Cognitive abilities tend to decline with aging, with variation between individuals, and many studies seek to identify genetic biomarkers that more accurately anticipate risks related to pathological aging. We investigated the influence of BDNF, NTRK2, and FNDC5 single nucleotide polymorphisms (SNPs) on the cognitive performance of young and older adults with contrasting educational backgrounds. We addressed three questions: (1) Is education associated with reduced age-related cognitive decline? (2) Does the presence of SNPs explain the variation in cognitive performance observed late in life? (3) Is education differentially associated with cognition based on the presence of BDNF, NTRK2, or FNDC5 polymorphisms? We measured the cognitive functions of young and older participants, with lower and higher education, using specific and sensitive tests of the Cambridge Automated Neuropsychological Test Assessment Battery. A three-way ANOVA revealed that SNPs were associated with differential performances in executive functions, episodic memory, sustained attention, mental and motor response speed, and visual recognition memory and that higher educational levels improved the affected cognitive functions. The results revealed that distinct SNPs affect cognition late in life differentially, suggesting their utility as potential biomarkers and emphasizing the importance of cognitive stimulation that advanced education early in life provides.

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer in the world. Single nucleotide variants (SNVs) in miRNA and genes encoding proteins of the miRNA synthesis complex (SC) may affect the processing of drugs used in the treatment of ALL, resulting in treatment-related toxicities (TRTs). We investigated the role of 25 SNVs in microRNA genes and genes encoding proteins of the miRNA SC, in 77 patients treated for ALL-B from the Brazilian Amazon. The 25 SNVs were investigated using the TaqMan® OpenArray™ Genotyping System. SNVs rs2292832 (MIR149), rs2043556 (MIR605), and rs10505168 (MIR2053) were associated with an increased risk of developing Neurological Toxicity, while rs2505901 (MIR938) was associated with protection from this toxicity. MIR2053 (rs10505168) and MIR323B (rs56103835) were associated with protection from gastrointestinal toxicity, while DROSHA (rs639174) increased the risk of development. The rs2043556 (MIR605) variant was related to protection from infectious toxicity. SNVs rs12904 (MIR200C), rs3746444 (MIR499A), and rs10739971 (MIRLET7A1) were associated with a lower risk for severe hematologic toxicity during ALL treatment. These findings reveal the potential for the use of these genetic variants to understand the development of toxicities related to the treatment of ALL in patients from the Brazilian Amazon region.

Breast cancer is the most common malignant disease and the leading cause of mortality among women worldwide. Antineoplastic chemotherapy is one of its primary treatments, typically based on the class of drugs known as taxanes. Despite their proven therapeutic efficacy, these drugs can induce severe toxicities, leading to dose limitations or even treatment discontinuation. The objective of this study was to describe the clinical-epidemiological profile, risk factors, and toxicities of taxane-based chemotherapy treatment in women with breast cancer in the Amazon region. This is a cross-sectional, quantitative, and descriptive study conducted with 300 women diagnosed with breast cancer undergoing taxane treatment. Most patients were in the 40-49 age range, of brown ethnicity, and had completed elementary school. The majority of patients had risk factors such as alcoholism and a sedentary lifestyles. Most women had their first pregnancy between the ages of 18 and 21, breastfed their children, had menarche between the ages of 12 and 13, and were pre-menopausal and with a family history of cancer. The most frequent histological type was non-special invasive carcinoma and the Luminal B subtype. Most participants in this study showed taxane toxicity, with neurotoxicity being the most frequent. These findings reveal the importance of early detection, comprehensive risk factors, and effective management of treatment toxicities to improve patient outcomes in breast cancer care in the Amazon region.

O câncer gástrico é um importante problema de saúde pública, considerado o quinto câncer mais diagnosticado no mundo. A metástase peritoneal é uma das principais causas de mortalidade relacionadas ao câncer gástrico. A hipermetilação de genes supressores de tumor é um fator promissor para o desenvolvimento de biomarcadores preditivos. Em tumores gástricos, a expressão reduzida do gene supressor CDH1 contribui para a invasão tumoral e desencadeamento de metástases. Nosso objetivo foi avaliar o perfil de metilação da região promotora do gene CDH1 como indicador de metástase peritoneal em pacientes com câncer gástrico. O perfil de metilação de CDH1 foi avaliado em 47 amostras de lavados peritoneais de pacientes com câncer gástrico por PCR de sequenciamento de bissulfito (BSP). Trinta e três sítios CpGs na região do promotor CDH1 foram avaliados individualmente. Amostras com ≥ 10% de sítios CpGs metilados foram consideradas hipermetiladas. A análise estatística foi realizada pelo teste Exato de Fisher, utilizando o programa R-Studio (p≤0,05). Vinte e nove (62%) amostras apresentaram hipermetilação na região promotora de CDH1, com metilação preferencial nos sítios CpGs localizados na região 5' a montante do gene. A análise estatística mostrou que a hipermetilação de CDH1 foi significativamente diferente em pacientes com estágios avançados de profundidade de invasão do tumor (p=0,03). Nossos resultados sugerem que a análise de metilação do gene CDH1 é uma ferramenta útil na predição de progressão e invasividade tumoral em pacientes com câncer gástrico e pode ter um grande impacto para o campo da medicina de precisão do câncer.

