Skip to main content

Advertisement

SpringerLink
Log in

BRCA1 and BRCA2 mutation carriers in the Breast Cancer Family Registry: an open resource for collaborative research

  • Epidemiology
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

The Breast Cancer Family Registry is a resource for interdisciplinary and translational studies of the genetic epidemiology of breast cancer. This resource is available to researchers worldwide for collaborative studies. Herein, we report the results of testing for germline mutations in BRCA1 and BRCA2. We have tested 4,531 probands for mutations in BRCA1 and 4,084 in BRCA2. Deleterious mutations in BRCA1 and BRCA2 were identified for 9.8% of probands tested [233/4,531 (5.1%) for BRCA1 and 193/4,084 (4.7%) for BRCA2]. Of 1,385 Ashkenazi Jewish women tested for only the three founder mutations, 17.4% carried a deleterious mutation. In total, from the proband and subsequent family testing, 1,360 female mutation carriers (788 in BRCA1, 566 in BRCA2, 6 in both BRCA1 and BRCA2) have been identified. The value of the resource has been greatly enhanced by determining the germline BRCA1 and BRCA2 mutation statuses of nearly 6,000 probands.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. John EM, Hopper JL, Beck JC et al (2004) The Breast Cancer Family Registry: an infrastructure for cooperative multinational, interdisciplinary and translational studies of the genetic epidemiology of breast cancer. Breast Cancer Res 6:R375–R389. doi:10.1186/bcr801

    Article  PubMed  Google Scholar 

  2. Apicella C, Peacock SJ, Andrews L et al (2006) Determinants of preferences for genetic counselling in Jewish women. Fam Cancer 5:159–167. doi:10.1007/s10689-005-3871-7

    Article  PubMed  Google Scholar 

  3. Andrulis IL, Anton-Culver H, Beck J et al (2002) Comparison of DNA- and RNA-based methods for detection of truncating BRCA1 mutations. Hum Mutat 20:65–73. doi:10.1002/humu.10097

    Article  PubMed  CAS  Google Scholar 

  4. Ganguly A, Rock MJ, Prockop DJ (1993) Conformation-sensitive gel electrophoresis for rapid detection of single-base differences in double-stranded PCR products and DNA fragments: evidence for solvent-induced bends in DNA heteroduplexes. Proc Natl Acad Sci USA 90:10325–10329. doi:10.1073/pnas.90.21.10325

    Article  PubMed  CAS  Google Scholar 

  5. Korkko J, Annunen S, Pihlajamaa T et al (1998) Conformation sensitive gel electrophoresis for simple and accurate detection of mutations: comparison with denaturing gradient gel electrophoresis and nucleotide sequencing. Proc Natl Acad Sci USA 95:1681–1685. doi:10.1073/pnas.95.4.1681

    Article  PubMed  CAS  Google Scholar 

  6. Frank TS, Deffenbaugh AM, Reid JE et al (2002) Clinical characteristics of individuals with germline mutations in BRCA1 and BRCA2: analysis of 10,000 individuals. J Clin Oncol 20:1480–1490. doi:10.1200/JCO.20.6.1480

    Article  PubMed  CAS  Google Scholar 

  7. Keogh LA, Southey MC, Maskiell J et al (2004) Uptake of offer to receive genetic information about BRCA1 and BRCA2 mutations in an Australian population-based study. Cancer Epidemiol Biomarkers Prev 13:2258–2263

    PubMed  Google Scholar 

  8. Goldgar DE, Easton DF, Deffenbaugh AM et al (2004) Integrated evaluation of DNA sequence variants of unknown clinical significance: application to BRCA1 and BRCA2. Am J Hum Genet 75:535–544. doi:10.1086/424388

    Article  PubMed  CAS  Google Scholar 

  9. Walsh T, Casadei S, Coats KH et al (2006) Spectrum of mutations in BRCA1, BRCA2, CHEK2, and TP53 in families at high risk of breast cancer. JAMA 295:1379–1388. doi:10.1001/jama.295.12.1379

    Article  PubMed  CAS  Google Scholar 

  10. Smith LD, Tesoriero AA, Ramus SJ et al (2007) BRCA1 promoter deletions in young women with breast cancer and a strong family history: a population-based study. Eur J Cancer 43:823–827. doi:10.1016/j.ejca.2007.01.011

