The carrier frequency of the BRCA2 6174delT mutation among Ashkenazi Jewish individuals is approximately 1% (original) (raw)

Nature Genetics volume 14, pages 188–190 (1996)Cite this article

Abstract

Certain germline mutations in either BRCA1 or BRCA2 confer a lifetime risk of developing breast cancer that may approach 90% 1–3. The BRCA1 185delAG mutation was found in 20% and the BRCA2 6174delT mutation in 8% of Ashkenazi Jewish women with early-onset breast cancer4–6. The 185delAG mutation was observed in 0.9% of 858 Ashkenazi Jews unselected for a personal or family history of cancer7. Assuming comparable age-specific penetrances, a carrier frequency of 0.3% was estimated for the 6174delT BRCA2 mutation6. To test this hypothesis, we performed a population survey of 1,255 Jewish individuals. In two independent groups, a prevalence of approximately 1 % (C.I. 0.6–1.5) was observed for the 6174delT mutation. The relative risk of developing breast cancer by age 42 was estimated to be 9.3 (C.I. 2.5–22.5) for6174delT, compared to 31 (C.I. 11–77) for 185delAG. Analysis of 107 Ashkenazi Jewish women with breast cancer and a family history of breast or ovarian cancer confirmed a four-fold greater prevalence for the BRCA1 185delAG mutation compared to the BRCA2 6174delT mutation. Our findings suggest a difference in cumulative lifetime penetrance for the two mutations. Genetic counseling for the one in 50 Ashkenazi Jewish individuals harbouring specific germline mutations in BRCA1 or BRCA2 must be tailored to reflect the different risks associated with the two mutations.

This is a preview of subscription content, access via your institution

Access options

Subscribe to this journal

Receive 12 print issues and online access

$209.00 per year

only $17.42 per issue

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Additional access options:

Similar content being viewed by others

References

  1. Easton, D. et al. Genetic linkage analysis in familial breast and ovarian cancer: results from 214 families. Am. J. Hum Genet. 52, 678–701 (1993).
    CAS PubMed PubMed Central Google Scholar
  2. Wooster, R. et al. Localization of a breast cancer susceptibility gene, BRCA2, to chromosome 13q12–13. Science 265, 2088–2090 (1994).
    Article CAS Google Scholar
  3. Miki, Y. et al. A strong candidate gene for the breast and ovarian cancer susceptibility gene BRCA1. Science 266, 66–71 (1994).
    Article CAS Google Scholar
  4. FitzGerald, M.G. et al. Germ-line BRCA1 mutations in Jewish and non-Jewish women with early-onset breast cancer. N. Engl. J. Med. 334, 143–149 (1996).
    Article CAS Google Scholar
  5. Offit, K. et al. Germline BRCA1 185delAG mutations in Jewish women affected by breast cancer. Lancet 347, 1643–1645 (1996).
    Article CAS Google Scholar
  6. Neuhausen, S. et al. Recurrent BRCA2 6174delT mutations in Ashkenazi Jewish women affected by breast cancer. Nature Genet. 13, 126–128 (1996).
    Article CAS Google Scholar
  7. Struewing, J.P. et al.The carrier frequency of the BRCA1 185delAG mutation is approximately 1 percent in Ashkenazi Jewish individuals. Nature Genet. 11, 198–200 (1995).
    Article CAS Google Scholar
  8. Wooster, R. et al. Identification of the breast cancer susceptibility gene BRCA2. Nature 378, 789–792 (1995).
    Article CAS Google Scholar
  9. Tavtigian, S.V. et al. The BRCA2 gene and mutations in 13q-linked kindreds. Nature Genet. 12, 333–337 (1996).
    Article CAS Google Scholar
  10. Simard, J. et al. Common origins of BRCA1 mutations in Canadian breast and ovarian cancer families. Nature Genet. 8, 392–398 (1994).
    Article CAS Google Scholar
  11. Struewing, J.P. et al Detection of eight BRCA1 mutations in 10 breast ovarian cancer families including 1 family with male breast cancer Am.J.Hum Genet. 57, 1–7 (1995).
    Article CAS Google Scholar
  12. Tonin, P. et al.BRCA1 mutations in Ashkenazi Jewish Women. Am. J. Hum Genet. 57, 189 (1995).
    CAS PubMed PubMed Central Google Scholar
  13. Berman, D.B., Wagner-Costalas, J., Schultz, D.C., Lynch, H.T., Daly, M. & Godwin, A.K. Two distinct origins of a common BRCA1 mutation in breast ovarian cancer families: a genetic study of 15185delAG-mutation kindreds. Am.J.Hum Genet 58, 1166–1176 (1996).
    CAS PubMed PubMed Central Google Scholar
  14. Neuhausen, S.L. et al. Haplotypeand phenotype analysis of six recurrent BRCA1 mutations in 61 families: results of an international study. Am. J. Hum Genet. 58, 271–280, (1996).
    CAS PubMed PubMed Central Google Scholar
  15. Kronn, D., Oddoux, C., Phillips, J. & Ostrer, H. The frequency of carriers for Canavan disease in the metropolitan New York Ashkenazi Jewish population. Am. J. Hum Genet. 57, 1250–1252, (1995).
    CAS PubMed PubMed Central Google Scholar
  16. Oddoux, C. et al. Prenatal diagnostic testing for familial dysautonomia using linked genetic markers. Prenat. Diagn. 15, 817–826 (1995).
    Article CAS Google Scholar