Gastric cancer is a major public health problem, considered the fifth most frequently diagnosed cancer worldwide. Peritoneal metastasis is the main causes of mortality related to gastric cancer. The hypermethylation of tumor suppressors genes is a promising factor for the development of predictive biomarkers. In gastric tumors, reduced expression of CDH1 suppressor gene contributes to tumor invasion and triggering metastasis. We aim to evaluate the promoter region methylation profile of the CDH1 gene as a peritoneal metastasis indicator in patients with gastric cancer. CDH1 methylation profile were evaluate in 47 samples of peritoneal washes from patients with gastric cancer by bisulfite sequencing PCR (BSP). Thirty-three CpGs sites in the CDH1 promoter region were individually evaluated. Samples with ≥ 10% of methylated CpGs sites were considered hypermethylated. Statistical analysis was performed by Fisher's Exact test using R-Studio program (p≤0.05). Twenty-nine (62%) samples showed hypermethylation in the promoter region of CDH1, with preferential methylation at the CpGs sites located in the region 5' upstream from gene. Statistical analysis showed that CDH1 hypermethylation was significantly different in patients with advanced stages of tumor depth of invasion (p=0.03). Our results suggest that CDH1 gene methylation analysis is a useful tool in predicting tumor progression and invasiveness in gastric cancer patients and could have a major impact for the field of precision cancer medicine.

e20538 Background: Lung cancer is one of the most frequent neoplasms in the world, representing 11.4% of all registered cancers, and is responsible for 18% of cancer deaths. It is divided into two categories, small cell lung cancer, responsible for 15% of cases; and non-small cell lung cancer (NSCLC), which represents 85% of cases. The most well-known risk factor for the development of lung cancer is smoking, due to substances contained in tobacco associated with inflammation and carcinogenesis. Pulmonary carcinogenesis is a complex and gradual process, with synergistic and complex interactions between environmental risk factors and individual genetic susceptibility. The aim of this study was to investigate possible associations between TP53, PAR1, and CCR5 gene polymorphism for susceptibility to NSCLC in the Amazon. Methods: This is a pilot, case-control study, which included 263 subjects, 67 patients with NSCLC and 196 healthy subjects. The samples were analyzed for TP53 (rs17880560), PAR1 (rs11267092), and CCR5 (rs333) gene polymorphism, genotyped in PCR, followed by fragment analysis. To avoid misinterpretation due to population substructure, we applied a previously developed set of 61 informative ancestral markers that were genotyped by multiplex PCR. We used logistic regression to identify differences in genotypic frequencies between individuals with and without lung cancer. Results: We observed that some genotypes were associated with protection for NSCLC: TP53 gene LED/DEL genotype (p = 0.041, OR: 0.510, 95%CI: 0.267-0.974); DEL/DEL genotype of the PAR1 gene (p = 0.023, OR: 0.471, 95%CI: 0.247-0.971); and also the INS/INS genotype of the CCR5 gene (p = 0.033, OR: 0.331, 95%CI: 0.120-0.917). Conclusions: TP53 (rs17880560), PAR1 (rs11267092) and CCR5 (rs333) gene variants were significantly associated with NSCLC in patients from the Amazon. The validation of these findings may favor, in the future, the screening of individuals, facilitating the institution of preventive measures personalized, early diagnosis, consequently reducing the cost for health services and mortality from this malignant neoplasm. Keywords: Genetic Polymorphism; TP53; PAR1; CCR5; Biomarker; Non-Small Cell Lung Cancer.