    Article  PubMed  CAS  Google Scholar 

  11. Tavtigian SV, Deffenbaugh AM, Yin L et al (2006) Comprehensive statistical study of 452 BRCA1 missense substitutions with classification of eight recurrent substitutions as neutral. J Med Genet 43:295–305. doi:10.1136/jmg.2005.033878

    Article  PubMed  CAS  Google Scholar 

  12. Chen X, Truong TT, Weaver J et al (2006) Intronic alterations in BRCA1 and BRCA2: effect on mRNA splicing fidelity and expression. Hum Mutat 27:427–435. doi:10.1002/humu.20319

    Article  PubMed  CAS  Google Scholar 

  13. Abkevich V, Zharkikh A, Deffenbaugh AM et al (2004) Analysis of missense variation in human BRCA1 in the context of interspecific sequence variation. J Med Genet 41:492–507. doi:10.1136/jmg.2003.015867

    Article  PubMed  CAS  Google Scholar 

  14. Easton DF, Deffenbaugh AM, Pruss D et al (2007) A systematic genetic assessment of 1,433 sequence variants of unknown clinical significance in the BRCA1 and BRCA2 breast cancer-predisposition genes. Am J Hum Genet 81:873–883. doi:10.1086/521032

    Article  PubMed  CAS  Google Scholar 

  15. Ozcelik H, Knight JA, Glendon G et al (2003) Individual and family characteristics associated with protein truncating BRCA1 and BRCA2 mutations in an Ontario population based series from the Cooperative Family Registry for Breast Cancer Studies. J Med Genet 40:e91. doi:10.1136/jmg.40.8.e91

    Article  PubMed  CAS  Google Scholar 

  16. Southey MC, Tesoriero AA, Andersen CR et al (1999) BRCA1 mutations and other sequence variants in a population-based sample of Australian women with breast cancer. Br J Cancer 79:34–39. doi:10.1038/sj.bjc.6690008

    Article  PubMed  CAS  Google Scholar 

  17. John EM, Miron A, Gong G et al (2007) Prevalence of pathogenic BRCA1 mutation carriers in 5 US racial/ethnic groups. JAMA 298:2869–2876. doi:10.1001/jama.298.24.2869

    Article  PubMed  CAS  Google Scholar 

  18. Whittemore AS, Gong G, John EM et al (2004) Prevalence of BRCA1 mutation carriers among U.S. non-Hispanic Whites. Cancer Epidemiol Biomarkers Prev 13:2078–2083

    PubMed  CAS  Google Scholar 

  19. Haile RW, Thomas DC, McGuire V et al (2006) BRCA1 and BRCA2 mutation carriers, oral contraceptive use, and breast cancer before age 50. Cancer Epidemiol Biomarkers Prev 15:1863–1870. doi:10.1158/1055-9965.EPI-06-0258

    Article  PubMed  CAS  Google Scholar 

  20. McGuire V, John EM, Felberg A et al (2006) No increased risk of breast cancer associated with alcohol consumption among carriers of BRCA1 and BRCA2 mutations ages <50 years. Cancer Epidemiol Biomarkers Prev 15:1565–1567. doi:10.1158/1055-9965.EPI-06-0323

    Article  PubMed  CAS  Google Scholar 

  21. Breast Cancer Family Registry, Kathleen Cunningham Consortium for Research into Familial Breast Cancer (Australasia), Ontario Cancer Genetics Network (Canada) (2007) Smoking and risk of breast cancer in carriers of mutations in BRCA1 or BRCA2 aged less than 50 years. Breast Cancer Res Treat 109:67–75

    Google Scholar 

  22. Antoniou AC, Sinilnikova OM, Simard J et al (2007) RAD51 135G→C modifies breast cancer risk among BRCA2 mutation carriers: results from a combined analysis of 19 studies. Am J Hum Genet 81:1186–1200. doi:10.1086/522611

    Article  PubMed  CAS  Google Scholar 

  23. Couch FJ, Sinilnikova O, Vierkant RA et al (2007) AURKA F31I polymorphism and breast cancer risk in BRCA1 and BRCA2 mutation carriers: a consortium of investigators of modifiers of BRCA1/2 study. Cancer Epidemiol Biomarkers Prev 16:1416–1421. doi:10.1158/1055-9965.EPI-07-0129

