The carrier frequency of the BRCA1 185delAG mutation is approximately 1 percent in Ashkenazi Jewish individuals

Article metrics

  • A Correction to this article was published on 01 January 1996


Since BRCA1, the first major gene responsible for inherited breast cancer, was cloned1, more than 50 unique mutations have been detected in the germline of individuals with breast and ovarian cancer1‐10. In high-risk pedigrees, female carriers of BRCA1 mutations have an 80–90% lifetime risk of breast cancer11, and a 40–50% risk of ovarian cancer12. However, the mutation status of individuals unselected for breast or ovarian cancer has not been determined, and it is not known whether mutations in such individuals confer the same risk of cancer as in individuals from the high-risk families studied so far. Following the finding of a 185delAG frameshift mutation in several Ashkenazi Jewish breast/ovarian families8,9,13, we have determined the frequency of this mutation in 858 Ashkenazim seeking genetic testing for conditions unrelated to cancer, and in 815 reference individuals not selected for ethnic origin. We observed the 185delAG mutation in 0.9% of Ashkenazim (95% confidence limit, 0.4%–1.8%) and in none of the reference samples. Our results suggest that one in a hundred women of Ashkenazi descent may be at especially high risk of developing breast and/or ovarian cancer.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.


  1. 1

    Miki, Y. et al. A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science 266, 66–71 (1994).

  2. 2

    Futreal, P.A. et al. BRCA1 mutations in primary breast and ovarian carcinomas. Science 266, 120–122 (1994).

  3. 3

    Castilla, L.H. et al. Mutations in the BRCAl gene in families with early-onset breast and ovarian cancer. Nature Genet. 8, 387–391 (1994).

  4. 4

    Simard, J. et al. Common origins of BRCA1 mutations in Canadian breast and ovarian cancer families. Nature Genet. 8, 392–398 (1994).

  5. 5

    Friedman, L.S. et al. Confirmation of BRCA1 by analysis of germline mutations linked to breast and ovarian cancer in ten families. Nature Genet. 8, 399–404 (1994).

  6. 6

    Shattuck-Eidens, D. et al. A collaborative survey of 80 mutations in the BRCA1 breast and ovarian cancer susceptibility gene. Implications for presymptomatic testing and screening. J. Am. med. Assoc. 273, 535–541 (1995).

  7. 7

    Hogervorst, F.B.L. et al. Rapid detection of BRCA1 mutations by the protein truncation test. Nature Genet. 10, 208–212 (1995).

  8. 8

    Struewing, J.P. et al. Detection of eight BRCA1 mutations in 10 breast/ovarian cancer families, including one family with male breast cancer. Am. J. hum. Genet. 57, 1–7 (1995).

  9. 9

    Takahashi, H. et al. Mutation analysis of the BRCA1 gene in ovarian cancers. Cancer Res. 56, 2998–3002 (1995).

  10. 10

    Inoue, R. et al. Germline mutation of BRCA1 in Japanese breast cancer families. Cancer Res. 55, 3521–3524 (1995).

  11. 11

    Easton, D.F. et al. Genetic linkage analysis in familial breast and ovarian cancer: results from 214 families. Am. J. hum. Genet. 52, 678–701 (1993).

  12. 12

    Ford, D., Easton, D.F., Bishop, D.T., Narod, S.A. & Goldgar, D.E. and the Breast Cancer Linkage Consortium. Risks of cancer in BRCA1-mutation carriers. Lancet 343, 692–695 (1994).

  13. 13

    Tonin, P. et al. BRCA1 mutations in Ashkenazi Jewish women. Am. J. hum. Genet 57, 189 (1995).

  14. 14

    Wingo, P.A., Tong, T. & Bolden, S. Cancer statistics, 1995. Cancer J. Clin. 45, 8–30 (1995).

  15. 15

    Ottman, R., Pike, M.C., King, M.C., Casagrande, J.T. & Henderson, B. Familial breast cancer in a population-based series. Am. J. Epidemiol. 123, 15–21 (1986).

