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BRCA1/BRCA2 founder mutations and cancer risks: impact in the western Danish population

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Abstract

Mutations in the BRCA1 and BRCA2 genes significantly contribute to hereditary breast cancer and ovarian cancer, but the phenotypic effect from different mutations is insufficiently recognized. We used a western Danish clinic-based cohort of 299 BRCA families to study the female cancer risk in mutation carriers and their untested first-degree relatives. Founder mutations were characterized and the risk of cancer was assessed in relation to the specific mutations. In BRCA1, the cumulative cancer risk at age 70 was 35 % for breast cancer and 29 % for ovarian cancer. In BRCA2, the cumulative risk was 44 % for breast cancer and 15 % for ovarian cancer. We identified 47 distinct BRCA1 mutations and 48 distinct mutations in BRCA2. Among these, 8 founder mutations [BRCA1 c.81-?_4986+?del, c.3319G>T (p.Glu1107*), c.3874delT and c.5213G>A (p.Gly1738Glu) and BRCA2 c.6373delA, c.7008−1G>A, c.7617+1G>A and c.8474delC] were found to account for 23 % of the BRCA1 mutations and for 32 % of the BRCA2 mutations. The BRCA1 mutation c.3319G>T was, compared to other BRCA1 mutations, associated with a higher risk for ovarian cancer. In conclusion, founder mutations in BRCA1 and BRCA2 contribute to up to one-third of the families in western Denmark and among these the BRCA1 c.3319G>T mutation is potentially linked to an increased risk of ovarian cancer.

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Acknowledgments

The study was financially supported by Aase and Ejnar Danielsen’s Fund, The Research Council of Region of Southern Denmark and the Research Council, Vejle Hospital. We would like to acknowledge Clinical Professor Stig E Bojesen, Institute of Clinical Medicine, Herlev Hospital for data on genetic tests.

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Authors and Affiliations

  1. Department of Clinical Genetics, Vejle Hospital, Vejle, Denmark

    Henriette Roed Nielsen

  2. HNPCC Register, Clinical Research Center, Copenhagen University Hospital, Hvidovre, Denmark

    Mef Nilbert, Janne Petersen, Steen Ladelund & Christina Therkildsen

  3. Section of Biostatistics, Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

    Janne Petersen

  4. Department of Biochemistry, Pharmacology and Genetics, Odense University Hospital, Odense, Denmark

    Mads Thomassen

  5. Section of Molecular Diagnostics, Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark

    Inge Søkilde Pedersen

  6. Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark

    Thomas V. O. Hansen

  7. Department of Clinical Genetics, Aarhus University Hospital, Aarhus, Denmark

    Anne-Bine Skytte

  8. Institute of Clinical Sciences, Department of Oncology and Pathology, Lund University, Lund, Sweden

    Åke Borg

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  1. Henriette Roed Nielsen
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Correspondence to Christina Therkildsen.

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Nielsen, H.R., Nilbert, M., Petersen, J. et al. BRCA1/BRCA2 founder mutations and cancer risks: impact in the western Danish population. Familial Cancer 15, 507–512 (2016). https://doi.org/10.1007/s10689-016-9875-7

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  • DOI: https://doi.org/10.1007/s10689-016-9875-7

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