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Further evidence for the contribution of the RAD51C gene in hereditary breast and ovarian cancer susceptibility

Breast Cancer Research and Treatment volume 130, pages 1003–1010 (2011)Cite this article

Abstract

RAD51C, a RAD51 paralogue involved in homologous recombination, is a recently established Fanconi anemia and breast cancer predisposing factor. In the initial report, RAD51C mutations were shown to confer a high risk for both breast and ovarian tumors, but most of the replication studies published so far have failed to identify any additional susceptibility alleles. Here, we report a full mutation screening of the RAD51C gene in 147 Finnish familial breast cancer cases and in 232 unselected ovarian cancer cases originating from Finland and Sweden. In addition, in order to resolve whether common RAD51C SNPs are risk factors for breast cancer, we genotyped five tagging single nucleotide polymorphisms, rs12946522, rs304270, rs304283, rs17222691, and rs28363312, all located within the gene, from 993 Finnish breast cancer cases and 871 controls for cancer associated variants. Whereas, none of the studied common SNPs associated with breast cancer susceptibility, mutation analysis revealed two clearly pathogenic alterations. RAD51C c.-13_14del27 was observed in one familial breast cancer case and c.774delT in one unselected ovarian cancer case, thus confirming that RAD51C mutations are implicated in breast and ovarian cancer predisposition, although their overall frequency seems to be low. Independent identification of the very recently reported RAD51C c.774delT mutation in yet another patient originating from Sweden suggests that it might be a recurrent mutation in that population and should be studied further. The reliable estimation of the clinical implications of carrying a defective RAD51C allele still requires the identification of additional mutation positive families.

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Acknowledgments

We thank Dr. Aki Mustonen, Dr. Jaakko Ignatius, Dr. Karolina Partheen, nurses Kari Mononen and Outi Kajula for their help in sample and data collection, and Meeri Otsukka for technical assistance and help in patient contacts. Jenni Nikkilä and Szilivia Solyom are acknowledged for their technical assistance. This study was financially supported by (RW) the Finnish Cancer Foundation, the Sigrid Jusélius Foundation, the Academy of Finland, the University of Oulu, and the Oulu University Hospital; (KS) the Swedish Cancer Foundation, the King Gustav V Jubilée Clinic Cancer Research Foundation and the Gothenburg Medical Society; (AL) the Swedish Cancer Society.

Conflict of interest statement

None.

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Affiliations

  1. Laboratory of Cancer Genetics, Department of Clinical Genetics and Biocenter Oulu, University of Oulu, Oulu University Hospital, P.O. Box 5000, 90014, Oulu, Finland

    Mikko Vuorela, Katri Pylkäs, Maria Haanpää & Robert Winqvist

  2. Department of Pathology and Forensic Medicine, School of Medicine, Institute of Clinical Medicine, University of Eastern Finland, 70211, Kuopio, Finland

    Jaana M. Hartikainen, Veli-Matti Kosma & Arto Mannermaa

  3. Department of Clinical Pathology, Kuopio University Hospital, 70211, Kuopio, Finland

    Jaana M. Hartikainen, Veli-Matti Kosma & Arto Mannermaa

  4. Department of Obstetrics and Gynecology, Institute of Clinical Sciences, Sahlgrenska Academy at Gothenburg University, Gothenburg, Sweden

    Karin Sundfeldt

  5. Department of Molecular Medicine and Surgery, Karolinska Institutet, 171 76, Stockholm, Sweden

    Annika Lindblom

  6. Department of Oncology-Pathology, Karolinska University Hospital, Karolinska Institutet, 171 76, Stockholm, Sweden

    Anna von Wachenfeldt Wäppling

  7. Department of Obstetrics and Gynecology, University of Oulu, Oulu University Hospital, P.O. Box 5000, 90014, Oulu, Finland

    Ulla Puistola

  8. Intergene Biobank, Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

    Annika Rosengren

  9. Department of Obstetrics and Gynecology, University of Eastern Finland, Kuopio University Hospital, 70211, Kuopio, Finland

    Maarit Anttila

Authors
  1. Mikko Vuorela
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  2. Katri Pylkäs
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  3. Jaana M. Hartikainen
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  4. Karin Sundfeldt
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  5. Annika Lindblom
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  6. Anna von Wachenfeldt Wäppling
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  7. Maria Haanpää
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  8. Ulla Puistola
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  9. Annika Rosengren
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  10. Maarit Anttila
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  11. Veli-Matti Kosma
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  12. Arto Mannermaa
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  13. Robert Winqvist
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Corresponding author

Correspondence to Robert Winqvist.

Additional information

Mikko Vuorela and Katri Pylkäs contributed equally to this work.

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Vuorela, M., Pylkäs, K., Hartikainen, J.M. et al. Further evidence for the contribution of the RAD51C gene in hereditary breast and ovarian cancer susceptibility. Breast Cancer Res Treat 130, 1003–1010 (2011). https://doi.org/10.1007/s10549-011-1677-x

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  • DOI: https://doi.org/10.1007/s10549-011-1677-x

Keywords

  • RAD51C
  • Hereditary breast and ovarian cancer susceptibility
  • Germline mutation