Effect of American genomic ancestry on severe toxicities in children with acute lymphoblastic leukemia in the Amazon region.

BACKGROUND: Acute Lymphoblastic Leukemia (ALL) is a neoplasm of the hematopoietic system characterized by a clonal expansion of abnormal lymphocyte precursor cells. ALL is the most common form of cancer in children, but despite advances in treatment, it can still be fatal. Ethnic differences influence survival rates, and genomic ancestry plays an important role, especially in mixed-race populations such as Latin America. This study aims to analyze the influence of genomic ancestry on toxicity in children with ALL in the Amazon region. METHODS: The study included 171 patients (protocol number 119,649/2012-Ethics Committee) with ALL treated at a pediatric treatment center in Belém do Pará, in the Brazilian Amazon. The patients were submitted to the BFM protocol of induction therapy for ALL. Toxicity was assessed based on laboratory tests and adverse events, classified according to the CTC-NCI guide. Genomic ancestry was determined using autosomal informative markers. RESULTS: The majority of children (94.74%) developed some type of toxicity during treatment, 87.04% of which were severe. Infectious toxicity was the most common, present in 84.8% of cases, 77.24% of which were severe. Amerindian ancestry showed an association with the risk of severe general toxicity and severe infectious toxicity, with a contribution of 35.0% demonstrating a significant increase in risk. In addition, post-induction refractoriness and relapse were also associated with an increased risk of death. CONCLUSION: This study highlights the influence of Amerindian genomic ancestry on response to therapy and toxicity in children with ALL in the Amazon region. Understanding these associations can contribute to personalizing treatment and improving clinical outcomes.

Extensão universitária na promoção de ações educativas para o trânsito: Relato de Experiências de um projeto desenvolvido em Marabá (PA)

Este é um estudo descritivo que tem como objetivo relatar a experiência vivenciada no projeto de extensão denominado "Educa Mais Trânsito", desenvolvido por discentes e docentes da Faculdade de Saúde Coletiva, da Universidade Federal do Sul e Sudeste do Pará (Unifesspa), idealizado para realizar ações educativas em saúde, no município de Marabá (PA), frente aos muitos acidentes de trânsito na região. No Brasil, o Estado do Pará caracteriza-se como o de maior ocorrência, sendo 6.398 internações e 1.159 óbitos apenas em 2018. Em Marabá, no sudeste do estado, registrou-se 296 acidentes e 76 óbitos no mesmo período. Primeiramente, foram realizadas rodas de conversas envolvendo acadêmicos do curso de Bacharelado em Saúde Coletiva com profissionais que atuam em órgãos ligados a segurança e assistência no trânsito da região. Posteriormente, houve a realização de palestras educativas, peças teatrais (público infantil e jovens), jogos educativos em quatro escolas do município, bem como a realização do I Simpósio de Educação no Trânsito de Marabá. Durante as atividades, observou-se a importância das práticas educativas com foco na promoção da conscientização, sensibilização e mobilização não só de estudantes da região mas, também, do envolvimento deste público com órgãos governamentais no que tange a regulamentação dos eventos do trânsito do município. Neste contexto, reforça-se a importância da parceria universidade e comunidade na formação de cidadãos/ãs conhecedores dos problemas de sua localidade com a sensibilização sobre os sérios problemas de saúde pública como os acidentes de trânsito através de projetos extensionistas.

The Genomic Profile Associated with Risk of Severe Forms of COVID-19 in Amazonian Native American Populations.

Genetic factors associated with COVID-19 disease outcomes are poorly understood. This study aimed to associate genetic variants in the SLC6A20, LZTFL1, CCR9, FYCO1, CXCR6, XCR1, and ABO genes with the risk of severe forms of COVID-19 in Amazonian Native Americans, and to compare the frequencies with continental populations. The study population was composed of 64 Amerindians from the Amazon region of northern Brazil. The difference in frequencies between the populations was analyzed using Fisher's exact test, and the results were significant when p ≤ 0.05. We investigated 64 polymorphisms in 7 genes; we studied 47 genetic variants that were new or had impact predictions of high, moderate, or modifier. We identified 15 polymorphisms with moderate impact prediction in 4 genes (ABO, CXCR6, FYCO1, and SLC6A20). Among the variants analyzed, 18 showed significant differences in allele frequency in the NAM population when compared to others. We reported two new genetic variants with modifier impact in the Amazonian population that could be studied to validate the possible associations with COVID-19 outcomes. The genomic profile of Amazonian Native Americans may be associated with protection from severe forms of COVID-19. This work provides genomic data that may help forthcoming studies to improve COVID-19 outcomes.

Influence of APOE locus on poor prognosis of COVID-19.

