A1 Refereed original research article in a scientific journal

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




AuthorsAnna 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

PublisherWiley-Liss Inc.

Publication year2019

JournalInternational Journal of Cancer

Journal name in sourceInternational Journal of Cancer

Volume145

Issue10

First page 2692

Last page2700

Number of pages9

ISSN0020-7136

eISSN1097-0215

DOIhttps://doi.org/10.1002/ijc.32309

Self-archived copy’s web addresshttps://research.utu.fi/converis/portal/detail/Publication/40230016


Abstract

Mutations in BRCA1 and BRCA2 genes predispose to breast and ovarian cancer (BC/OC) with a high lifetime risk, whereas mutations in PALB2CHEK2ATMFANCMRAD51C 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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