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ATM mutations that cause ataxia-telangiectasia are breast cancer susceptibility alleles

Nature Genetics volume 38, pages 873–875 (2006)Cite this article

Abstract

We screened individuals from 443 familial breast cancer pedigrees and 521 controls for ATM sequence variants and identified 12 mutations in affected individuals and two in controls (P = 0.0047). The results demonstrate that ATM mutations that cause ataxia-telangiectasia in biallelic carriers are breast cancer susceptibility alleles in monoallelic carriers, with an estimated relative risk of 2.37 (95% confidence interval (c.i.) = 1.51–3.78, P = 0.0003). There was no evidence that other classes of ATM variant confer a risk of breast cancer.

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Figure 1: Abridged pedigrees of twelve breast cancer families with ATM mutations.

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Acknowledgements

We thank the participating families who were recruited to the study by the Familial Breast Cancer Collaboration (UK), which includes the following contributors: A. Ardern-Jones, J. Berg, A. Brady, N. Bradshaw, C. Brewer, G. Brice, B. Bullman, J. Campbell, B. Castle, R. Cetnarsryj, C. Chapman, C. Chu, N. Coates, T. Cole, R. Davidson, A. Donaldson, H. Dorkins, F. Douglas, D. Eccles, R. Eeles, F. Elmslie, D.G. Evans, S. Goff, S. Goodman, D. Goudie, J. Gray, L. Greenhalgh, H. Gregory, N. Haites, S.V. Hodgson, T. Homfray, R.S. Houlston, L. Izatt, L. Jeffers, V. Johnson-Roffey, F. Kavalier, C. Kirk, F. Lalloo, I. Locke, M. Longmuir, J. Mackay, A. Magee, S. Mansour, Z. Miedzybrodzka, J. Miller, P. Morrison, V. Murday, J. Paterson, M. Porteous, N. Rahman, M. Rogers, S. Rowe, S. Shanley, A. Saggar, G. Scott, L. Side, L. Snadden, M. Steel, M. Thomas, S. Thomas. We thank A. Hall and E. Mackie for coordination of sample collection. We acknowledge use of DNA from the British 1958 Birth Cohort collection, funded by the Medical Research Council grant G0000934 and the Wellcome Trust grant 068545/Z/02. M. Ahmed and B. North are supported by the US Army Medical Research and Material Command grant #W81XWH-05-1-0204. This research was supported by the Institute of Cancer Research and by grants from the Breast Cancer Campaign and Cancer Research UK.

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Authors and Affiliations

  1. Section of Cancer Genetics, Institute of Cancer Research, 15 Cotswold Road, Sutton, SM2 5NG, Surrey, UK

    Anthony Renwick, Sheila Seal, Patrick Kelly, Tasnim Chagtai, Munaza Ahmed, Bernard North, Hiran Jayatilake, Rita Barfoot, Katarina Spanova, Michael R Stratton & Nazneen Rahman

  2. Cancer Research UK, Genetic Epidemiology Unit, Strangeways Research Laboratories, University of Cambridge, CB1 8RN, UK

    Deborah Thompson, Lesley McGuffog & Douglas F Easton

  3. Department of Medical Genetics, St Mary's Hospital, Manchester, M13 0JH, UK

    D Gareth Evans

  4. Wessex Clinical Genetics Service, Princess Anne Hospital, Southampton, SO16 6YA, UK

    Diana Eccles

  5. Cancer Genome Project, The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, CB10 1SA, Cambridge, UK

    Michael R Stratton

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  1. Anthony Renwick
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The Breast Cancer Susceptibility Collaboration (UK)

Corresponding author

Correspondence to Nazneen Rahman.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Table 1

Primers and PCR conditions for ATM coding exons. (PDF 68 kb)

Supplementary Table 2

Nonsynonymous ATM missense variants in breast cancer cases and controls. (PDF 58 kb)

Supplementary Methods (PDF 28 kb)

Supplementary Note (PDF 24 kb)

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Renwick, A., Thompson, D., Seal, S. et al. ATM mutations that cause ataxia-telangiectasia are breast cancer susceptibility alleles. Nat Genet 38, 873–875 (2006). https://doi.org/10.1038/ng1837

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