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Characterization of BRCA1 and BRCA2 mutations in a large United States sample.

Publication ,  Journal Article
Chen, S; Iversen, ES; Friebel, T; Finkelstein, D; Weber, BL; Eisen, A; Peterson, LE; Schildkraut, JM; Isaacs, C; Peshkin, BN; Corio, C ...
Published in: J Clin Oncol
February 20, 2006

PURPOSE: An accurate evaluation of the penetrance of BRCA1 and BRCA2 mutations is essential to the identification and clinical management of families at high risk of breast and ovarian cancer. Existing studies have focused on Ashkenazi Jews (AJ) or on families from outside the United States. In this article, we consider the US population using the largest US-based cohort to date of both AJ and non-AJ families. METHODS: We collected 676 AJ families and 1,272 families of other ethnicities through the Cancer Genetics Network. Two hundred eighty-two AJ families were population based, whereas the remainder was collected through counseling clinics. We used a retrospective likelihood approach to correct for bias induced by oversampling of participants with a positive family history. Our approach takes full advantage of detailed family history information and the Mendelian transmission of mutated alleles in the family. RESULTS: In the US population, the estimated cumulative breast cancer risk at age 70 years was 0.46 (95% CI, 0.39 to 0.54) in BRCA1 carriers and 0.43 (95% CI, 0.36 to 0.51) in BRCA2 carriers, whereas ovarian cancer risk was 0.39 (95% CI, 0.30 to 0.50) in BRCA1 carriers and 0.22 (95% CI, 0.14 to 0.32) in BRCA2 carriers. We also reported the prospective risks of developing cancer for cancer-free carriers in 10-year age intervals. We noted a rapid decrease in the relative risk of breast cancer with age and derived its implication for genetic counseling. CONCLUSION: The penetrance of BRCA mutations in the United States is largely consistent with previous studies on Western populations given the large CIs on existing estimates. However, the absolute cumulative risks are on the lower end of the spectrum.

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Published In

J Clin Oncol

DOI

EISSN

1527-7755

Publication Date

February 20, 2006

Volume

24

Issue

6

Start / End Page

863 / 871

Location

United States

Related Subject Headings

  • United States
  • Risk Assessment
  • Retrospective Studies
  • Penetrance
  • Ovarian Neoplasms
  • Oncology & Carcinogenesis
  • Mutation
  • Middle Aged
  • Jews
  • Incidence
 

Citation

APA
Chicago
ICMJE
MLA
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Chen, S., Iversen, E. S., Friebel, T., Finkelstein, D., Weber, B. L., Eisen, A., … Parmigiani, G. (2006). Characterization of BRCA1 and BRCA2 mutations in a large United States sample. J Clin Oncol, 24(6), 863–871. https://doi.org/10.1200/JCO.2005.03.6772
Chen, Sining, Edwin S. Iversen, Tara Friebel, Dianne Finkelstein, Barbara L. Weber, Andrea Eisen, Leif E. Peterson, et al. “Characterization of BRCA1 and BRCA2 mutations in a large United States sample.J Clin Oncol 24, no. 6 (February 20, 2006): 863–71. https://doi.org/10.1200/JCO.2005.03.6772.
Chen S, Iversen ES, Friebel T, Finkelstein D, Weber BL, Eisen A, et al. Characterization of BRCA1 and BRCA2 mutations in a large United States sample. J Clin Oncol. 2006 Feb 20;24(6):863–71.
Chen, Sining, et al. “Characterization of BRCA1 and BRCA2 mutations in a large United States sample.J Clin Oncol, vol. 24, no. 6, Feb. 2006, pp. 863–71. Pubmed, doi:10.1200/JCO.2005.03.6772.
Chen S, Iversen ES, Friebel T, Finkelstein D, Weber BL, Eisen A, Peterson LE, Schildkraut JM, Isaacs C, Peshkin BN, Corio C, Leondaridis L, Tomlinson G, Dutson D, Kerber R, Amos CI, Strong LC, Berry DA, Euhus DM, Parmigiani G. Characterization of BRCA1 and BRCA2 mutations in a large United States sample. J Clin Oncol. 2006 Feb 20;24(6):863–871.

Published In

J Clin Oncol

DOI

EISSN

1527-7755

Publication Date

February 20, 2006

Volume

24

Issue

6

Start / End Page

863 / 871

Location

United States

Related Subject Headings

  • United States
  • Risk Assessment
  • Retrospective Studies
  • Penetrance
  • Ovarian Neoplasms
  • Oncology & Carcinogenesis
  • Mutation
  • Middle Aged
  • Jews
  • Incidence