Cancer Research CTRC-AACR San Antonio Breast Cancer Symposium Translational Medicine Conference in Israel
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[Cancer Research 64, 840-843, February 1, 2004]
© 2004 American Association for Cancer Research

Advances in Brief

Are ATM Mutations 7271T->G and IVS10-6T->G Really High-Risk Breast Cancer-Susceptibility Alleles?

Csilla I. Szabo1, Mieke Schutte2, Annegien Broeks3, Jeanine J. Houwing-Duistermaat2, Yvonne R. Thorstenson4, Francine Durocher5, Rogier A. Oldenburg2,6, Marijke Wasielewski2, Fabrice Odefrey1, Deborah Thompson1, Arno N. Floore3, Jaennelle Kraan6, Jan G. M. Klijn2, Ans M. W. van den Ouweland2 the BRCA-X Consortium8 Cooperative Family Registry Breast Cancer Study8 Interdisciplinary Health Research International Team on Breast Cancer Susceptibility8, Teresa M. U. Wagner7, Peter Devilee6, Jacques Simard5, Laura J. van ‘t Veer3, David E. Goldgar1 and Hanne Meijers-Heijboer2

1 International Agency for Research on Cancer, Lyon, France; 2 Erasmus University Medical Center, Rotterdam, the Netherlands; 3 The Netherlands Cancer Institute, Amsterdam, the Netherlands; 4 Stanford Genome Technology Center, Palo Alto, California; 5 Centre Hospitalier de l’Universite de Laval-Centre Hospitalier de l’Université de Québec, Sainte-Foy, Quebec, Canada; 6 Leiden University Medical Center, Leiden, the Netherlands; and 7 University of Vienna, Vienna, Austria

Two mutations of the ATM gene were recently suggested to confer breast cancer risks similar to mutations of BRCA1 or BRCA2. Here, we set out to confirm these findings in 961 families with non-BRCA1/BRCA2 breast cancer from diverse geographical regions. We did not detect the ATM 7271T->G mutation in any family. The ATM IVS10–6T->G mutation was detected in eight families, which was similar to its frequency among population-matched control individuals (pooled Mantel-Haenszel odds ratio = 1.60; 95% confidence interval = 0.48 to 5.35; P = 0.44). Bayesian analysis of linkage in the ATM IVS10–6T->G-positive families showed an overall posterior probability of causality for this mutation of 0.008. We conclude that the ATM IVS10–6T->G mutation does not confer a significantly elevated breast cancer risk and that ATM 7271T->G is a rare event in familial breast cancer.




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