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A nonsense mutation (E1978X) in the ATM gene is associated with breast cancer

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Abstract

Blood relatives of patients with ataxia-telangiectasia (A-T) have an increased risk to develop breast cancer. Allelic heterogeneity has made it difficult to confirm the role of ATM, the gene mutated in A-T, for breast cancer susceptibility in the general population. We now report that a nonsense mutation, p.E1978X (c.5932G>T), is both a classical A-T mutation and a breast cancer susceptibility allele in Eastern European populations. In a case–control study from Belarus, the E1978X mutation was identified in 10/1,891 Byelorussian breast cancer cases (0.5%) compared with 1/1,019 population controls [odds ratio (OR): 5.4; 95% confidence interval (95% CI), 0.7–42.4, P = 0.1]. A second case–control study from Russia identified the E1978X mutation in two Russian and one Ukrainian cases out of 611 breast cancer patients but not in any Russian or Ukrainian controls (P = 0.1). In a third case–control study from Poland, E1978X was observed in 7/3,910 Polish breast cancer cases (0.2%) compared with 1/2,010 cancer-free population controls (OR: 3.6; 95% CI: 0.4–29.3, P = 0.4). In the combined analysis, E1978X was significantly associated with breast cancer (Mantel–Haenszel OR: 5.6, 95% CI: 1.3–21.4, P = 0.01). Taken together, this study provides first evidence for the association of a common A-T causing mutation with breast cancer in Eastern European founder populations.

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Acknowledgments

We cordially thank all patients and control individuals who took part in this study. We gratefully acknowledge Professor Johann H. Karstens for his continuous support of our breast cancer studies at Hannover Medical School. We furthermore thank Dominika Wokolorczyk for excellent technical assistance. We keep in grateful memory our colleague Dr. Sergei Feshchenko whose cooperation was seminal to establish the Hannover–Minsk breast cancer study. M.B. and T.D. received financial support from the International Bureau of the German Ministry of Research and Education (RUS08/017). N·B. and I.D. have been fellows of the German Academic Exchange Program, and N·B. was generously supported by the Friends of Hannover Medical School.

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Authors and Affiliations

  1. Department of Obstetrics and Gynaecology, Hannover Medical School, Carl-Neuberg-St. 1, 30625, Hannover, Germany

    Natalia Bogdanova, Paria Yamini, Peter Hillemanns & Thilo Dörk

  2. Clinics of Radiation Oncology, Hannover Medical School, Hannover, Germany

    Natalia Bogdanova & Paria Yamini

  3. Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland

    Cezary Cybulski & Jan Lubinski

  4. Institute of Biochemistry and Genetics, Ufa Scientific Center of Russian Academy of Sciences, Ufa, Russia

    Marina Bermisheva & Elza Khusnutdinova

  5. R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, National Academy of Sciences, Kyiv, Ukraine

    Ihor Datsyuk

  6. N.N. Alexandrov Research Institute of Oncology and Medical Radiology, Minsk, Belarus

    Natalja Nikolaevna Antonenkova

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  1. Natalia Bogdanova
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  2. Cezary Cybulski
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  3. Marina Bermisheva
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  7. Natalja Nikolaevna Antonenkova
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  9. Jan Lubinski
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  10. Thilo Dörk
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Correspondence to Thilo Dörk.

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Bogdanova, N., Cybulski, C., Bermisheva, M. et al. A nonsense mutation (E1978X) in the ATM gene is associated with breast cancer. Breast Cancer Res Treat 118, 207–211 (2009). https://doi.org/10.1007/s10549-008-0189-9

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  • DOI: https://doi.org/10.1007/s10549-008-0189-9

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