    Article  PubMed  CAS  Google Scholar 

  24. Lee JS, John EM, McGuire V et al (2006) Breast and ovarian cancer in relatives of cancer patients, with and without BRCA mutations. Cancer Epidemiol Biomarkers Prev 15:359–363. doi:10.1158/1055-9965.EPI-05-0687

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by the National Cancer Institute, National Institutes of Health under RFA # CA-95-011 and through cooperative agreements with members of the Breast Cancer Family Registry and Principal Investigators, including Cancer Care Ontario (U01 CA69467), Columbia University (U01 CA69398), Fox Chase Cancer Center (U01 CA69631), Huntsman Cancer Institute (U01 CA69446), Huntsman Cancer Institute (U01 CA69446), Northern California Cancer Center (U01 CA69417), University of Melbourne (U01 CA69638), and Research Triangle Institute Informatics Support Center (RFP No. N02PC45022-46). Mutation testing in Australia was supported by grants from the National Health and Medical Research Council (NHMRC) and the Victorian Breast Cancer Research Consortium (VBCRC). Mutation testing at Fox Chase Cancer Center was in part supported by an Ovarian Cancer SPORE grant (P50 CA83638). Mutation testing in Ontario was supported in part by Cancer Care Ontario. We wish to thank members of the Ontario Cancer Genetics Network for their contributions to the study. MCS is a Senior Research Fellow of the NHMRC and JLH is an Australia Fellow and a VBCRC Group Leader. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast CFR, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government or the Breast CFR.

Author information

Authors and Affiliations

  1. Department of Epidemiology, University of California Irvine, Irvine, CA, 92697-7550, USA

    Susan L. Neuhausen

  2. Division of Epidemiology and Biostatistics, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada

    Hilmi Ozcelik

  3. Department of Pathology, The University of Melbourne, Parkville, VIC, Australia

    Melissa C. Southey

  4. Northern California Cancer Center, Fremont, CA, USA

    Esther M. John

  5. Fox Chase Cancer Center, Philadelphia, PA, USA

    Andrew K. Godwin & Mary B. Daly

  6. Department of Pediatrics and Medicine, Columbia University, New York, NY, USA

    Wendy Chung

  7. Research Triangle Institute, Raleigh, NC, USA

    Jeniffer Iriondo-Perez

  8. Department of Cancer Biology, Dana Farber Cancer Center, Boston, MA, USA

    Alexander Miron

  9. Mailman School of Public Health, Columbia University, New York, NY, USA

    Regina M. Santella, Ruby T. Senie & Mary Beth Terry

  10. Stanford University School of Medicine, Palo Alto, CA, USA

    Alice Whittemore

  11. Ontario Cancer Genetics Network, Cancer Care Ontario, Fred A. Litwin Center for Cancer Genetics, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada

    Irene L. Andrulis

  12. Huntsman Cancer Institute at the University of Utah, Salt Lake City, UT, USA

    Saundra S. Buys

  13. Center for Molecular, Environmental, Genetic and Analytic Epidemiology, The University of Melbourne, Parkville, VIC, Australia

    John L. Hopper

  14. Epidemiology and Genetics Research Program, Clinical and Genetic Epidemiology Research Branch, Division of Cancer Control and Population Sciences, National Cancer Institute, Bethesda, MD, USA

    Daniela Seminara

Authors
  1. Susan L. Neuhausen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hilmi Ozcelik
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Melissa C. Southey
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Esther M. John
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Andrew K. Godwin
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Wendy Chung
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jeniffer Iriondo-Perez
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Alexander Miron
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Regina M. Santella
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Alice Whittemore
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Irene L. Andrulis
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Saundra S. Buys
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Mary B. Daly
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. John L. Hopper
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Daniela Seminara
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Ruby T. Senie
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Mary Beth Terry
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

Breast Cancer Family Registry

Corresponding author

Correspondence to Susan L. Neuhausen.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Neuhausen, S.L., Ozcelik, H., Southey, M.C. et al. BRCA1 and BRCA2 mutation carriers in the Breast Cancer Family Registry: an open resource for collaborative research. Breast Cancer Res Treat 116, 379–386 (2009). https://doi.org/10.1007/s10549-008-0153-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-008-0153-8

Keywords

Search

Navigation