The COVID-19 pandemic has infected over 25 million of people worldwide, 5% of whom evolved to death and, among of the active cases, more than 60 thousand are classified as critical or severe. Recent studies revealed that ApoE, a protein encoded by APOE gene, may increase the risk of severe COVID-19 cases. ApoE has been involved with prevention of tissue damage and promotion of adaptative immune response in the lungs. This study investigated frequencies distribution of alleles that alter the ApoE expression in lung tissues to trace a profile of these variants and associate them to COVID-19 clinical outcomes. Data about APOE expression levels was obtained from the Genotype-Tissue Expression Project and the allele frequencies of APOE variants was acquired from the populations included in the phase 3 release of the 1000 Genomes Project. A total of 128 variants showed a significant impact on the APOE expression in lung tissues (p < 0.0001). Linkage Disequilibrium analysis revealed that 98 variants were closely grouped into seven distinct haplotype blocks, of which six were composed of variants that significantly decrease APOE gene expression in the lungs. Most of the haplotypes with higher impact on APOE expression showed greater frequencies in Europeans and lower in Africans, which implies that European populations might be more susceptible to SARS-CoV-2 infection. The present study indicates a potential genetic contribution of APOE expression-modifying variants in modulating the prognosis of COVID-19.

Letalidade da COVID-19 entre profissionais de saúde no Pará, Brasil / Lethality of COVID-19 among healthcare professionals in Pará, Brazil / Letalidad por COVID-19 entre profesionales de salud en Pará, Brasil

Objetivo: analisar a letalidade da COVID-19 por sexo e idade entre os profissionais de saúde do Estado Pará, Brasil. Método: estudo epidemiológico e observacional, com utilização de dados secundários públicos sobre casos e óbitos acumulados por COVID-19 e dados demográficos, entre março e outubro de 2020. O número de casos e óbitos por COVID-19 ocorridos entre profissionais de saúde foram comparados em relação à idade e ao sexo pelo teste qui-quadrado, seguido por regressão logística pelo método Backward Stepwise de Wald. Resultados: entre os 15.332 casos confirmados de COVID-19, 70,3% eram do sexo feminino e 61,3% com idade entre 30 a 49 anos (39,2±11,6 anos). Registraram-se 97 óbitos, com uma taxa de letalidade de 0,6%. A probabilidade de óbito foi 52,8 vezes (20,7-134,5) e 4,0 vezes (2,5-6,2) maior entre jovens e homens quando comparados às demais notificações. Conclusão: a taxa de letalidade entre os profissionais de saúde é alta, especialmente entre homens jovens. Este é um alerta sobre os impactos da doença entre os trabalhadores da saúde e suscita ao poder público, especificamente ao setor saúde melhores condições de trabalho e políticas de saúde do trabalhador.(AU)

Objective: to analyze the lethality of COVID-19 by sex and age among health professionals in the state of Pará, Brazil. Method: epidemiological and observational study, using public secondary data on cases and deaths accumulated by COVID-19 and demographic data, between March and October 2020. The number of cases and deaths by COVID-19 that occurred among health professionals were compared in relation to age and sex using the chi-square test, followed by logistic regression using Wald's Backward Stepwise method. Results: among the 15,332 confirmed cases of COVID-19, 70.3% were female and 61.3% aged between 30 and 49 years (39.2 ± 11.6 years). 97 deaths were recorded, with a fatality rate of 0.6%. The probability of death was 52.8 times (20.7-134.5) and 4.0 times (2.5-6.2) higher among young men and men when compared to other reports. Conclusion: the lethality rate among health professionals is high, especially among young men. This is an alert about the impacts of the disease among health workers and raises the public authorities, specifically the health sector, better working conditions and worker health policies.(AU)

Objetivo: analizar la letalidad de COVID-19 por sexo y edad en profesionales de la salud en el estado de Pará, Brasil. Método: estudio epidemiológico y observacional, utilizando datos secundarios públicos sobre casos y defunciones acumulados por COVID-19 y datos demográficos, entre marzo y octubre de 2020. Se comparó el número de casos y defunciones por COVID-19 ocurridos entre profesionales de la salud en relación con edad y sexo usando la prueba de chi-cuadrado, seguida de regresión logística usando el método de Wald Backward Stepwise. Resultados: entre los 15.332 casos confirmados de COVID-19, el 70,3% eran mujeres y el 61,3% tenían entre 30 y 49 años (39,2 ± 11,6 años). Se registraron 97 muertes, con una tasa de letalidad del 0,6%. La probabilidad de muerte fue 52,8 veces (20,7-134,5) y 4,0 veces (2,5-6,2) más grande entre hombres y jóvenes en comparación con otros informes. Conclusión: la tasa de letalidad entre los profesionales de la salud es alta, especialmente entre los hombres jóvenes. Se trata de una alerta sobre los impactos de la enfermedad entre los trabajadores de la salud y plantea a las autoridades públicas, específicamente al sector salud, mejores condiciones laborales y políticas de salud laboral.(AU)

Characterization of pharmacogenetic markers related to Acute Lymphoblastic Leukemia toxicity in Amazonian native Americans population.

