Variation of breast cancer risk among BRCA1/2 carriers Journal Article


Authors: Begg, C. B.; Haile, R. W.; Borg, A.; Malone, K. E.; Concannon, P.; Thomas, D. C.; Langholz, B.; Bernstein, L.; Olsen, J. H.; Lynch, C. F.; Anton-Culver, H.; Capanu, M.; Liang, X.; Hummer, A. J.; Sima, C.; Bernstein, J. L.
Article Title: Variation of breast cancer risk among BRCA1/2 carriers
Abstract: Context: The risk of breast cancer in BRCA1 and BRCA2 mutation carriers has been examined in many studies, but relatively little attention has been paid to the degree to which the risk may vary among carriers. Objectives: To determine the extent to which risks for BRCA1 and BRCA2 carriers vary with respect to observable and unobservable characteristics. Design, Setting, and Participants: Probands were identified from a population-based, case-control study (Women's Environmental Cancer and Radiation Epidemiology [WECARE]) of asynchronous contralateral breast cancer conducted during the period of January 2000 to July 2004. Participants previously diagnosed with contralateral breast cancer or unilateral breast cancer were genotyped for mutations in BRCA1 and BRCA2. All participants had their initial breast cancer diagnosed during the period of January 1985 to December 2000, before the age of 55 years. Main Outcome Measure: Incidence of breast cancer in first-degree female relatives of the probands was examined and compared on the basis of proband characteristics and on the basis of variation between families. Results: Among the 1394 participants with unilateral breast cancer, 73 (5.2%) were identified as carriers of deleterious mutations (42 with BRCA1 and 31 with BRCA2). Among the 704 participants with contralateral breast cancer, 108 (15.3%) were identified as carriers of deleterious mutations (67 with BRCA1 and 41 with BRCA2). Among relatives of carriers, risk was significantly associated with younger age at diagnosis in the proband (P=.04), and there was a trend toward higher risk for relatives of contralateral breast cancer vs unilateral breast cancer participants (odds ratio, 1.4 [95% confidence interval, 0.8-2.4]; P=.28). In addition, there were significant differences in risk between carrier families after adjusting for these observed characteristics. Conclusion: There exists broad variation in breast cancer risk among carriers of BRCA1 and BRCA2 mutations. ©2008 American Medical Association. All rights reserved.
Keywords: adult; controlled study; aged; middle aged; gene mutation; major clinical study; genetics; mutation; cancer risk; cancer incidence; breast cancer; incidence; genetic variability; breast neoplasms; brca1 protein; brca2 protein; heterozygote; risk; tumor suppressor gene; statistical analysis; genes, brca1; genes, brca2; nucleotide sequence; breast tumor; dna mutational analysis; matched-pair analysis
Journal Title: JAMA - Journal of the American Medical Association
Volume: 299
Issue: 2
ISSN: 0098-7484
Publisher: American Medical Association  
Date Published: 2008-01-09
Start Page: 194
End Page: 201
Language: English
DOI: 10.1001/jama.2007.55-a
PUBMED: 18182601
PROVIDER: scopus
PMCID: PMC2714486
DOI/URL:
Notes: --- - "Cited By (since 1996): 65" - "Export Date: 17 November 2011" - "CODEN: JAMAA" - "Molecular Sequence Numbers: GENBANK: NM_000059, U14680" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Amanda J Hummer
    60 Hummer
  2. Camelia S Sima
    204 Sima
  3. Colin B Begg
    239 Begg
  4. Marinela Capanu
    211 Capanu
  5. Jonine L Bernstein
    104 Bernstein
  6. Xiaolin Liang
    41 Liang