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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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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