Download references

Author information

Authors and Affiliations

  1. Human Genetics Program, Department of Pediatrics, New York University Medical Center, New York, New York, 10016, USA
    Carole Oddoux, C. Mark Clayton & Harry Ostrer
  2. Genetic Epidemiology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, 20892, USA
    Jeffery P. Struewing
  3. Genetic Epidemiology Group, Department of Medical Informatics, University of Utah School of Medicine, Salt Lake City, Utah, 84108, USA
    Susan Neuhausen
  4. Laboratory of Gene Transfer, National Center for Human Genome Research, National Institutes of Health, Bethesda, Maryland, 20892, USA
    Lawrence C. Brody
  5. Departmentof Pediatrics and Reproductive Medicine, University of California, San Diego, San Diego, California, 92123, USA
    Michael Kaback
  6. Department of Human Genetics, Memorial Sloan-Kettering Cancer Center, New York, New York, 10021, USA
    Bruce Haas, Suresh Jhanwar & Kenneth Offit
  7. Breast Cancer Medicine Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York, 10021, USA
    Larry Norton
  8. Breast Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York, 10021
    Patrick Borgen
  9. Unit of Genetic Epidemiology, International Agency for Research on Cancer, Lyon, Cedex 08, France
    David Goldgar

Authors

  1. Carole Oddoux
    You can also search for this author inPubMed Google Scholar
  2. Jeffery P. Struewing
    You can also search for this author inPubMed Google Scholar
  3. C. Mark Clayton
    You can also search for this author inPubMed Google Scholar
  4. Susan Neuhausen
    You can also search for this author inPubMed Google Scholar
  5. Lawrence C. Brody
    You can also search for this author inPubMed Google Scholar
  6. Michael Kaback
    You can also search for this author inPubMed Google Scholar
  7. Bruce Haas
    You can also search for this author inPubMed Google Scholar
  8. Larry Norton
    You can also search for this author inPubMed Google Scholar
  9. Patrick Borgen
    You can also search for this author inPubMed Google Scholar
  10. Suresh Jhanwar
    You can also search for this author inPubMed Google Scholar
  11. David Goldgar
    You can also search for this author inPubMed Google Scholar
  12. Harry Ostrer
    You can also search for this author inPubMed Google Scholar
  13. Kenneth Offit
    You can also search for this author inPubMed Google Scholar

Corresponding author

Correspondence toHarry Ostrer.

Rights and permissions

About this article

Cite this article

Oddoux, C., Struewing, J., Clayton, C. et al. The carrier frequency of the BRCA2 6174delT mutation among Ashkenazi Jewish individuals is approximately 1%.Nat Genet 14, 188–190 (1996). https://doi.org/10.1038/ng1096-188

Download citation