Acute Lymphoblastic Leukemia (ALL) is the most common cancer in children. Differences are found among ethnic groups in the results of the treatment of pediatric ALL. In general, children with a high level of native American ancestry tend to respond less positively to ALL treatments, which may be related to specific genomic variants found in native American groups. Despite the evidence, few data are available on the distribution of the pharmacogenomic variants relevant to the treatment of ALL in traditional Amerindian populations, such the those of the Amazon region. Given this, the present study investigated 27 molecular markers related to the treatment of ALL in Amerindians from Brazilian Amazonia and compared the frequencies with those recorded previously on five continents, that are available in the 1,000 Genomes database. The variation in the genotype frequencies among populations was evaluated using Fisher's exact test. The False Discovery Rate method was used to correct the results of the multiple analyses. Significant differences were found in the frequencies of the majority of markers between the Amerindian populations and those of other regions around the world. These findings highlight the unique genetic profile of the indigenous population of Brazilian Amazonia, which may reflect a distinct therapeutic profile for the treatment of ALL in these populations.

Association of genes ARID5B, CEBPE and folate pathway with acute lymphoblastic leukemia in a population from the Brazilian Amazon region.

Acute Lymphoblastic Leukemia (ALL) is the most common childhood neoplasia. Studies have shown that susceptibility to ALL may be modulated by genetic variables. Our study investigated 21 genetic variants in the susceptibility of the population of the Brazilian Amazon region to B-cell ALL. The variants of the genes GGH, CEBPE, ARID5B, MTHFR and MTHFD1 were related to a protective effect against the development of ALL, whereas the variant of the gene ATIC was associated with a risk effect. The results suggest that genetic variants analyzed modulate of the risk of developing ALL in the studied population.

Pharmacogenomics and variations in the risk of toxicity during the consolidation/maintenance phases of the treatment of pediatric B-cell leukemia patients from an admixed population in the Brazilian Amazon.

The treatment of Acute Lymphoblastic Leukemia (ALL) in children has a high clinical success rate, although toxicological complications are frequent, and often result in the interruption of the treatment. Various studies have shown that toxicities resulting from the treatment are influenced by pharmacogenetic variants. Most of this research has focused on relatively homogeneous populations, and the influence of these variants in highly admixed populations, such as that of Brazil, is still poorly understood. The present study investigated the association between pharmacogenetic variants and severe toxicities in pediatric B-cell ALL patients from an admixed population of the Brazilian Amazon. The rs2306283 (of SLCO1B1) mutant allele increased the risk of neurotoxicity threefold, and the homozygous mutant rs9895420 (of ABCC3) genotype was associated with a fivefold increase in protection against severe gastrointestinal toxicity. This indicates that the rs2306283 and rs9895420 polymorphisms may be relevant to the prediction of severe toxicity in pediatric ALL patients.

Correction to: Effect of genetic ancestry to the risk of susceptibility to gastric cancer in a mixed population of the Brazilian Amazon.

Following publication of the original article [1], the authors requested a correction to the name of one of the co-authors. The correct name Marianne Rodrigues Fernandes, not Marianne Fernandes Rodrigues.

Effect of genetic ancestry to the risk of susceptibility to gastric cancer in a mixed population of the Brazilian Amazon.

BACKGROUND: Global literature describes differences in the incidence of gastric cancer among populations. For instance, Europeans have lower incidence rates of gastric cancer in relation to Latin and Asian populations, particularly Korean and Japanese populations. However, only a few studies have been able to verify the occurrence of gastric cancer in admixed populations with high interethnic degree mix, such as the Brazilian Amazon region. RESULTS: We observed an increase in European ancestry in the control group compared to the case group (47% vs. 41%). Using increments of 10%, compared to categorical distribution of European ancestry in the sample, we found a difference in the contribution between cases and controls (p = 0.03). Multiple logistic regression was performed to determine the influence of European ancestry in susceptibility to gastric cancer in the sample. According to the adopted model, for each 10% increase in European ancestry, there is a 20% decrease chance of developing gastric cancer (P = 0.0121; OR = 0.81; 95% CI 0.54-0.83). CONCLUSION: Overall, the results suggest that a greater contribution of European ancestry can be a protective factor for the development of gastric cancer in the studied Amazon population. It can help to establish protocols able to predict susceptibility to gastric cancer in admixed populations.