  16. 16

    Claus, E.B., Risch, N. & Thompson, W.D. Genetic ananlysis of breast cancer in the Cancer and Steroid Hormone Study. Am. J. hum. Genet. 48, 232–242 (1991).

  17. 17

    Newman, B., Austin, M.A., Lee, M. & King, M.C. Inheritance of human breast cancer: evidence for autosomal dominant transmission in high-risk families. Proc. natn. Acad. Sci. U.S.A. 85, 3044–3048 (1988).

  18. 18

    Narod, S.A. et al. An evaluation of genetic heterogeneity in 145 breast-ovarian cancer families. Breast Cancer Linkage Consortium. Am. J. hum. Genet. 56, 254–264 (1995).

  19. 19

    Kelsey, J.L. et al. Exogenous estrogens and otherfactors in the epidemiology of breast cancer. J. natn. Cancer Inst. 67, 327–333 (1981).

  20. 20

    Westin, J.B. & Richter, E., The Israeli breast-cancer anomaly. Ann. N. Y. Acad. Sci. 609, 269–79 (1990).

  21. 21

    Motulsky, A.G. Jewish diseases and origins. Nature Genet. 9, 99–101 (1995).

  22. 22

    Marquis, S.T. et al. The developmental pattern of Brcal expression implies a role in differentiation of the breast and other tissues. Nature Genet. 11, 17–26 (1995).

  23. 23

    Risch, N. et al. Genetic analysis of idiopathic torsion dystonia in Ashkenazi Jews and their recent descent from a small founder population. Nature Genet. 9, 152–159 (1995).

  24. 24

    Assessing Genetic Risks: Implications for Health and Policy(eds Andrews, L. B., Fullarton, J. E., Holtzman, N. A., Motulsky, A. G.) (National Academy Press, Washington, D.C., 1994).

  25. 25

    Biesecker, B.B. et al. Genetic counseling for families with inherited susceptibility to breast and ovarian cancer. J. Am. med. Assoc. 269, 1970–1974 (1993).

  26. 26

    National Center for Human Genome Research. Statement on use of DNA testing for presymptomatic identification of cancer risk. J. Am. med. Assoc. 271, 785 (1994).

  27. 27

    National Breast Cancer Coalition. Presymptomatic genetic testing for heritable breast cancer risk. Press Release (1994).

  28. 28

    National Advisory Council for Human Genome Research. Statement on use of DNA testing for presymptomatic identification of cancer risk. J. Am. med. Assoc. 71, 785 (1994).

  29. 29

    Statement of the American Society of Human Genetics on genetic testing for breast and ovarian cancer predisposition. Am. J. hum. Genet. 55, i–iv (1994).

  30. 30

    Hoskins, K.F. et al. Assessment and counseling for women with a family history of breast cancer. A guide for clinicians. J. Am. med. Assoc. 273, 577–585 (1995).

  31. 31

    DelPergola, S. in Genetic Diversity Among the Jews. (eds Bonne-Tamir & Adam, A.) 3–30 (Oxford University Press, 1992).

  32. 32

    Raben, N., Sherman, J., Miller, F., Mena, H. & Plotz, P. A 5′ splice junction mutation leading to exon deletion in an Ashkenazic Jewish family with phosphofructokinase deficiency (Tarui disease). J. Biol. Chem 268, 4963–4967 (1993).

  33. 33

    Haldane, J.B.S. The ratio of spontaneous mutation of a human gene. J. Genet. 31, 317–326 (1935).

  34. 34

    Feuer, E.J. et al. The lifetime risk of developing breast cancer. J. natn. Cancer Inst. 85, 892–897 (1993).

  35. 35

    Miller, B.A. et al. SEER Cancer Statistics Review: 1973–1990, National Cancer Institute. NIH Pub. No. 93–2789 (1993).

Download references

Author information

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Struewing, J., Abeliovich, D., Peretz, T. et al. The carrier frequency of the BRCA1 185delAG mutation is approximately 1 percent in Ashkenazi Jewish individuals. Nat Genet 11, 198–200 (1995) doi:10.1038/ng1095-198

Download citation

Further reading