GENETIC AND DEMOGRAPHIC FACTORS OF A BRAZILIAN POPULATION SAMPLE AT-RISK OF HEREDITARY BREAST AND OVARIAN CANCER / Fatores genéticos e demográficos de uma amostra da população brasileira sob risco de síndrome de câncer de mama e ovário hereditários

Objective: Genetic-related breast cancer has a tendency to manifest earlier and to be more aggressive than sporadic cancer. There are few studies evaluating the prevalence and incidence of hereditary breast and ovarian cancer (HBOC) among Brazilians. In order to improve assistance, efforts to characterize the population at risk of HBOC could help to formulate locally designed guidelines. Methodology: Descriptive retrospective study in Hospital Erasto Gaertner's service of Oncogenetics, in Curitiba, state of Paraná, Brazil. We included individuals at-risk for HBOC, according to the National Comprehensive Cancer Network (NCCN) criteria, who had performed genetic tests for HBOC. We collected complete family history, presented as heredograms. We excluded families with inappropriate family history. Results: Of the 27 patients analyzed (total of 25 families), 7% were asymptomatic, 8% had ovarian cancer and 85% had breast cancer. Mutations were found in 29.6%, 6 cases of BRCA1, 1 of BRCA2 and 1 of TP53. Triple negative was the most common reported subtype, representing 60% of breast cancers; among patients with identified pathogenic variants, 2 were BRCA2 mutated and 1 TP53 mutated. The mean age of diagnosis was 40 years for those identified as probands on heredograms; in the generation above, it was 52,5, and in the below, 33, suggesting the antecipation phenomena Two new mutations were identified in Brazilian population, both in BRCA1: c.4258 G>A and c.5345 G>A. The most frequent NCCN criteria were number 2, 9, 8 and 4. Estimated penetrance was 22%. Conclusion: This is the first descriptive study in the population at-risk for HBOC in the state of Paraná. We could identify two new pathogenic variants of BRCA1 in Brazilian population. A comprehensive family history was included in the study, depicted as heredograms of each family. Despite the low number of patients, the main results are in agreement with previous studies

Objetivo: Os carcinomas de mama hereditários têm a tendência de se manifestar precocemente e serem mais agressivos do que os esporádicos. São poucos os estudos que avaliam a prevalência e a incidência da síndrome de câncer de mama e ovário hereditário (SCMOH) na população brasileira. No intuito de melhorar a assistência prestada, a análise das características encontradas na população em risco para SCMOH ajudaria a formulação de protocolos regionais para a abordagem desses pacientes. Metodologia: Estudo descritivo retrospectivo realizado no serviço de Oncogenética do Hospital Erasto Gaertner em Curitiba, Paraná. Incluímos indivíduos em risco para SCMOH pelos critérios estabelecidos pela National Comprehensive Cancer Network (NCCN) e que realizaram testes genéticos para SCMOH. Coletamos o histórico familiar completo, apresentado na forma de heredograma. Foram excluídas famílias com histórico familiar inapropriado. Resultados: Das 27 pacientes analisadas (total de 25 famílias), 7% eram assintomáticas, 8% tiveram câncer de ovário e 85%, câncer de mama. Mutações foram encontradas em 29,6%, sendo 6 casos de BRCA1, 1 de BRCA2 e 1 de TP53. Tumores triplo negativos foram os mais encontrados entre os subtipos, representando 60% dos carcinomas de mama; dentre os pacientes com variantes patogênicas, 2 eram de mutações em BRCA2 e 1 em TP53. A média de idade entre as pacientes foi de 40 anos entre probandas dos heredogramas; na geração superior, foi de 52,5 anos e na inferior, de 33, sugerindo o fenômeno de antecipação. Duas novas mutações foram descritas na população brasileira, as duas sendo em BRCA1: c.4258 G>A e c.5345 G>A. Os critérios NCCN mais encontrados foram os de número 2, 9, 8 e 4. A penetrância estimada foi de 22%. Conclusão: Este foi o primeiro estudo descritivo de uma população em risco para SCMOH no estado do Paraná. Encontramos duas novas mutações que não haviam sido descritas na população brasileira até então. Foi realizada a análise detalhada do histórico familiar das pacientes, sendo descrita e detalhada em heredogramas para cada família. Apesar do baixo número de indivíduos analisados, os resultados principais foram de acordo com o encontrado em estudos prévios

Factores genéticos en la carcinogénesis mamaria

El cáncer mamario es una enfermedad genética multifactorial donde intervienen los oncogenes derivados de genes celulares normales, que constituyen señales positivas de la proliferación celular y los genes supresores tumorales, que representan señales negativas de la multiplicación y diferenciación celulares. Aunque estas alteraciones que afectan células germinales originan cánceres hereditarios, en la mayoría de los casos se afectan genes en las células somáticas. A la susceptibilidad al cáncer dada por genes como BRCA1 y BCRA2, se adiciona el efecto de factores asociados al ambiente, estilos de vida y hábitos tóxicos, que determinan una compleja interrelación genes-medio que implica una activación de oncogenes y una inactivación de supresores tumorales. El objetivo de esta revisión es ofrecer una visión actualizada sobre los principales genes implicados en la carcinogénesis de mama. El tema es polémico, controversial y se investiga mucho en la actualidad.

