Familial history and prevalence of BRCA1, BRCA2 and TP53 pathogenic variants in HBOC Brazilian patients from a public healthcare service
| Autor: | Bruna Palma Matta, Renan Gomes, Daniel Mattos, Renata Olicio, Caroline Macedo Nascimento, Gerson Moura Ferreira, Ayslan Castro Brant, Mariana Boroni, Carolina Furtado, Valdirene Lima, Miguel Ângelo Martins Moreira, Anna Cláudia Evangelista dos Santos |
|---|---|
| Přispěvatelé: | Institut Català de la Salut, [Matta BP, Mattos D, Olicio R] Programa de Genética e Virologia Tumoral, Instituto Nacional de Câncer (INCA), Rio de Janeiro, Brazil. [Gomes R] Programa de Genética e Virologia Tumoral, Instituto Nacional de Câncer (INCA), Rio de Janeiro, Brazil. Hereditary Cancer Genetics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Macedo do Nascimento C] Programa de Genética e Virologia Tumoral, Instituto Nacional de Câncer (INCA), Rio de Janeiro, Brazil. Programa de Pós Graduação em Genética, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil. [Moura Ferreira G] Centro de Transplante de Medula Óssea, Instituto Nacional de Câncer (INCA), Rio de Janeiro, Brazil, Vall d'Hebron Barcelona Hospital Campus |
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Neoplasms::Neoplasms by Site::Breast Neoplasms [DISEASES]
Genetic Phenomena::Genotype::Genetic Predisposition to Disease [PHENOMENA AND PROCESSES] Diàtesi Breast Neoplasms Ovaris - Càncer - Aspectes genètics Carcinoma Ovarian Epithelial neoplasias::neoplasias por localización::neoplasias de las glándulas endocrinas::neoplasias ováricas [ENFERMEDADES] Neoplastic Syndromes Hereditary Prevalence Humans Genetic Predisposition to Disease Germ-Line Mutation fenómenos genéticos::genotipo::predisposición genética a la enfermedad [FENÓMENOS Y PROCESOS] Ovarian Neoplasms BRCA2 Protein neoplasias::neoplasias por localización::neoplasias de la mama [ENFERMEDADES] Multidisciplinary BRCA1 Protein Neoplasms::Neoplasms by Site::Endocrine Gland Neoplasms::Ovarian Neoplasms [DISEASES] técnicas de investigación::métodos epidemiológicos::recopilación de datos::estadísticas vitales::morbilidad::prevalencia [TÉCNICAS Y EQUIPOS ANALÍTICOS DIAGNÓSTICOS Y TERAPÉUTICOS] Investigative Techniques::Epidemiologic Methods::Data Collection::Vital Statistics::Morbidity::Prevalence [ANALYTICAL DIAGNOSTIC AND THERAPEUTIC TECHNIQUES AND EQUIPMENT] Mama - Càncer - Aspectes genètics Female Tumor Suppressor Protein p53 Delivery of Health Care Brazil |
| Zdroj: | Scientia |
| Popis: | Cancer; Genetics; Risk factors Cáncer; Genética; Factores de riesgo Càncer; Genètica; Factors de risc Several studies have demonstrated the cost-effectiveness of genetic testing for surveillance and treatment of carriers of germline pathogenic variants associated with hereditary breast/ovarian cancer syndrome (HBOC). In Brazil, seventy percent of the population is assisted by the public Unified Health System (SUS), where genetic testing is still unavailable. And few studies were performed regarding the prevalence of HBOC pathogenic variants in this context. Here, we estimated the prevalence of germline pathogenic variants in BRCA1, BRCA2 and TP53 genes in Brazilian patients suspected of HBOC and referred to public healthcare service. Predictive power of risk prediction models for detecting mutation carriers was also evaluated. We found that 41 out of 257 tested patients (15.9%) were carriers of pathogenic variants in the analyzed genes. Most frequent pathogenic variant was the founder Brazilian mutation TP53 c.1010G > A (p.Arg337His), adding to the accumulated evidence that supports inclusion of TP53 in routine testing of Brazilian HBOC patients. Surprisingly, BRCA1 c.5266dupC (p.Gln1756fs), a frequently reported pathogenic variant in Brazilian HBOC patients, was not observed. Regarding the use of predictive models, we found that familial history of cancer might be used to improve selection or prioritization of patients for genetic testing, especially in a context of limited resources. We are very thankful to all patients and their families who participated in this study. We thank Eliana Abdelhay for providing the Ion AmpliSeq customized panel and funding the sequencing costs for this panel. And we also thank the Bioinformatics Core Facility (INCA-RJ), in special Dr. Nicole Scherer, for their support in this study. This work was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, Brazil: project 304339/2018-0), Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ, Brazil: projects 200.928/2021 and 211.309/2021), Fundação Ary Frauzino para Pesquisa e Controle do Câncer (Brazil), SWISS-BRIDGE Foundation, and Ministry of Health (Brazil). |
| Databáze: | OpenAIRE |
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