University of Oulu

Kumpula, T.A., Koivuluoma, S., Soikkonen, L. et al. Evaluating the role of CHEK2 p.(Asp438Tyr) allele in inherited breast cancer predisposition. Familial Cancer 22, 291–294 (2023).

Evaluating the role of CHEK2 p.(Asp438Tyr) allele in inherited breast cancer predisposition

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Author: Kumpula, Timo A.1; Koivuluoma, Susanna1; Soikkonen, Leila2;
Organizations: 1Laboratory of Cancer Genetics and Tumor Biology, Cancer and Translational Medicine Research Unit, Biocenter Oulu, Oulu and NordLab Oulu, FI-90014 University of Oulu, Oulu, P.O. Box 5000, Finland
2Department of Clinical Genetics, Medical Research Center Oulu and PEDEGO Research Unit, Oulu University Hospital, University of Oulu, Oulu, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 0.7 MB)
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Language: English
Published: Springer Nature, 2023
Publish Date: 2023-05-31


CHEK2 is a well-established breast cancer susceptibility gene. The most frequent pathogenic CHEK2 variant is 1100delC, a loss-of-function mutation conferring 2-fold risk for breast cancer. This gene also harbors other rare variants encountered in the clinical gene panels for hereditary cancer. One of these is CHEK2 c.1312 G > T, p.(Asp438Tyr) in the kinase domain of the protein, but due to its rarity its clinical significance for breast cancer predisposition has remained unclear. Here, we tested the prevalence of CHEK2 p.(Asp438Tyr) allele showing enrichment in the Northern Finnish population, in a total of 2284 breast cancer patients from this geographical region. Genotyping was performed for DNA samples extracted from peripheral blood using high-resolution melt analysis. Fourteen CHEK2 p.(Asp438Tyr) carriers were identified (14/2284, 0.6%, P = 0.67): two in the cohort of breast cancer cases with the indication of inherited disease susceptibility (2/281, 0.7%, P = 1.00) and twelve in the breast cancer cohort unselected for the family history of disease and age at disease onset (12/2003, 0.6%, P = 0.66). This frequency did not differ from the frequency in the general population (10/1299, 0.8%). No CHEK2 p.(Asp438Tyr) homozygotes were identified. Our results indicate that CHEK2 p.(Asp438Tyr) carriers do not have an increased risk for breast cancer and the classification of the CHEK2 p.(Asp438Tyr) variant can be changed from the variant of uncertain significance (VUS) to likely benign for breast cancer.

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Series: Familial cancer
ISSN: 1389-9600
ISSN-E: 1573-7292
ISSN-L: 1389-9600
Volume: 22
Issue: 3
Pages: 291 - 294
DOI: 10.1007/s10689-023-00327-2
Type of Publication: A1 Journal article – refereed
Field of Science: 3122 Cancers
Funding: This work was supported by the Academy of Finland [307808], the Cancer Foundation of Finland sr and Sigrid Jusélius foundation.
Academy of Finland Grant Number: 307808
Detailed Information: 307808 (Academy of Finland Funding decision)
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