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Evaluation of variants in the CHEK2, BRIP1 and PALB2 genes in an Irish breast cancer cohort

  • Epidemiology
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An Erratum to this article was published on 29 March 2011

Abstract

It has been proposed that rare variants within the double strand break repair genes CHEK2, BRIP1 and PALB2 predispose to breast cancer. The aim of this study was to evaluate the prevalence of these variants in an Irish breast cancer cohort and determine their contribution to the development of breast cancer in the west of Ireland. We evaluated the presence of CHEK2_1100delC variant in 903 breast cancer cases and 1,016 controls. Six previously described variants within BRIP1 and five within PALB2 were screened in 192 patients with early-onset or familial breast cancer. Where a variant was evident, it was then examined in the remainder of our 711 unselected breast cancer cases. CHEK2_1100delC was found in 5/903 (0.5%) breast cancer cases compared to 1/1016 (0.1%) controls. One mutation at BRIP1 (2392 C>T) was identified in the early-onset/familial cohort. Examination of this variant in the remainder of our cohort (711 cases) failed to identify any additional cases. None of the previously described PALB2 variants were demonstrated in the early-onset/familial cohort. We show evidence of CHEK2_1100delC and BRIP1 2392 C>T within the Irish population. CHEK2_1100delC and BRIP1 mutations incidence in Ireland is similar to that found in other unselected breast cancer cohorts from northern European countries. We found no evidence to suggest that PALB2 mutation is an important breast cancer predisposition gene in this population.

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Acknowledgments

We are grateful to the patients in the study and colleagues involved in patient ascertainment and sample collection. Help was also kindly provided by the Equipment Park, London Research Institute, Cancer Research UK. NM and GC were funded by the National Breast Cancer Research Institute, Ireland. ES was funded by a Department of Health Clinician Award and via the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre award to Guy’s & St. Thomas’ NHS Foundation Trust in partnership with King’s College London and King’s College Hospital NHS Foundation Trust.

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Authors and Affiliations

  1. Department of Surgery, Clinical Science Institute, University College Hospital, Galway, Ireland

    N. M. McInerney, N. Miller, G. Colleran, C. Curran & M. J. Kerin

  2. Molecular and Population Genetics Laboratory, Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford, OX3 7BN, UK

    N. M. McInerney, A. Rowan, G. Colleran, E. Barclay, I. P. Tomlinson & E. Sawyer

  3. Guy’s, King’s, St. Thomas’ Cancer Centre, Guy’s Hospital, St. Thomas’s Street, London, SE1 9RT, UK

    E. Sawyer

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  1. N. M. McInerney
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Correspondence to N. M. McInerney.

Additional information

An erratum to this article can be found at http://dx.doi.org/10.1007/s10549-011-1464-8

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McInerney, N.M., Miller, N., Rowan, A. et al. Evaluation of variants in the CHEK2, BRIP1 and PALB2 genes in an Irish breast cancer cohort. Breast Cancer Res Treat 121, 203–210 (2010). https://doi.org/10.1007/s10549-009-0540-9

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