Mucin (MUC) Family Influence on Acute Lymphoblastic Leukemia in Cancer and Non-Cancer Native American Populations from the Brazilian Amazon.

The mucin (MUC) family includes several genes aberrantly expressed in multiple carcinomas and mediates diverse pathways essentials for oncogenesis, in both solid and hematological malignancies. Acute Lymphoblastic Leukemia (ALL) can have its course influenced by genetic variants, and it seems more frequent in the Amerindian population, which has been understudied. Therefore, the present work aimed to investigate the MUC family exome in Amerindian individuals from the Brazilian Amazon, in a sample containing healthy Native Americans (NAMs) and indigenous subjects with ALL, comparing the frequency of polymorphisms between these two groups. The population was composed of 64 Amerindians from the Brazilian Amazon, from 12 different isolated tribes, five of whom were diagnosed with ALL. We analyzed 16 genes from the MUC family and found a total of 1858 variants. We compared the frequency of each variant in the ALL vs. NAM group, which led to 77 variants with a significant difference and, among these, we excluded those with a low impact, resulting in 63 variants, which were distributed in nine genes, concentrated especially in MUC 19 (n = 30) and MUC 3A (n = 18). Finally, 11 new variants were found in the NAM population. This is the first work with a sample of native Americans with cancer, a population which is susceptible to ALL, but remains understudied. The MUC family seems to have an influence on the development of ALL in the Amerindian population and especially MUC19 and MUC3A are shown as possible hotspots. In addition, the 11 new variants found point to the need to have their clinical impact analyzed.

Correlation between Genomic Variants and Worldwide Epidemiology of Prostate Cancer.

Prostate cancer (PCa) incidence and mortality vary across territories and populations. This can be explained by the genetic factor of this disease. This article aims to correlate the epidemiological data, worldwide incidence, and mortality of PCa with single-nucleotide polymorphisms (SNPs) associated with the susceptibility and severity of this neoplasm in different populations. Eighty-four genetic variants associated with prostate cancer susceptibility were selected from the literature through genome association studies (GWAS). Allele frequencies were obtained from the 1000 Genomes Project, and epidemiological data were obtained from Surveillance, Epidemiology, and End Results (SEER). The PCa incidence, mortality rates, and allele frequencies of variants were evaluated by Pearson's correlation. Our study demonstrated that 12 SNPs (rs2961144, rs1048169, rs7000448, rs4430796, rs2066827, rs12500426, rs6983267, rs11649743, rs2075110, rs114798100, rs855723, and rs2075109) were correlated with epidemiological data in different ethnic groups. Ten SNPs (rs2961144, rs1048169, rs7000448, rs4430796, rs2066827, rs12500426, rs11649743, rs2075110, rs114798100, and rs2075109) were positively correlated with the mortality rate. Seven SNPs (rs1048169, rs2961144, rs7000448, rs4430796, rs2066827, rs12500426, and rs114798100) were positively correlated with incidence. Positive correlations of incidence and mortality rates were more frequent in the African population. The genetic variants investigated here are likely to predispose to PCa and could play a role in its progression and aggressiveness. This genetic study demonstrated here is promising for implementing personalized strategies to screen for prostate cancer in diverse populations.

Peripheral arterial disease progression and ankle brachial index: a cohort study with newly diagnosed patients with type 2 diabetes.

BACKGROUND: Little is known about the evolution of peripheral arterial disease (PAD) since diagnosis and its association with glycemic and lipid control in patients with Type 2 Diabetes Mellitus (T2DM). OBJECTIVE: Evaluate the actual criteria to start screening PAD with ankle-brachial index (ABI) in T2DM patients and assess its progression and relationship with glycemic and lipid control since diagnosis. METHODS: We performed a 3-year prospective cohort study with two groups: group 1 (978 individuals with T2DM undergoing drug treatment) and group 2 [221 newly diagnosed drug-naive (< 3 months) patients with T2DM]. PAD diagnosis was by ABI ≤ 0.90, regardless any symptoms. RESULTS: As expected, abnormal ABI prevalence was higher in group 1 vs. Group 2 (87% vs. 60%, p < 0.001). However, abnormal ABI prevalence did not differ between patients over and under 50 years in both groups. Our drug-naive group stabilizes ABI (0.9 ± 0.1 vs 0.9 ± 0.1, p = NS) and improved glycemic and lipid control during follow-up [glycated hemoglobin (HbA1c) = 8.9 ± 2.1 vs 8.4 ± 2.3%, p < 0.05; LDL = 132 ± 45 vs 113 ± 38 mg/dL, p < 0.01, respectively]. When compared, patients who evolved with normalization or maintained normal ABI levels at the end [Group A, N = 60 (42%)] with those who decreased ABI to abnormal levels (ABI basal 1.0 ± 0.1 vs final 0.85 ± 0.1, p < 0.001) [Group B, N = 26 (18%)], an improvement in HbA1c (9 ± 2 vs 8 ± 2%, p < 0.05) and a correlation between the final HbA1c with ABI (r = - 0.3, p = 0.01) was found only in the first. In addition, a correlation was found between albuminuria variation and ABI solely in group A (r = - 0.3; p < 0.05). CONCLUSION: Our study suggests that ABI should be measured at diagnosis in T2DM patients, indicating that current criteria to select patients to screen PAD with ABI must be simplified. An improvement in albuminuria and glycemic and lipid control could be related with ABI normalization in newly diagnosed T2DM drug-naive patients.

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.

Association of Soy and Exclusive Breastfeeding With Central Precocious Puberty: A Case-Control Study.

Introduction: While soy is suggested as a possible risk factor, exclusive breastfeeding (EBF) has a likely protective effect in precocious puberty. Our aim was to evaluate the association between both of these variables with central precocious puberty (CPP). Methods: We performed a retrospective, case-control study. A total of 161 girls were divided into two groups: 84 patients diagnosed with CPP composed the case group and 77 patients without the diagnosis of CPP (had gone through normal onset of puberty) were the control group. Results: Our control group had a higher presence of EBF >6 months, which was an important protective factor for CPP (OR: 0.5; IC 95%: 0.3-0.9, p = 0.05) and also correlated negatively with the presence of it (r = -0.2; p < 0.05). Oppositely, the use of soy was significantly higher in the CPP group, (OR: 3.8; IC 95%: 1.5-6, p < 0.05) and positively correlating (r = 0.2; p < 0.01) with the presence of CPP. Duration of soy intake (years) correlated with bone age (r = 0.415; p < 0.05). A logistic regression was performed to evaluate the effects of EBF duration and soy on CPP. The model was significant (x² (2) = 20,715, p = <0.001) and explained 12.2% (Nagelkerke R2) of the variance, correctly classifying 62.5% of cases. EBF was associated with a reduction of likelihood of having CPP [OR = 0,187 (CI = 0.055-0,635); Wald = 7,222, p = 0.007], while soy intake increased the risk [OR = 3.505 (CI) = 1,688-7,279, Wald = 11,319, p = 0.001]. Conclusion: Our data found the use of soy was associated with CPP. Additionally, EBF was pointed as a protective factor. However, future prospective studies are needed to clarify this issue.