GERMINATIVE MUTATIONS LANDSCAPE IN MINAS GERAIS, BRAZIL PATIENTS UNDERGONE TO GENETIC COUNSELING FOR GYNECOLOGICAL AND BREAST CANCER

Most gynecological cancers are sporadic, but approximately 5 % of endometrial cancer (EC), 25% of ovarian cancer (OC) and 10-30% of breast cancer (BC) have hereditary pattern. Hereditary tumor-associated syndromes such as Lynch syndrome (LS), Li-Fraumeni syndrome (LFS), Peutz-Jeghers syndrome (PJS), and Cowden syndrome (CS) also represent an important feature in the carcinogenesis of gynecological and breast tumors. The understanding of genetic predisposition to cancer leads to better identification of patients at risk thus physicians will be able to coordinate strategies for detection, management, and preventive measures against the disease. The aim of this study was to evaluate the profile of germline mutations in patients from different regions of Minas Gerais State, who were submitted to genetic counseling for risk assessment for BC, OC, and EC with possible hereditary pattern. Medical records of 382 patients who underwent genetic counseling after informed consent were analyzed. For the composition of the sample, the following variables were analyzed: age, sex, place of birth, personal or family history of BC, OC, EC and other types of cancer associated with hereditary syndromes. Epidemiological data were analyzed using appropriate statistical tools. The Human Genome Variation Society (HGVS) nomenclature guidelines were used to name the identified variants and the biological significance of all related variants were determined by comparing 11 different databases. We identified 53 distinct mutations: 29 pathogenic variants, 13 variants of undetermined significance (VUS) and 11 benign. The most frequent mutations were BRCA1 c.470_471delCT, BRCA1 c.4675+1G>T and BRCA2 c.2T> G. 21 variants appear to have been described for the first time in Brazil. In addition to BRCA1/2 mutations, variants in other genes related to hereditary syndromes that predispose to gynecological cancers were found. This study allowed a deeper understanding of the main mutations identified in families in the state of Minas Gerais and demonstrates the need to assess family history of non-gynecological cancer for risk assessment of BC, OC, and EC. Moreover, it is an effort that contributes to population studies to evaluate Brazilian’s risk cancer mutation profile.