Role of miRNAs in Sigmoid Colon Cancer: A Search for Potential Biomarkers.

The aberrant expression of microRNAs in known to play a crucial role in carcinogenesis. Here, we evaluated the miRNA expression profile of sigmoid colon cancer (SCC) compared to adjacent-to-tumor (ADJ) and sigmoid colon healthy (SCH) tissues obtained from colon biopsy extracted from Brazilian patients. Comparisons were performed between each group separately, considering as significant p-values < 0.05 and |Log2(Fold-Change)| > 2. We found 20 differentially expressed miRNAs (DEmiRNAs) in all comparisons, two of which were shared between SCC vs. ADJ and SCC vs. SCH. We used miRTarBase, and miRTargetLink to identify target-genes of the differentially expressed miRNAs, and DAVID and REACTOME databases for gene enrichment analysis. We also used TCGA and GTEx databases to build miRNA-gene regulatory networks and check for the reproducibility in our results. As findings, in addition to previously known miRNAs associated with colorectal cancer, we identified three potential novel biomarkers. We showed that the three types of colon tissue could be clearly distinguished using a panel composed by the 20 DEmiRNAs. Additionally, we found enriched pathways related to the carcinogenic process in which miRNA could be involved, indicating that adjacent-to-tumor tissues may be already altered and cannot be considered as healthy tissues. Overall, we expect that these findings may help in the search for biomarkers to prevent cancer progression or, at least, allow its early detection, however, more studies are needed to confirm our results.

New insights on intercontinental origins of paternal lineages in Northeast Brazil.

BACKGROUND: The current Brazilian population is the product of centuries of admixture between intercontinental founding groups. Although previous results have revealed a heterogeneous distribution of mitochondrial lineages in the Northeast region, the most targeted by foreign settlers during the sixteenth century, little is known about the paternal ancestry of this particular population. Considering historical records have documented a series of territorial invasions in the Northeast by various European populations, we aimed to characterize the male lineages found in Brazilian individuals in order to discover to what extent these migrations have influenced the present-day gene pool. Our approach consisted of employing four hierarchical multiplex assays for the investigation of 45 unique event polymorphisms in the non-recombining portion of the Y-chromosome of 280 unrelated men from several Northeast Brazilian states. RESULTS: Primary multiplex results allowed the identification of six major haplogroups, four of which were screened for downstream SNPs and enabled the observation of 19 additional lineages. Results reveal a majority of Western European haplogroups, among which R1b-S116* was the most common (63.9%), corroborating historical records of colonizations by Iberian populations. Nonetheless, FST genetic distances show similarities between Northeast Brazil and several other European populations, indicating multiple origins of settlers. Regarding Native American ancestry, our findings confirm a strong sexual bias against such haplogroups, which represented only 2.5% of individuals, highly contrasting previous results for maternal lineages. Furthermore, we document the presence of several Middle Eastern and African haplogroups, supporting a complex historical formation of this population and highlighting its uniqueness among other Brazilian regions. CONCLUSIONS: We performed a comprehensive analysis of the major Y-chromosome lineages that form the most dynamic migratory region from the Brazilian colonial period. This evidence suggests that the ongoing entry of European, Middle Eastern, and African males in the Brazilian Northeast, since at least 500 years, was significantly responsible for the present-day genetic architecture of this population.

Association of insertion-deletions polymorphisms with colorectal cancer risk and clinical features.

AIM: To investigate the association between 16 insertion-deletions (INDEL) polymorphisms, colorectal cancer (CRC) risk and clinical features in an admixed population. METHODS: One hundred and forty patients with CRC and 140 cancer-free subjects were examined. Genomic DNA was extracted from peripheral blood samples. Polymorphisms and genomic ancestry distribution were assayed by Multiplex-PCR reaction, separated by capillary electrophoresis on the ABI 3130 Genetic Analyzer instrument and analyzed on GeneMapper ID v3.2. Clinicopathological data were obtained by consulting the patients' clinical charts, intra-operative documentation, and pathology scoring. RESULTS: Logistic regression analysis showed that polymorphism variations in IL4 gene was associated with increased CRC risk, while TYMS and UCP2 genes were associated with decreased risk. Reference to anatomical localization of tumor Del allele of NFKB1 and CASP8 were associated with more colon related incidents than rectosigmoid. In relation to the INDEL association with tumor node metastasis (TNM) stage risk, the Ins alleles of ACE, HLAG and TP53 (6 bp INDEL) were associated with higher TNM stage. Furthermore, regarding INDEL association with relapse risk, the Ins alleles of ACE, HLAG, and UGT1A1 were associated with early relapse risk, as well as the Del allele of TYMS. Regarding INDEL association with death risk before 10 years, the Ins allele of SGSM3 and UGT1A1 were associated with death risk. CONCLUSION: The INDEL variations in ACE, UCP2, TYMS, IL4, NFKB1, CASP8, TP53, HLAG, UGT1A1, and SGSM3 were associated with CRC risk and clinical features in an admixed population. These data suggest that this cancer panel might be useful as a complementary tool for better clinical management, and more studies need to be conducted to confirm these findings.

mtDNA structure: the women who formed the Brazilian Northeast.