Tuberculosis (TB) is a chronic infection caused by Mycobacterium tuberculosis (Mtb) with high incidence and mortality. Studies reported that host genetic variants might be associated with the risk of tuberculosis. The aim of this study was to perform an association study between 26 single nucleotide polymorphisms (SNPs) and tuberculosis and evaluate whether these SNPs may confer risk factors to tuberculosis in the Amazon population. There were 52 males and 126 females, with total of 178 healthy controls. Genotyping was performed using TaqMan Open Array Genotyping. Ancestry-informative markers were used to estimate the ancestral proportions of the individuals in the case and control groups. The results indicated that the SNPs rs10035440 (DROSHA), rs7372209 (miR26-a1), rs1834306 (miR100), rs4919510 (miR608), and rs10739971 (pri-let-7a-1) were significantly associated with high risk and rs3746444 (miR499) and rs6505162 (miR423), with low risk of developing tuberculosis in the Amazon population. Our study concluded that seven miRNA polymorphisms were associated with tuberculosis. Our study contributes to a better understanding of TB pathogenesis and may promote the development of new diagnostic tools against M. tuberculosis infection.

Os casos de câncer aumentaram mundialmente. Estimam-se, para o Brasil, 14.700 novos casos de carcinoma de células escamosas oral (CCEO) para o biênio 2018-2019. O câncer pode ser prevenido com estilo de vida saudável e com análises de microRNAs, biomarcadores envolvidos na oncogênese. O objetivo deste estudo foi avaliar a associação do nível de expressão do microRNAs da família Let-7 (miR-let-7c) relacionando-o a fatores epigenéticos e socioeconômicos de indivíduos residentes no município de Belém (Pará). A amostra, apesar da heterogeneidade, não apresentou diferenças estatísticas na expressão do microRNA let-7c mostrando que, no processo da formação da população de Belém, este biomarcador não sofre influência da ancestralidade genômica, fazendo dele, um bom marcador de risco, podendo, ser utilizado como ferramenta em estudos comparativos relacionados ao câncer ou doenças infectocontagiosas. Um vasto campo e uma infinidade de biomarcadores podem ainda ser identificados e analisados, resultando em tratamentos menos invasivos, com melhores prognósticos.

Fluoropyrimidines are one of the most used drug class to treat cancer patients, although they show high levels of associated toxicity. This study analyzed 33 polymorphisms in 17 pharmacogenes involved with the pharmacogenomics of fluoropyrimidines, in gastrointestinal cancer patients undergoing fluoropyrimidine-based treatment in the Brazilian Amazon. The study population was composed of 216 patients, 92 of whom have an anatomopathological diagnosis of gastric cancer and 124 of colorectal cancer. The single nucleotide polymorphisms (SNP) were genotyped by allelic discrimination using the TaqMan OpenArray Genotyping technology, with a panel of 32 customized assays, run in a QuantStudio ™ 12K Flex Real-Time PCR System (Applied Biosystems, Life Technologies, Carlsbad USA). Ancestry analysis was performed using 61 autosomal ancestry informative markers (AIMs). The study population show mean values of 48.1% European, 31.1% Amerindian, and 20.8% African ancestries. A significant risk association for general and severe toxicity was found in the rs4451422 of FPGS (p = 0.001; OR 3.40; CI 95% 1.65–7.00 and p = 0.006; OR 4.63; CI 95% 1.56–13.72, respectively) and the rs9524885 of ABCC4 (p = 0.023; OR 2.74; CI 95% 1.14–6.65 and p = 0.024; OR 5.36; IC 95% 1.24–23.11, respectively) genes. The rs760370 in the SLC29A1 gene (p = 0.009; OR 6.71; CI 95% 1.16–8.21) and the rs1801133 in the MTHFR toxicity (p = 0.023; OR 3.09; CI 95% 1.16–8.21) gene also demonstrated to be significant, although only for severe toxicity. The results found in this study did not have statistics analysis correction. Four polymorphisms of the ABCC4, FPGS, SLC29A1, and MTHFR genes are likely to be potential predictive biomarkers for precision medicine in fluoropyrimidine-based treatments in the population of the Brazilian Amazon, which is constituted by a unique genetic background.

