17CHEK2 gene mutations in breast cancer patients with BRCA1/2 positive or negative status

Background: The principal hereditary breast cancer susceptibility genes are BRCA1 and BRCA2, while the impact of other genes have been discovered as well. CHEK2 is a tumour suppressor gene of DNA repair that correlate with an increased risk for breast cancer. This risk is traditionally higher for families with hereditary burden of breast cancer. The prevalence of CHEK2 mutations among women with family history and different BRCA 1/2 status is unknown. We aimed to analyse additional CHEK2 mutations in breast cancer patients with high-risk family history depending of BRCA 1/2 status. Methods: Peripheral blood of 122 women with breast cancer were tested for progenitor mutations in BRCA1/2 (185delAG, 5382insC, T300G, 6174delT) genes and mutations in CHEK2 (1100delC, IVS2 + 1>A, I157T) gene using PCR and PCR-RLFP. Results: Overall, 120 women were included, 18 (15%) were BRCA1 positive (5382insC mutations) and 102 (85%) BRCA1/2 negative (no tested mutations). Median age was 42 years in BRCA1 positive and 46 years in BRCA1/2 negative groups. CHEK2 mutations were defined in 9 (7,5%) cases (IVS2 + 1G>A, n = 2; I157T, n = 7) that were associated with a history of breast cancer in a first- and second-degree relatives. CHEK2 mutations (IVS2 + 1G>A and I157T) were found in 2 and 6 cases, respectively, in BRCA1/2 negative group. Patients from BRCA1 positive group had one case of CHEK2 (I157T) mutation. 1100delC mutation in CHEK2 gene was not detected in these patients. We found no difference in prevalence of CHEK2 mutations in groups depending BRCA1/2 status (7,8% and 5,5%, respectively), except for clinical features (less aggressive course). Conclusions: In summary, our results showed the IVS2 + 1G>A and I157T CHEK2 mutations prevalence found among women with family history breast cancer was 7,5% (9/120). Moreover, we identified the association between I157T CHEK2 and 5382insC BRCA1 mutations with one case of hereditary breast cancer. Obtained results suggest that IVS2 + 1G>A and I157T CHEK2 mutations could potentially contribute to the susceptibility to breast cancer and might combined with BRCA1 progenitor mutation influencing on clinical features. Large case-control studies are needed to establish the significance of CHEK2 mutations among Ukrainian breast cancer patients for clinical implications understanding. Legal entity responsible for the study: Department of Oncology, Bogomolets National Medical University, Ukraine. Funding: Ministry of Health of Ukraine Disclosure: All authors have declared no conflicts of interest.