A1 Refereed original research article in a scientific journal
Recurrent moderate-risk mutations in Finnish breast and ovarian cancer patients
Authors: Anna Nurmi, Taru A. Muranen, Liisa M. Pelttari, Johanna I. Kiiski, Tuomas Heikkinen, Sini Lehto, Anne Kallioniemi, Johanna Schleutker, Ralf Bützow, Carl Blomqvist, Kristiina Aittomäki, Heli Nevanlinna
Publisher: Wiley-Liss Inc.
Publication year: 2019
Journal: International Journal of Cancer
Journal name in source: International Journal of Cancer
Volume: 145
Issue: 10
First page : 2692
Last page: 2700
Number of pages: 9
ISSN: 0020-7136
eISSN: 1097-0215
DOI: https://doi.org/10.1002/ijc.32309
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/40230016
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.
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