[Pathogenic role of CHEK2 variants in Hungarian cancer patients: implications for breast cancer risk and genetic counselling].

Abstract

Aim: Our study assessed the prevalence of CHEK2 gene variants, including low-penetrance variants (lp-CHEK2: p.I157T, p.S428F, p.T476M) and their association with clinicopathological parameters in cancer patients and controls.

Methods: Germline genetic analysis of 1,280 breast and ovarian cancer (BOC), 191 young breast (<33 years, yBr), 568 nonbreast (non-BOC) and 96 endocrine cancer patients was performed using the Illumina TruSight Hereditary Cancer Panel.

Results: CHEK2 disease-causing (pathogenic/likely pathogenic) variants were more frequent in the BOC and yBr groups (2 and 2.6%) compared to non-BOC and endocrine tumour patients (0.5% and 0%, p=0.049). Lp-CHEK2 variants were detected in 4% of all groups and associated with other disease-causing genetic abnormalities more often than pathogenic/likely pathogenic CHEK2 variants (16% vs. 1%, p<0.0001).

Conclusions: Despite their frequent occurrence, lp-CHEK2 variants confer a negligible risk of breast cancer and show no association with other tumour types. Disease-causing CHEK2 variants, however, have implications for the clinical management of breast cancer patients according to current guidelines.