RESUMO
PURPOSE: This study aimed to identify and classify genetic variants in consensus moderate-to-high-risk predisposition genes associated with Hereditary Breast and Ovarian Cancer Syndrome (HBOC), in BRCA1/2-negative patients from Brazil. METHODS: The study comprised 126 index patients who met NCCN clinical criteria and tested negative for all coding exons and intronic flanking regions of BRCA1/2 genes. Multiplex PCR-based assays were designed to cover the complete coding regions and flanking splicing sites of six genes implicated in HBOC. Sequencing was performed on HiSeq2500 Genome Analyzer. RESULTS: Overall, we identified 488 unique variants. We identified five patients (3.97%) that harbored pathogenic or likely pathogenic variants in four genes: ATM (1), CHEK2 (2), PALB2 (1), and TP53 (1). One hundred and thirty variants were classified as variants of uncertain significance (VUS), 10 of which were predicted to disrupt mRNA splicing (seven non-coding variants and three coding variants), while other six missense VUS were classified as probably damaging by prediction algorithms. CONCLUSION: A detailed mutational profile of non-BRCA genes is still being described in Brazil. In this study, we contributed to filling this gap, by providing important data on the diversity of genetic variants in a Brazilian high-risk patient cohort. ATM, CHEK2, PALB2 and TP53 are well established as HBOC predisposition genes, and the identification of deleterious variants in such actionable genes contributes to clinical management of probands and relatives.
Assuntos
Neoplasias da Mama , Síndrome Hereditária de Câncer de Mama e Ovário , Neoplasias Ovarianas , Proteína BRCA1/genética , Proteína BRCA2/genética , Brasil/epidemiologia , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/genética , Consenso , Feminino , Predisposição Genética para Doença , Células Germinativas , Mutação em Linhagem Germinativa , Síndrome Hereditária de Câncer de Mama e Ovário/epidemiologia , Síndrome Hereditária de Câncer de Mama e Ovário/genética , Humanos , Neoplasias Ovarianas/epidemiologia , Neoplasias Ovarianas/genética , PrevalênciaRESUMO
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.
Assuntos
Neoplasias da Mama , Síndromes Neoplásicas Hereditárias , Neoplasias Ovarianas , Feminino , Humanos , Brasil/epidemiologia , Prevalência , Neoplasias Ovarianas/epidemiologia , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/diagnóstico , Predisposição Genética para Doença , Proteína BRCA2/genética , Proteína BRCA1/genética , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/genética , Neoplasias da Mama/diagnóstico , Carcinoma Epitelial do Ovário , Atenção à Saúde , Mutação em Linhagem Germinativa , Proteína Supressora de Tumor p53/genéticaRESUMO
Objetivo: descrever as percepções das enfermeiras residentes em processo de qualificação para a assistência pré-natal acerca das questões de gênero na consulta de enfermagem. Método: estudo qualitativo, realizado com doze enfermeiras em qualificação, na modalidade de residência, nos serviços de atenção pré-natal, no município do Rio de Janeiro. As entrevistas semiestruturadas ocorreram de outubro a novembro de 2016. Aplicou-se a análise de conteúdo temática. Resultados: as normas de gênero relacionam-se com valores e comportamentos tradicionais associados à maternidade e paternidade. As iniquidades advindas dessas normas são vistas como a causa da violência às mulheres e do limitado envolvimento masculino na gestação. Há restrições de uma perspectiva de gênero nos serviços, apesar de haver homens que buscam uma paternidade mais ativa e casais homoafetivos que recorrem ao atendimento pré-natal. Conclusão: propostas de intervenção com enfoque nessa perspectiva são necessárias na assistência pré-natal e qualificação profissional, em âmbito individual e coletivo.
Objective: to describe the perceptions of resident nurses in the process of qualifying for antenatal care about gender issues in the nursing consultation. Method: qualitative study, carried out with twelve nurses in qualification, in the modality of residency, in antenatal care services, in the city of Rio de Janeiro. The semi-structured interviews took place from October to November 2016. Thematic content analysis was applied. Results: gender norms are related to traditional values ââand behaviors associated with maternity and paternity. The inequities arising from these norms are seen as the cause of violence against women and limited male involvement in pregnancy. There are restrictions from a gender perspective on services, although there are men who seek more active parenting and same-sex couples who resort to antenatal care. Conclusion: intervention proposals focusing on this perspective are necessary in antenatal care and professional qualification, individually and collectively.
Objetivo: describir las percepciones de enfermeras residentes en proceso de calificación para atención prenatal sobre temas de género en la consulta de enfermería. Método: estudio cualitativo, realizado con doce enfermeras en calificación, modalidad de residencia, en servicios de atención prenatal, en la ciudad de Rio de Janeiro. Las entrevistas semiestructuradas ocurrieron de octubre a noviembre de 2016. Se aplicó el análisis de contenido temático. Resultados: normas de género están relacionadas con valores y comportamientos tradicionales asociados a maternidad y paternidad. Las desigualdades de estas normas son la causa de la violencia contra la mujer y de la limitada participación masculina en el embarazo. Hay restricciones desde una perspectiva de género en los servicios, aunque algunos hombres busquen una paternidad más activa y parejas homoafectivas recurran a la atención prenatal. Conclusión: propuestas de intervención centradas en esta perspectiva son necesarias en la atención prenatal y calificación profesional, individual y colectiva.