Abstract
Breast cancer in men is about a hundredfold less common than in women and this has hindered research into its genetic basis. We have examined 22 families with at least one case of male breast cancer for linkage to the hereditary breast and ovarian cancer locus, BRCA1, on chromosome 17q. We found strong evidence against linkage to BRCA1 (lod score – 16.63) and the best estimate of the proportion of linked families was 0% (95% Cl 0–18%). Our results indicate that there is a gene(s) other than BRCA1 which predisposes to early–onset breast cancer in women and which confers a higher risk of male breast cancer. Identification of additional pedigrees that include cases of male breast cancer may therefore facilitate the mapping and isolation of this gene.
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
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Thomas, D.B. Male breast cancer. Epidem. Rev. 15, 220–231 (1993).
Thomas, D.B. et al. Breast cancer in men: risk factors with hormonal implications. Am. J. Epidemiol. 135, 734–748 (1992).
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).
Rosenblatt, K.A. et al. Breast cancer in men: aspects of familial aggregation. J. natn. Cancer Inst. 83, 849–853 (1991).
Anderson, D.E. & Badzioch, M.D. Breast cancer risks in relatives of male breast cancer patients. J. natn. Cancer Inst. 84,1114–1117 (1992).
Claus, E.B., Risch, N.J. & Thompson, W.D. Age at onset as an indicator of familial risk of breast cancer. Am. J. Epidemiol. 131, 961–972 (1990).
Claus, E.B., Risch, N.J. & Thompson, W.D. Genetic analysis of breast cancer in the Cancer and Steroid Hormone Study. Am. J. hum. Genet. 48, 232–242 (1991).
Demeter, J.G., Waterman, N.G. & Verdi, G.D. Familial male breast carcinoma. Cancer 65, 2342–2343 (1990).
Everson, R.B., Fraumeni, J.F. & Wilson, R.E. Familial male breast cancer. Lancet i, 9–12 (1976).
Kozak, F.K., Hall, J.G. & Baird, P.A. Familial breast cancer in males. Cancer 58, 2736–2739 (1986).
Marger, D., Urdaneta, N. & Fischer, J.J. Breast cancer in brothers. Cancer 36, 458–461 (1975).
Teasdale, C., Forbes, J.F. & Baum, M. Familial male breast cancer. Lancet i, 361–362 (1976).
Hall, J.M. et al. Linkage of early onset familial breast cancer to chromosome 17q21. Science 250, 1684–1689 (1990).
Narod, S.A. et al. Familial breast ovarian cancer locus on chromosome 17q12–23. Lancet 338, 82–83 (1991).
Easton, D.F., Bishop, D.T., Ford, D., Crockford, G.P. and the Breast Cancer Linkage Consortium. Genetic linkage analysis in familial breast and ovarian cancer: results from 214 families. Am. J. hum. Genet. 52, 678–701 (1993).
Flejter, W. et al. Multicolor FISH mapping with Alu-PCR amplified YAC clone DNA determines the order of markers in the BRCA1 region of chromosome 17q12–q21. Genomics 17, 624–631 (1993).
Anderson, L. et al. High density genetic map of the BRCA1region of chromosome 17q12–q21. Genomics 17, 618–623 (1993).
Abel, K. et al. A radiation hybrid map of the BRCA1 region of chromosome 17q12–q21. Genomics 17, 632–641 (1993).
Wooster, R. et al. A germline mutation in the androgen receptor gene in two brothers with breast cancer and Reifenstein syndrome. Nature Genet. 2, 132–134 (1992).
Lobaccaro, J.-M. et al. Male breast cancer and the androgen receptor gene. Nature Genet. 5, 109–110 (1993).
Arason, A., Darkardottir, R.B. & Egilsson, V. Linkage analysis of chromosome 17q markers and breast ovarian cancer in Icelandic families and possible relationship to prostate cancer. Am. J. hum. Genet. 52, 711–717 (1993).
Cohen, B.B., Porter, D.E., Wallace, M.R., Carothers, A. & Steel, C.M. Linkage of a major breast cancer gene to chromosome 17q12–21: results from 15 Edinburgh families. Am. J. hum. Genet. 52, 723–729 (1993).
Smith, S. et al. Genetic heterogeneity and localisation of a familial breast-ovarian cancer gene on chromosome 17q12–21. Am. J. hum. Genet. 52, 767–776 (1993).
Bowcock, A.M. et al. Thra-1 and D17S183 flank an interval of <4cM for the breast-ovarian cancer gene (BRCA1) on chromosome 17q21. Am.J.hum.Genet. 52, 718–722 (1993).
Hall, J.M. et al. Closing in a breast cancer gene on chromosone 17qAm. Am. J. hum. Genet. 50, 1235–1242 (1992).
Weber, J.M. et al. Dinucleotide repeat polymorphisms at the D17S250 and D17S261 loci. Nucl. Acids Res. 18, 4640 (1990).
Lawrence, D.J., Monaghan, P. & Gusterson, B.A. The development of the normal human breast. Oxford Rev. Repr. Biol. 13, 149–174 (1991).
Wilson, J.D. in Harrison's Principles of Internal Medicine, 11th edn (eds Braunwald, E. et al.) 1387–1840 (McGraw Hill Book Company, New York, 1987).
Lathrop, G.M., Lalouel, J.M., Julier, C. & Ott, J. Strategies for multilocus linkage analysis in humans. Proc. natn. Acad. Sci. U.S.A. 81, 3443–3446 (1984).
Easton, D.F., Ford, D. & Peto, J. Inherited susceptibility to breast cancer. Cancer Surveys (in the press).
Smith, C.A.B. Homogeneity test for linkage data. Proc. Soc. Int. Congress hum. Genet. 1, 212–213 (1961).
Ott, J. Analysis of human genetic linkage 200–203 (Johns Hopkins University Press, Baltimore, 1985).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Stratton, M., Ford, D., Neuhasen, S. et al. Familial male breast cancer is not linked to the BRCA1 locus on chromosome 17q. Nat Genet 7, 103–107 (1994). https://doi.org/10.1038/ng0594-103
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/ng0594-103
This article is cited by
-
Analyzing the effects of BRCA1/2 variants on mRNA splicing by minigene assay
Journal of Human Genetics (2023)
-
An updated review of epidemiology, risk factors, and management of male breast cancer
Medical Oncology (2021)
-
Germline investigation in male breast cancer of DNA repair genes by next-generation sequencing
Breast Cancer Research and Treatment (2019)
-
The Bermuda Triangle: The Pragmatics, Policies, and Principles for Data Sharing in the History of the Human Genome Project
Journal of the History of Biology (2018)
-
Effect of BRCA2 mutation on familial breast cancer survival: A systematic review and meta-analysis
Journal of Huazhong University of Science and Technology [Medical Sciences] (2015)