It is known that abnormal expression of miRNAs in the gastric cancer (GC) contributes to its carcinogenesis. Therefore, ingestion of commercial (usual) water on a daily basis may be a contributing factor for the occurrence of alterations in the gastric mucosal. In this study, it was evaluated the expression of the miRNAs miR-29c, miR-7, miR-155, and miR-135b in the gastric tissue of patients with gastritis before and after the consumption of alkaline water (pH range from 8.0 to 10.0), as well as the clinic pathological characteristics. Methods: 50 subjects from the Amazon region, diagnosed with gastritis that routinely used commercial (usual) water with a pH lower than 5.0, were enrolled to change the consume water to a pH of 8.5 to 10.0 for 5 months. Results: Endoscopic findings of gastritis were such different (less severe disease), P = 0.024; in 43% diagnosed with moderate gastritis upfront esophagogastroduodenoscopy (EGD) presented mild gastritis after the consumption of alkaline water, according to study methods; there were no worsening gastritis and there were a significant increase in the expression of miR-135b (P = 0.039) and miR-29c (P = 0.039). Conclusion: Modified pH range water (from 8.0 to 10.0) ingested for 5 months was able lead to a less severe gastritis according to the Sidney classification system, suggesting that this lifestyle change represented a clinical benefit in patients with gastritis on the Amazon region. In addition, higher expression of miR-135b and miR-29c was observed after the consumption of alkaline water for 5 months.

Dataset generated and analyzed by Cavalcante et al.

AbstractThe DesignOBS project was created to collect, map and interpret data about the Portuguese Design Ecosystem, providing supportive information for decision making. This study takes advantage of a participative Design perspective to define and test an observation process via a case based on Design doctorates undertaken in Portugal. It emphasises the need for additional participatory analysis and curation by experts to evaluate and develop more reliable information about the discipline. Moreover, it develops recommendations that can enhance the communicability of Design doctorates.

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.

Abstract Background Apoptosis is a type of cell death involved in different pathways inherent to the cell and the evasion from this mechanism has been related to cancer, although this process remains not very well comprehended. Gastric cancer (GC) is one of the most incident and aggressive types of cancer worldwide. In this study, we analyzed the distribution of INDEL variants in GC patients (Case) and individuals from the general population (Control) from the Amazon region, in which GC is remarkably frequent. Methods A panel of nine INDEL markers in apoptosis-related genes (BCL2 rs11269260, CASP3 rs4647655, CASP8 rs3834129 and rs59308963, CASP9 rs4645982 and rs61079693, FADD rs4197, FAS rs10562972 and TP53 rs17880560) was developed and genotyped by multiplex PCR in both groups. Results In our analyses, only marker rs4197 (FADD gene) was associated to GC development as follows: INS/DEL genotype of rs4197 increasing in about 2-fold the chances of developing this type of cancer (P = 0.046; OR = 1.940; 95%CI = 1.011–3.725). Conclusion Our results suggest that rs4197 (FADD gene) might play a role in gastric carcinogenesis in the investigated population. More studies are needed to clarify this relation. Here, we highlight the importance of investigating INDEL variants in genes involved in apoptosis.

Colorectal (CRC) and gastric (GC) cancers are associated with increased morbidity and mortality. Single nucleotide polymorphisms (SNPs) of xenobiotic metabolism and transporter genes may play a role in the individual responses to exposure to substances implicated in susceptibility to cancer. The investigation of the genetic variation related to the activation and detoxification of xenobiotics may thus help to clarify the prevalence of neoplasms. We analyzed the role of 30 SNPs in xenobiotic-metabolizing and transporter genes in susceptibility to CRC and GC. The study included individuals diagnosed with CRC (n = 121) and GC (n = 95), and 141 controls (non-cancer patients) from the population of Belém, in the Brazilian Amazon. The results indicated an association between the polymorphisms rs2231142 (P = 0.013; OR = 3.01; 95% CI = 1.26-7.13), in the ABCG2 gene, and rs1801159 (P = 0.03; OR = 2.35; 95% CI = 1.14-5.05), in DPYD gene, with the risk of developing GC. The polymorphism rs17116806 of the DPYD gene was found to be associated with a lower risk of developing gastric (P≤0.0001; OR = 0.043; 95% CI = 0.015-0.12) or colorectal (P≤0.0001; OR = 0.076; 95% CI = 0.33-0.18) cancers, indicating that the same variant may play a similar role in different types of cancer tissue. Additionally, the carriers of the TT genotype of the polymorphism in the ABCB1 gene (rs1128503) presented a reduced probability of developing CRC (P = 0.0001; OR = 0.16; 95% CI = 0.06-0.41) as well as GC (P = 0.007; OR = 0.27; 95% CI = 0.1-0.7). Our findings indicate that polymorphisms in xenobiotic-metabolizing and transporter genes may modulate susceptibility to colorectal and gastric cancers.

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.