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Review
. 2022 Sep;8(9):759-770.
doi: 10.1016/j.trecan.2022.04.009. Epub 2022 May 25.

CHEK2 variants: linking functional impact to cancer risk

Rick A C M Boonen  1 , Maaike P G Vreeswijk  1 , Haico van Attikum  2
Affiliations
Free article
Review

CHEK2 variants: linking functional impact to cancer risk

Rick A C M Boonen et al. Trends Cancer. 2022 Sep.
Free article

Abstract

Protein-truncating variants in the breast cancer susceptibility gene CHEK2 are associated with a moderately increased risk of breast cancer. By contrast, for missense variants of uncertain significance (VUS) in CHEK2 the associated breast cancer risk is often unclear. To facilitate their classification, functional assays that determine the impact of missense VUS on CHK2 protein function have been performed. Here we discuss these functional analyses that consistently reveal an association between impaired protein function and increased breast cancer risk. Overall, these findings suggest that damaging CHEK2 missense VUS are associated with a risk of breast cancer similar to that of protein-truncating variants. This indicates the urgency of expanding the functional characterization of CHEK2 missense VUS to further understand the associated cancer risk.

Keywords: CHEK2; VUS; breast cancer; cancer risk; functional assay; variant classification; variant of uncertain significance.

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Conflict of interest statement

Declaration of interests The authors declare no conflicts of interest.

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