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A Finnish founder mutation in RAD51D: analysis in breast, ovarian, prostate, and colorectal cancer
  1. Liisa M Pelttari1,
  2. Johanna Kiiski1,
  3. Riikka Nurminen2,
  4. Anne Kallioniemi2,
  5. Johanna Schleutker2,3,
  6. Alexandra Gylfe4,
  7. Lauri A Aaltonen4,
  8. Arto Leminen1,
  9. Päivi Heikkilä5,
  10. Carl Blomqvist6,
  11. Ralf Bützow1,5,
  12. Kristiina Aittomäki4,7,
  13. Heli Nevanlinna1
  1. 1Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland
  2. 2Institute of Biomedical Technology/BioMediTech, University of Tampere and Fimlab Laboratories, Tampere, Finland
  3. 3Department of Medical Biochemistry and Genetics, University of Turku, Turku, Finland
  4. 4Department of Medical Genetics, Genome-Scale Biology Research Program, University of Helsinki, Helsinki, Finland
  5. 5Department of Pathology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland
  6. 6Department of Oncology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland
  7. 7Department of Clinical Genetics, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland
  1. Correspondence to Dr Heli Nevanlinna, Helsinki University Central Hospital, Department of Obstetrics and Gynecology, Biomedicum Helsinki, PO Box 700, FIN-00029 HUS, Finland; heli.nevanlinna{at}


Background RAD51D and RAD54L are involved in homologous recombination, and rare mutations in RAD51D were recently found in breast-ovarian cancer families. This study investigated RAD51D and RAD54L for mutations in breast and ovarian cancer patients in the Finnish population.

Methods The study sequenced the RAD51D and RAD54L genes in 95 breast and/or ovarian cancer families and genotyped the identified mutation in an additional 2200 breast and 553 ovarian cancer patients and 2102 population controls. To investigate the role of the mutation in other common cancers, 1094 prostate and 980 colorectal cancer patients were genotyped.

Results In the screening of RAD51D, one deleterious founder mutation c.576+1G>A was identified in two breast-ovarian cancer families. No mutations were found in RAD54L. Altogether, the c.576+1G>A mutation was detected in 5/707 patients with a personal or family history of ovarian cancer (OR 9.16, 95% CI 1.07 to 78.56; p=0.024), with the highest frequency among breast-ovarian cancer families (3/105 vs 1/1287 controls, OR 37.82, 95% CI 3.90 to 366.91; p=0.0016), but no elevated frequency among breast cancer patients/families (2/2105, p=1). The mutation was not found among prostate or colorectal cancer patients.

Conclusions The results of this study on familial and unselected breast, ovarian, colorectal, and prostate cancer patients suggest that RAD51D is primarily a moderate penetrance susceptibility gene for ovarian cancer, with clinical significance for the carriers.

  • RAD51D
  • ovarian cancer
  • breast cancer
  • founder mutation
  • genetics, cancer: prostate
  • molecular genetics
  • genetic epidemiology
  • genome-wide
  • diagnostics

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  • Funding This work was supported by the Helsinki University Central Hospital Research Fund, the Academy of Finland (132473), the Sigrid Juselius Foundation, and the Finnish Cancer Society.

  • Competing interests None.

  • Ethics approval Helsinki University Central Hospital Ethic Committee.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement No additional data available.