Perfil epidemiológico e genético de indivíduos encaminhados para análise de mutações nos genes BRCA1 e BRCA2 em uma clínica de genética na cidade de Curitiba/PR
Tipo
TCC
Data de publicação
2024-06-13
Periódico
Citações (Scopus)
Autores
Machado, Gabriel Dziurkovski
Bretzke, Gabriela Cristina
Bretzke, Gabriela Cristina
Orientador
Wormsbecker, Lya Regina Mikami
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Título de Volume
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Introdução: O Câncer de Mama e Ovário Hereditário (HBOC) é uma síndrome neoplásica hereditária autossômica dominante que aumenta a probabilidade de carcinogênese em mama, ovário, próstata e pâncreas. BRCA1 e BRCA2 são os principais genes supressores tumorais relacionados a essa síndrome. Além disso, atualmente vários outros genes têm sido associados à carcinogênese de forma que os painéis genéticos multigênicos podem trazer melhor compreensão do papel patológico das variantes genéticas e seu impacto na proteína. Desta forma, esses exames fornecem informações valiosas sobre o risco de desenvolvimento neoplásico, guiando decisões médicas na medicina antecipatória e preventiva para aqueles que apresentem a síndrome HBOC. Objetivos: Caracterizar o perfil das pacientes que realizaram painel genético para câncer de mama/ovário em uma clínica de genética de Curitiba, a fim de se correlacionar o quadro clínico com as variantes encontradas. Metodologia: Estudo retrospectivo de análise de prontuários e resultados dos laudos dos exames genéticos para câncer hereditário de 250 indivíduos com indicação clínica pessoal ou familiar para a pesquisa de HBOC no período de janeiro de 2006 e fevereiro de 2024 atendidos em uma clínica de referência em genética em Curitiba. Resultados: Dos 250 indivíduos, 98,4% eram do sexo feminino e apenas 1,6% masculino. A idade média na época do diagnóstico oncológico foi de 43,65 anos (± 13,08). Ainda, 90,54% possuíam histórico de câncer de mama, 7,2% de ovário e 2,25% em outros órgãos. Ao todo, 38,4% dos pacientes possuíam ao menos uma variante heterozigota. Foram encontradas 101 variantes em 25 genes, sendo as mais frequentemente detectadas em BRCA1 (22,77%), BRCA2 (18,81%), ATM (7,92%) e CHEK2 (6,93%). Das pacientes com variantes genéticas detectadas no exame, 39,6% eram variantes patogênicas e 53,4% com significado incerto. As variantes patogênicas mais frequentes foram: c.5266dup e c.3331_3334del em BRCA1 e c.2808_2811del e c.8488-1G>A em BRCA2. Ao nosso conhecimento, 5 variantes detectadas nos genes ATM, BRCA1, BRIP1, CLCA2 e TP53 ainda não foram descritas na literatura científica da área associada a quadro clínico, especialmente de câncer. Discussão: O perfil dos participantes é mulheres jovens, com histórico familiar de câncer, principalmente de mama e ovário. Uma a cada três pacientes com quadro clínico sugestivo de HBOC possuíam alguma variante, sendo que metade das pacientes que possuíam variantes as apresentavam em outros genes que não fossem BRCA1 e BRCA2 – isso destaca a importância da solicitação de painéis expandidos. A presença de variantes patogênicas demonstraram associação com o desenvolvimento de tumores (p-valor < 0,001), especialmente de mama e ovário (p-valor = 0,018) e do tipo triplo-negativo (p-valor < 0,001). Conclusão: Este estudo ressalta a necessidade de ampliar o acesso à tecnologia de sequenciamento de nova geração para a população dependente do Sistema Único de Saúde e destaca a importância de futuras pesquisas epidemiológicas na região sul-brasileira, que ainda são escassas para entendimento do perfil genético da população local.