BACKGROUND: The distribution of mitochondrial DNA (mtDNA) lineages in Brazil is heterogeneous due to different regional colonization dynamics. Northeastern Brazil, although being an important region in terms of human imigration and ethnic admixture, has little information regarding its population mtDNA composition. Here, we determine which mitochondrial lineages contributed to the formation of the Northeastern Brazilian population. Our sample consisted of 767 individuals distributed as follows i) 550 individuals from eight Northeastern states (Piauí, Ceará, Rio Grande do Norte, Paraíba, Pernambuco, Alagoas, Sergipe, and Bahia) which were sequenced for mtDNA hypervariable segments I, II, and III; ii) 217 individuals from Alagoas and Pernambuco (previously published data). Data analysis was performed through sequence alignment and Haplogrep 2.0 haplogroup assignment tools. Furthermore, maternal ancestry distribution was contextualized and, when possible, related to historical events to better understand the biological interactions and population dynamics that occurred in this region since the beginning of colonization. RESULTS: Unexpectedly, Amerindian mitochondrial ancestry was the highest in the Northeastern region overall, followed by African, European and non-Amerindian Asian, unlike previous results for this region. Alagoas and Pernambuco states, however, showed a larger African mtDNA frequency. The Northeastern region showed an intraregional heterogeneous distribution regarding ancestral groups, in which states/mesoregions located to the north had a prevalent Amerindian ancestral frequency and those to the south had predominance of African ancestry. Moreover, results showed great diversity of European haplogroups and the presence of non-Amerindian Asian haplogroups. CONCLUSIONS: Our findings are in disagreement with previous investigations that suggest African mitochondrial ancestry is the most prevalent in the Brazilian Northeast. The predominance of Amerindian lineages exemplifies the importance of indigenous women in the formation of the population, despite intense African slave entry and conflicts with European settlers. The variable distribution of ancestral groups observed in the Northeast is in accordance with historical records showing the similarities with colonization dynamics occurred in the Amazon region and the Brazilian Southeast. Moreover, the variety of European haplogroups suggests multiple origins of founding groups, specially those found in Western European populations.

Relação entre o consumo de gordura saturada e os fatores de risco cardiovascular em pessoas com síndrome de Down / Relationship between the consumption in fat saturated and cardiovascular risk factors in people with Down syndrome

Objetivo: Avaliar a relação entre o consumo de gordura saturada e o risco cardiovascular em pessoas com síndrome de Down. Estudo transversal, realizado em 33 crianças e adolescentes com síndrome de Down atendidos no Centro Integrado de Educação Especial, de ambos os sexos, com idade entre 3 e 14 anos. Método: Para determinação do estado nutricional, foram utilizadas as curvas específicas. Na avaliação do consumo alimentar foi utilizado o recordatório 24 horas, analisado pelo software "Nutwin", versão 1.5. Para identificação do risco cardiovascular, foram realizadas medidas de circunferências da cintura e pescoço, índice de conicidade, além da pressão arterial. A análise estatística dos dados foi realizada por meio do SPSS v. 18.0, utilizando os testes t de Student, para comparar os valores médios, e a correlação de Pearson, para verificar associação entre as variáveis. Resultados: O indicador P/I revelou excesso de peso para 19,04% do sexo feminino, enquanto que o consumo de gordura saturada esteve inadequado para ambos os sexos, sendo 75% e 85,71%, para meninos e meninas, respectivamente. Quanto ao risco cardiovascular, os valores médios e desvio padrão encontrados para o índice de conicidade foram de 1,02±0,47 e 1,24±0,34 para meninos e meninas, respectivamente, com diferença significativa entre os sexos (p<0,05). Conclusão: Os participantes apresentam risco cardiovascular e a inadequação no consumo de gordura saturada contribui para essa condição.(AU)

Objectives: To evaluate the relationship between the consumption of saturated fat and cardiovascular risk in people with Down syndrome. Cross-sectional study conducted in 33 children and adolescents with Down syndrome seen at Centro Integrado de Educação Especial, of both sexes, aged between 3 and 14 years. Methods: To determine the nutritional status we used the specific curves. In assessing the food intake was used the 24-hour recall, analyzed by software "Nutwin" 1.5 version. To identify cardiovascular risk, waist and neck circumferences, conicity index, as well as blood pressure were measured. Statistical analysis was performed using SPSS v. 18.0 using the t test Student to compare the mean values and the Pearson correlation to verify the association between variables. Results: The P / I indicator revealed excess weight to 19.04% female, while saturated fat intake was inadequate for both sexes, 75% and 85.71% for boys and girls, respectively. As the cardiovascular risk mean values and standard deviation found for conicity index were 1.02±0.47 and 1.24±0.34 for boys and girls, respectively, with a significant difference between the sexes (p<0.05). Conclusion: Participants have cardiovascular risk and inadequate in saturated fat consumption contributes to this condition.(AU)