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Analysis of the genes coding for the BRCA1-interacting proteins, RAP80 and Abraxas (CCDC98), in high-risk, non-BRCA1/2, multiethnic breast cancer cases

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Abstract

Background Around half of familial breast cancer cases are caused by germ-line mutations in genes which are critically involved in the maintenance of genome stability. Mutations in related genes functioning in DNA repair may account for currently unattributed cases. Two such genes, RAP80 and Abraxas, have recently been identified to be in a complex with BRCA1, and are required for the localization of BRCA1 to DNA damage foci. Methods RAP80 and Abraxas variants were screened for in a cohort of 95 high risk, non-BRCA1/2 breast cancer cases of varying ethnicity: those of Ashkenazi Jewish (n = 35), mixed Canadian (n = 34) and Swiss descent (n = 26). Results We have identified four missense variants, four silent SNPs, three SNPs in the UTRs and seven intronic variants in RAP80. Two of the previously reported RAP80 variants were further investigated. In Abraxas, we have identified two missense, nine intronic and two variants in the 3′ UTR. Conclusions Overall, it seems unlikely that moderate to highly penetrant alleles of either RAP80 or Abraxas, confer a significantly high relative risk of breast cancer.

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Acknowledgements

We would like to thank George Chong and Lili Li for their help with this project. The work was funded by grants from the Canadian Breast Cancer Research Alliance (W.D.F. and T.A.B.), Jewish General Hospital Weekend to End Breast Cancer, Rethink Breast Cancer Canada, the Canadian Foundation for Innovation (M.T.). W.D.F. holds a Fonds de la Recherche en Santé du Québec national scientist award. M.T holds a Fonds de la Recherche en Santé du Québec clinician-scientist award.

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Authors and Affiliations

  1. Departments of Oncology and Human Genetics, Program in Cancer Genetics, McGill University, Montreal, QC, Canada, H2W 1S6

    David J. Novak, Nelly Sabbaghian, William D. Foulkes & Marc Tischkowitz

  2. Departments of Medicine and Human Genetics, McGill University, Montreal, QC, Canada, H2W 1S6

    David J. Novak, William D. Foulkes & Marc Tischkowitz

  3. Segal Cancer Center, McGill University Sir M. B. Davis-Jewish General Hospital, 3755 Cote Ste-Catherine, Montreal, QC, Canada, H3T 1E2

    David J. Novak, Nelly Sabbaghian, William D. Foulkes & Marc Tischkowitz

  4. Laboratory of Molecular Oncology, Division of Laboratory Medicine, Department of Genetic Medicine and Laboratory, University Hospitals of Geneva, 1211, Geneva 14, Switzerland

    Philippe Maillet

  5. Unit of Oncogenetics and Cancer Prevention, Division of Oncology, Department of Internal Medicine; Division of Genetic Medicine, Department of Genetic Medicine and Laboratory, University Hospitals of Geneva, 1211, Geneva 14, Switzerland

    Pierre O. Chappuis

  6. The Research Institute, McGill University Health Centre, Montreal, QC, Canada, H3G 1A4

    William D. Foulkes

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  1. David J. Novak
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  2. Nelly Sabbaghian
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  3. Philippe Maillet
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  4. Pierre O. Chappuis
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  5. William D. Foulkes
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  6. Marc Tischkowitz
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Correspondence to Marc Tischkowitz.

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Novak, D.J., Sabbaghian, N., Maillet, P. et al. Analysis of the genes coding for the BRCA1-interacting proteins, RAP80 and Abraxas (CCDC98), in high-risk, non-BRCA1/2, multiethnic breast cancer cases. Breast Cancer Res Treat 117, 453–459 (2009). https://doi.org/10.1007/s10549-008-0134-y

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  • DOI: https://doi.org/10.1007/s10549-008-0134-y

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