M.D.,

    1. Division of Cancer Prevention and Control, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida
    2. Department of Gynecologic Oncology, College of Medicine, The University of South Florida, Tampa, Florida
    Search for more papers by this author
  • Santo Nicosia M.D.,

    1. Division of Cancer Prevention and Control, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida
    2. Department of Pathology, College of Medicine, The University of South Florida, Tampa, Florida
    Search for more papers by this author
  • Alan Cantor Ph.D.,

    1. Division of Cancer Prevention and Control, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida
    2. Department of Interdisciplinary Oncology, College of Medicine, The University of South Florida, Tampa, Florida
    Search for more papers by this author
  • Rebecca Sutphen M.D.

    1. Division of Cancer Prevention and Control, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida
    2. Department of Interdisciplinary Oncology, College of Medicine, The University of South Florida, Tampa, Florida
    3. The University of South Florida, College of Medicine, Department of Pediatrics at All Children's Hospital, St. Petersburg, Florida
    Search for more papers by this author

Abstract

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.

Ancillary