Breast cancer is a multifactorial genenetic disease in which oncogenes derived from normal cellular genes intervene, which constitute positive signals of cellular proliferation and tumour suppressor genes and represent negative signals of cells multiplication and differentiation. Although these alterations which affect germinal cells produce inherited cancers, in most of the cases somatic cell genes are affected. To the susceptibility of cancer due to genes as BRCA1 and BCRA2, the effect of factors associated to environment, life style and toxic habits are added, these determine a complex interrelation genes-environment which imply an activation of oncogenes and inactivation of tumour suppressors. The objective of this review in to offer an updated view about the main genes implied in breast carcinogenesis. The topic is controversial y currently deeply investigated.

Pesquisa e propriedade intelectual envolvendo material humano: afinal,de quem são nossos genes? / /Research and intellectual property involving human material: after all,from whom are our genes? / /La investigación y la propiedad intelectual implicando material humano:¿al final, a quien pertenecen nuestros genes?

O presente artigo discute aspectos éticos, científicos e jurídicos sobre o patenteamento de genes humanos,partindo de um contexto histórico sobre propriedade intelectual de seres vivos e passando pela decisão da Suprema Corte dos EUA relativa ao caso Myriad Genetics, conflito em torno da patente dos genes BRCA1e BRCA2, relacionados ao câncer de mama e de ovário. Além disso, o artigo aborda diplomas normativos sobre o assunto, considerando tanto a legislação brasileira quanto a internacional. Por fim, contrapõe posições distintas sobre patente de genes humanos, adotando posicionamento crítico que o assunto merece...

This article discusses ethical, scientific and legal aspects of the patenting of human genes, startingfrom a historical context of intellectual property of living beings and passing through the decision ofthe US Supreme Court in Myriad Genetics case, conflict over patent of the genes BRCA1 and BRCA2,related to breast cancer and ovarian cancer. Moreover, the article discusses regulatory instrumentson the subject, considering both the Brazilian and international legislation. Finally, it contrastsdifferent positions on patent of human genes, adopting critical position that this matter deserves...

Este artículo aborda los aspectos éticos, científicos y legales de las patentes de genes humanos, a partir de uncontexto histórico de la propiedad intelectual de los seres vivos y pasando por la decisión de la Corte Suprema deEstados Unidos en el caso Myriad Genetics, el conflicto sobre patentes de los genes BRCA1 y BRCA2 relacionadoscon el cáncer de mama y cáncer de ovario. Además, el artículo analiza los instrumentos normativos sobre eltema, teniendo en cuenta tanto la legislación brasileña como internacional. Por último, contrasta diferentesposiciones sobre las patentes de los genes humanos, y adopta una posición crítica que este asunto merece...

Application of gene sequencing in detection of BRCA1/2 gene mutations in breast cancer patients and risk assessment / 中华检验医学杂志

Objective To explore the mutation spectrum of breast and ovarian cancer susceptibility gene 1/2 (BRCA1/2) which was related to breast cancer in female residents of Wuhan,and assess the relation of gene mutation and risk of suffering breast cancer.Methods 128 cases of female individuals,including 58 cases of breast cancer after surgery,70 cases of benign breast disease,and 50 femal hcalthy volunteers were selected by simple randon sampling from Department of Breast Surgery of Renmin Hospital of Wuhan University.BRCA1/2 gene was sequenced and compared with the standard template sequence to explore the possible mutations.Results In the breast cancer group,mutation emerged in 11 cases and the mutation rate was 19.0％ (11/58),including 8 cases of the BRCA1 gene mutations (3 cases of 185 del AG,5 case of 5382 ins C) and 3 cases of the BRCA2 gene mutations (2 cases of 6174 del T,1 case of C5773T) ; in the benign breast disease group,mutation emerged in 5 cases,the mutation rate was 7.1％(5/70),including 4 cases of the BRCA1 gene mutations (1 case of 185 del AG,3 cases of 5382 ins C),and 1 case of the BRCA2 gene mutation (6174 del T).There was no mutation detected in healthy control group.The mutation rate of the breast cancer group was significantly higher than that of benign breast disease group and healthy control group (x2 =4.05,10.56,P ＜ 0.05); However,there was no significant difference between benign breast disease group and healthy control group (x2 =3.73,P ＞0.05).Conclusions The mutation of BRCA1 gene (185 del AG,5382 ins C) and BRCA2 gene (6174 del T,C5773T) is in the presence of female residents in Wuhan.Furthermore,the mutation in BRCA1/2 gene increases the risk of breast cancer.