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Recurrent moderate-risk mutations in Finnish breast and ovarian cancer patients.

  • Nurmi, Anna1
  • Muranen, Taru A1
  • Pelttari, Liisa M1
  • Kiiski, Johanna I1
  • Heikkinen, Tuomas1
  • Lehto, Sini1
  • Kallioniemi, Anne2
  • Schleutker, Johanna3
  • Bützow, Ralf1, 4
  • Blomqvist, Carl5
  • Aittomäki, Kristiina6
  • Nevanlinna, Heli1
  • 1 Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. , (Finland)
  • 2 BioMediTech Institute and Faculty of Medicine and Health Technology, Tampere University and Fimlab Laboratories, Tampere, Finland. , (Finland)
  • 3 Institute of Biomedicine, University of Turku, and Department of Medical Genetics, Genomics, Laboratory Division, Turku University Hospital, Turku, Finland. , (Finland)
  • 4 Department of Pathology and University of Helsinki and Helsinki University Hospital, Helsinki, Finland. , (Finland)
  • 5 Department of Oncology and University of Helsinki and Helsinki University Hospital, Helsinki, Finland. , (Finland)
  • 6 Department of Clinical Genetics, University of Helsinki, and HUSLAB, Helsinki University Hospital, Helsinki, Finland. , (Finland)
Published Article
International Journal of Cancer
Wiley (John Wiley & Sons)
Publication Date
Nov 15, 2019
DOI: 10.1002/ijc.32309
PMID: 30927251


Mutations in BRCA1 and BRCA2 genes predispose to breast and ovarian cancer (BC/OC) with a high lifetime risk, whereas mutations in PALB2, CHEK2, ATM, FANCM, RAD51C and RAD51D genes cause a moderately elevated risk. In the Finnish population, recurrent mutations have been identified in all of these genes, the latest being CHEK2 c.319+2T>A and c.444+1G>A. By genotyping 3,156 cases and 2,089 controls, we estimated the frequencies of CHEK2 c.319+2T>A and c.444+1G>A in Finnish BC patients. CHEK2 c.319+2T>A was detected in 0.7% of the patients, and it was associated with a high risk of BC in the unselected patient group (OR = 5.40 [95% CI 1.58-18.45], p = 0.007) and similarly in the familial patient group. CHEK2 c.444+1G>A was identified in 0.1% of all patients. Additionally, we evaluated the combined prevalence of recurrent moderate-risk gene mutations in 2,487 BC patients, 556 OC patients and 261 BRCA1/2 carriers from 109 families. The overall frequency of the mutations was 13.3% in 1,141 BRCA1/2-negative familial BC patients, 7.5% in 1,727 unselected BC patients and 7.2% in 556 unselected OC patients. At least one moderate-risk gene mutation was found in 12.5% of BRCA1 families and 7.1% of BRCA1 index patients, as well as in 17.0% of BRCA2 families and 11.3% of BRCA2 index patients, and the mutations were associated with an additional risk in the BRCA1/2 index patients (OR = 2.63 [1.15-5.48], p = 0.011). These results support gene panel testing of even multiple members of BC families where several mutations may segregate in different individuals. © 2019 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.

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