Introduction: Hereditary Breast and Ovarian Cancer (HBOC) is an autosomal dominant hereditary neoplastic syndrome that increases the likelihood of carcinogenesis in the breast, ovary, prostate and pancreas. BRCA1 and BRCA2 are the main tumor suppressor genes related to this syndrome. In addition, several other genes have currently been associated with carcinogenesis, so multigene genetic panels can provide a better understanding of the pathological role of genetic variants and their impact on the protein. In this way, these tests provide valuable information on the risk of neoplastic development, guiding medical decisions in anticipatory and preventive medicine for those with HBOC syndrome. Objectives: To characterize the profile of patients who underwent a genetic panel for breast/ovarian cancer at a genetics clinic in Curitiba, in order to correlate the clinical picture with the variants found. Methodology: A retrospective study analyzing the medical records and the results of the genetic test reports for hereditary cancer of 250 individuals with a personal or family clinical indication for HBOC research between January 2006 and February 2024 who were seen at a genetics reference clinic in Curitiba. Results: Of the 250 individuals, 98.4% were female and only 1.6% male. The average age at the time of cancer diagnosis was 43.65 years (± 13.08). In addition, 90.54% had a history of breast cancer, 7.2% of ovarian cancer and 2.25% of cancer in other organs. In all, 38.4% of the patients had at least one heterozygous variant. 101 variants were found in 25 genes, the most frequently detected being BRCA1 (22.77%), BRCA2 (18.81%), ATM (7.92%) and CHEK2 (6.93%). Of the patients with genetic variants detected in the test, 39.6% were pathogenic variants and 53.4% were of uncertain significance. The most frequent pathogenic variants were: c.5266dup and c.3331_3334del in BRCA1 and c.2808_2811del and c.8488-1G>A in BRCA2. To our knowledge, 5 variants detected in the ATM, BRCA1, BRIP1, CLCA2 and TP53 genes have not yet been described in the scientific literature associated with clinical conditions, especially cancer. Discussion: The profile of the participants was young women with a family history of cancer, mainly breast and ovarian. One in three patients with a clinical picture suggestive of HBOC had some variant, and half of the patients who had variants had them in genes other than BRCA1 and BRCA2 - this highlights the importance of requesting expanded panels. The presence of pathogenic variants was associated with the development of tumors (p-value < 0.001), especially breast and ovarian tumors (p-value = 0.018) and triple-negative tumors (p-value < 0.001). Conclusion: This study underscores the need to expand access to next-generation sequencing technology for the population dependent on the Unified Health System and highlights the importance of future epidemiological research in the southern Brazilian region, which is still scarce for understanding the genetic profile of the local population.
Introduction: Hereditary Breast and Ovarian Cancer (HBOC) is an autosomal dominant hereditary neoplastic syndrome that increases the likelihood of carcinogenesis in the breast, ovary, prostate and pancreas. BRCA1 and BRCA2 are the main tumor suppressor genes related to this syndrome. In addition, several other genes have currently been associated with carcinogenesis, so multigene genetic panels can provide a better understanding of the pathological role of genetic variants and their impact on the protein. In this way, these tests provide valuable information on the risk of neoplastic development, guiding medical decisions in anticipatory and preventive medicine for those with HBOC syndrome. Objectives: To characterize the profile of patients who underwent a genetic panel for breast/ovarian cancer at a genetics clinic in Curitiba, in order to correlate the clinical picture with the variants found. Methodology: A retrospective study analyzing the medical records and the results of the genetic test reports for hereditary cancer of 250 individuals with a personal or family clinical indication for HBOC research between January 2006 and February 2024 who were seen at a genetics reference clinic in Curitiba. Results: Of the 250 individuals, 98.4% were female and only 1.6% male. The average age at the time of cancer diagnosis was 43.65 years (± 13.08). In addition, 90.54% had a history of breast cancer, 7.2% of ovarian cancer and 2.25% of cancer in other organs. In all, 38.4% of the patients had at least one heterozygous variant. 101 variants were found in 25 genes, the most frequently detected being BRCA1 (22.77%), BRCA2 (18.81%), ATM (7.92%) and CHEK2 (6.93%). Of the patients with genetic variants detected in the test, 39.6% were pathogenic variants and 53.4% were of uncertain significance. The most frequent pathogenic variants were: c.5266dup and c.3331_3334del in BRCA1 and c.2808_2811del and c.8488-1G>A in BRCA2. To our knowledge, 5 variants detected in the ATM, BRCA1, BRIP1, CLCA2 and TP53 genes have not yet been described in the scientific literature associated with clinical conditions, especially cancer. Discussion: The profile of the participants was young women with a family history of cancer, mainly breast and ovarian. One in three patients with a clinical picture suggestive of HBOC had some variant, and half of the patients who had variants had them in genes other than BRCA1 and BRCA2 - this highlights the importance of requesting expanded panels. The presence of pathogenic variants was associated with the development of tumors (p-value < 0.001), especially breast and ovarian tumors (p-value = 0.018) and triple-negative tumors (p-value < 0.001). Conclusion: This study underscores the need to expand access to next-generation sequencing technology for the population dependent on the Unified Health System and highlights the importance of future epidemiological research in the southern Brazilian region, which is still scarce for understanding the genetic profile of the local population.
Descrição
Palavras-chave
variação genética , síndrome hereditária de câncer de mama e ovário , genes supressores de umor , genetic variation , hereditary breast and ovarian cancer syndrome , tumor suppressor genes