Perfil de mutações germinativas em pacientes submetidas a aconselhamento genético para câncer hereditário de mama, ovário e endométrio, em Minas Gerais, Brasil

• Ano de defesa: 2020
• Autor(a) principal: Camila Martins de Carvalho
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Minas Gerais; Brasil; MED - DEPARTAMENTO DE GINECOLOGIA OBSTETRÍCIA; Programa de Pós-Graduação em Saúde da Mulher; UFMG
• Palavras-chave em Português: Neoplasia ovariana; Neoplasia de mama; Neoplasia de endométrio; Síndromes neoplásicas hereditárias; Neoplasias Ovarianas; Neoplasias da Mama; Neoplasias do Endométrio; Estudos Retrospectivos; Mutação em Linhagem Germinativa; Aconselhamento Genético; Síndromes Neoplásicas Hereditárias; Dissertação Acadêmica
• Link de acesso: http://hdl.handle.net/1843/37472

Most gynecological cancers are sporadic, but about 5 to 10% of cases have a hereditary pattern. Most cases of hereditary breast cancer (BC) and ovarian cancer (OC) are attributable to mutations in one of the BRCA genes. The risk of gynecological malignancies may be associated, less frequently, with other hereditary cancer predisposing syndromes, such as Li-Fraumeni Syndrome, Lynch Syndrome, and Cowden Syndrome. Understanding the genetic predisposition to cancer leads to better identification of patients at risk thus gynecologists, mastologists, oncologists and geneticists will be able to coordinate strategies for detection, management, and preventive measures against the disease. This was a retrospective study that evaluated the profile of germline mutations present in patients who underwent genetic counseling for risk assessment for BC, OC, and endometrial cancer (EC) with a possible hereditary pattern, in Minas Gerais, Brazil. Medical records of 382 patients from different regions of the state were analyzed for the following variables: 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 ClinVar and BRCA Exchange databases were used to determine the biological significance of all related variants. We identified 53 distinct mutations: 29 were 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. 25 variants appear to have been described for the first time in Brazil, of which 3 were never described in ClinVar. In addition to BRCA1/2 mutations, variants in other genes related to hereditary syndromes that predispose to gynecological cancers were found. These results were described as a scientific article for publication in Scientific Reports, since 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 for population studies to evaluate the mutation profile in the Brazilian population.