Brief Communication | Published:

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

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.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1

    Shiloh, Y. Nat. Rev. Cancer 3, 155–168 (2003).

  2. 2

    Swift, M. et al. N. Engl. J. Med. 316, 1289–1294 (1987).

  3. 3

    Thompson, D. et al. J. Natl. Cancer Inst. 97, 813–822 (2005).

  4. 4

    Fitzgerald, M.G. et al. Nat. Genet. 15, 307–310 (1997).

  5. 5

    Teraoka, S.N. et al. Cancer 92, 479–487 (2001).

  6. 6

    Sommer, S.S. et al. Cancer Genet. Cytogenet. 145, 115–120 (2003).

  7. 7

    Gatti, R.A. et al. Mol. Genet. Metab. 68, 419–423 (1999).

  8. 8

    Chenevix-Trench, G. et al. J. Natl. Cancer Inst. 94, 205–215 (2002).

  9. 9

    Olsen, R.H. et al. Br. J. Cancer 93, 260–265 (2005).

  10. 10

    Meijers-Heijboer, H. et al. Nat. Genet. 31, 55–59 (2002).

  11. 11

    CHEK2 breast cancer case-control consortium. Am. J. Hum. Genet. 74, 1175–1182 (2004).

  12. 12

    Antoniou, A.C. et al. Genet. Epidemiol. 25, 190–202 (2003).

  13. 13

    Becker-Catania, S.G. et al. Mol. Genet. Metab. 70, 122–133 (2000).

Download references

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.

Author information

Competing interests

The authors declare no competing financial interests.

Correspondence to Nazneen Rahman.

Supplementary information

  1. Supplementary Table 1

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

  2. Supplementary Table 2

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

  3. Supplementary Methods (PDF 28 kb)

  4. Supplementary Note (PDF 24 kb)

Rights and permissions

Reprints and Permissions

About this article

Further reading

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