BRCA1/2 and CHEK2 mutation prevalence in patients with breast and/or ovarian cancer in the South of Russia.

Abstract

e13088 Background: The development of breast cancer (BC) and ovarian cancer (OC), as well as their chemoresistance may be due to the presence of mutations in many genes, but most often in BRCA1/2 and CHEK2. Early diagnosis and subsequent preventive interventions improve the survival of patients with mutations in the BRCA1/2 genes. Genotyping of the gene inactivation events predicts a high sensitivity of BC and OC to platinum-containing cytostatics. Our purpose was to study the spectrum of germline mutations in the BRCA1/2 and CHEK2 genes in BC and/or OC patients in the South of Russia. Methods: The study included 622 patients of 10 nationalities with BC and/or OC from the South of Russia. Genomic DNA was isolated from peripheral blood leukocytes; mutations were detected by Real-Time PCR in the BRCA1 (185delAG, 300T > C, 2080delA, 4154delA, 5382insC, 3819delGTAAA, 3875delGTCT), BRCA2 (6174delT), CHEK2 (1100delC, IVS2+1G > A, 470T > C) genes. Results: Mutations in the BRCA1/2 gene were found in 13.5% of cases, in CHEK2 – 6.2%. In the BRCA1/2 gene, the frequency of 5382insC mutation was 76.2%; 4153 delA – 9.5%; 300T > G – 7.1%; 2080delA – 3.6%; 185delAG, 3875delGTCT, 6174delT - 1.2% each. In the CHEK2 gene: 470Т > C – 73.1%; IVS2+1G > A – 23.1%; 1100delC – 3.8%. Two patients showed a combination of 5382insC mutation in the BRCA1 gene and 470T > C mutation in the CHEK2 gene. The observed prevalence of mutations in BRCA1 was generally consistent with that for European countries (p = 0.062). Identification of 470T > C mutation in CHEK2 in two cases confirmed the final diagnosis of Li-Fraumeni syndrome (OMIM: 609265); however, we failed to establish a family history of cancer in one patient. A high-risk cancer group was formed for prophylactic purposes based on the data of genotyping for major mutations in the BRCA1/2 and CHEK2 genes in patients with BC/OC and their healthy relatives. Conclusions: The frequency of BRCA1/2 and CHEK2 mutations in the studied multinational population of Caucasian patients with BC and/or OC was 17.2%. The 5382insC BRCA1/2 (76.2%) and 470Т > C CHEK2 (73.1%) mutations were the most frequent which corresponded to the occurrence of these SNPs in populations of European countries.