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A germline mutation in the androgen receptor gene in two brothers with breast cancer and Reifenstein syndrome

Nature Genetics volume 2, pages 132–134 (1992)Cite this article

Abstract

Breast cancer in men is rare — among the risk factors that have been identified are a family history of breast cancer and evidence of androgen insufficiency. We report a family in which two brothers who both developed breast cancer had clinical and endocrinological evidence of androgen resistance. Sequence analysis revealed a mutation in the androgen receptor gene on the X chromosome, within the region encoding the DNA binding domain. This is the first report of a germline mutation in a member of the steroid/thyroid hormone receptor superfamily associated with the development of cancer.

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References

  1. Crichlow, R.W. & Galt, S.W. Male breast cancer. Surg. Clinics N. America 70, 1165–1177 (1990).

    Article  CAS  Google Scholar 

  2. Rose, D.P. Endocrine epidemiology of male breast cancer. Anticancer Res. 8, 845–850 (1988).

    CAS  PubMed  Google Scholar 

  3. Thomas, D.B. et al. Breast cancer in men: risk factors with hormonal implications. Am. J. Epidemiol. 135, 734–748 (1992).

    Article  CAS  Google Scholar 

  4. Rosenblatt, K.A. et al. Breast cancer in men: aspects of familial aggregation. J. natl. Cancer Inst. 83, 849–853 (1991).

    Article  CAS  Google Scholar 

  5. Lenfant-Pejovic, M.-H., Mlika-Cabanne, N., Bouchardy, C. & Auquier, A. Risk factors for male breast cancer: a Franco-Swiss case control study. Int. J. Cancer 45, 661–665 (1990).

    Article  CAS  Google Scholar 

  6. Malkin, D. et al. Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms. Science 250, 1233–1238 (1990).

    Article  CAS  Google Scholar 

  7. Hall, J.M. et al. Linkage of early onset familial breast cancer to chromosome 17q21. Science 250, 1684–1689 (1990).

    Article  CAS  Google Scholar 

  8. Griffin, J.E. Androgen resistance-the clinical and molecular spectrum. N. Eng. J. Med. 326, 611–618 (1992).

    Article  CAS  Google Scholar 

  9. McPhaul, M.J. et al. Molecular basis of androgen resistance in a family with a qualitative abnormality of the androgen receptor and responsive to high dose androgen therapy. J. clin. Invest. 87, 1413–1421 (1991).

    Article  CAS  Google Scholar 

  10. LaSpada, A.R., Wilson, E., Lubahn, D.B., Harding, A.E. & Fischbeck, K.H. Androgen receptor gene mutations in X-linked spinal and bulbar muscular atrophy. Nature 352, 77–79 (1991).

    Article  CAS  Google Scholar 

  11. Harris, E.L. Genetic epidemiology of hypospadias. Epidemiol. Rev. 12, 29–40 (1990).

    Article  CAS  Google Scholar 

  12. Frydman, M., Grieber, C. & Cohen, H.A. Uncomplicated familial hypospadias: Evidence for autosomal recessive inheritance. Am. J. med. Genet. 21, 51–55 (1985).

    Article  CAS  Google Scholar 

  13. Evans, R.M. The steroid and thyroid hormone receptor family. Science 240, 889–895 (1988).

    Article  CAS  Google Scholar 

  14. Verp, M.S. & Simpson, J.L. Abnormal sexual differentiation and neoplasia. Cancer Genet. Cytogenet. 25, 191–218 (1987).

    Article  CAS  Google Scholar 

  15. Pelletier, J. et al. WT1 mutations contribute to to abnormal genital system development and hereditary Wilms tumour. Nature 353, 431–434 (1991).

    Article  CAS  Google Scholar 

  16. Pelletier, J. et al. Germline mutations in the Wilms tumor suppressor gene are associated with abnormal urogenital development in Denys-Drash syndrome. Cell 67, 437–447 (1991).

    Article  CAS  Google Scholar 

  17. Green, S., Kumar, V., Theulaz, I., Wahli, W. & Chambon, P. The N-terminal DNA-binding “zinc finger” of the oestrogen and glucocorticoid receptors determines target gene specificity. EMBO J. 7, 3037–3044 (1988).

    Article  CAS  Google Scholar 

  18. Mader, S., Kumar, V., de Verneuil, H. & Chambon, P. Three amino acids of the oestrogen receptor are essential to its ability to distinguish an oestrogen from a glucocorticoid-response element. Nature 338, 271–274 (1989).

    Article  CAS  Google Scholar 

  19. Schena, M., Freedman, L.P. & Yamamoto, K.R. Mutations in the glucocorticoid receptor zinc finger region that distinguish interdigitated DNA binding and transcriptional enhancement activties. Genes Dev. 3, 1590–1601 (1989).

    Article  CAS  Google Scholar 

  20. Demeter, J.G., Waterman, N.G. & Verdi, G.D. Familial male breast carcinoma. Cancer 65, 2342–2343 (1990).

    Article  CAS  Google Scholar 

  21. Everson, R.B., Fraumeni, J.F. & Wilson, R.E. Familial male breast cancer. Lancet 1, 9–12 (1976).

    Article  CAS  Google Scholar 

  22. Kozak, F.K., Hall, J.G. & Baird, P.A. Familial breast cancer in males. Cancer 58, 2736–2739 (1986).

    Article  CAS  Google Scholar 

  23. Marger, D., Urdaneta, N. & Fischer, J.J. Breast cancer in brothers. Cancer 36, 458–461 (1975).

    Article  CAS  Google Scholar 

  24. Teasdale, C., Forbes, J.F. & Baum, M. Familial male breast cancer. Lancet i, 361–362 (1976).

    Google Scholar 

Download references

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Authors and Affiliations

  1. Section of Molecular Carcinogenesis and CRC Section of Epidemiology, The Institute of Cancer Research, 15 Cotswold Road, Belmont, Sutton, Surrey, SM2 5NG, UK

    Richard Wooster, Jonathan Mangion, Rosalind Eeles, Diane Averill, Douglas F. Easton & Michael R. Stratton

  2. Academic Unit of Radiotherapy, The Royal Marsden Hospital, Downs Road, Sutton, Surrey, SM2 5PT, UK

    Peter Barrett-Lee

  3. CRC Human Cancer Genetics Research Group, Department of Pathology, University of Cambridge, Tennis Court Rd, Cambridge, CB2 1QP, UK

    Simon Smith & Bruce A.J. Ponder

  4. Department of Biochemistry, The Royal Marsden Hospital, Fulham Rd, London, SW3, UK

    Mitchell Dowsett

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  1. Richard Wooster
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  2. Jonathan Mangion
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  3. Rosalind Eeles
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  4. Simon Smith
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  5. Mitchell Dowsett
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  6. Diane Averill
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  7. Peter Barrett-Lee
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  8. Douglas F. Easton
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  9. Bruce A.J. Ponder
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  10. Michael R. Stratton
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Wooster, R., Mangion, J., Eeles, R. et al. A germline mutation in the androgen receptor gene in two brothers with breast cancer and Reifenstein syndrome. Nat Genet 2, 132–134 (1992). https://doi.org/10.1038/ng1092-132

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