Checking for CHEK2 Hereditary Mutations in Ukrainian Women: Lack of CHECK2 Variants Contribution to Breast Cancer Susceptibility

Abstract Introduction/Objective Although the role of homologous recombination repair (HRR) machinery in breast cancer susceptibility has been clearly established, the range and frequency of HRR gene mutations vary profoundly in different populations. Previously high incidence of CHEK2 (Checkpoint kinase 2) mutations was shown in Eastern Europe, however, there is still limited data on the rate of CHEK2 gene mutations and their clinical implications in the Ukrainian population. The aim of this study was to assess the frequency of CHEK2 mutations and investigate whether CHEK2 variants confer susceptibility to breast cancer in Ukrainian women. Methods/Case Report This was a retrospective case-control study performed on 320 female breast cancer patients and 146 unaffected women (control), aged 42,3±0,51 and 40,3±0,84 respectively, who underwent NGS-testing for germline mutations in multiple genes including CHEK2. Only pathogenic (PV) and likely pathogenic (LPV) variants were considered for further analysis. Results (if a Case Study enter NA) The frequency of CHEK2 mutations did not differ significantly between the observed groups: there were 27 (8,4%) carriers among female breast cancer patients and 15 (10,27%) carriers in unaffected women. To note, the breast cancer patients demonstrated a high rate of CHEK2 co-mutations with BRCA1 (PV, n=3) and BRCA2 (n=2, PV). Within the range of CHEK2 genetic alterations, we reported variant c.470T>C (p.Ile157Thr) found in 22 carriers (52,4%) and deletions of exons 9-10 detected in 7 women (16,7%) as most prevalent in Ukrainian population. The rates of CHEK2 c.470T>C (p.Ile157Thr) variant were comparable among the unaffected women (n=5; 3,4%) and breast cancer group (n=17; 5,3%); exon 9-10 deletions were found in 2 (1,36%) and 5 (1,56%) cases respectively. Less frequent CHEK2 mutations were detected in ≤3 cases per group. In this study we report no contribution of CHEK2 genetic alterations to breast cancer susceptibility (OR=1,24; 95%CI 0,64-2,41; p=0,521) in Ukrainian women. Conclusion The frequency of CHEK2 mutation in Ukrainian women is relatively high as compared to available data on other populations. However, we did not find any contribution of CHEK2 pathogenic/likely pathogenic variants to breast cancer susceptibility.