The incidence risk of gynecological cancer by antipsychotic use: a meta-analysis of 50,402 patients.

BACKGROUND: Female gynecological cancers represent a serious public health problem, with 1,398,601 new diagnoses and 671,875 deaths per year worldwide. Antipsychotics are often used in psychiatric disorders, including schizophrenia, bipolar disorder, and major depression. It is estimated that the prescription of these drugs is linked to 1,800 deaths a year in the United States, but their association with cancer remains controversial. METHODS: We searched PubMed, Scopus, and Web of Science databases for studies reporting the correlation in the incidence risk of gynecological cancer by antipsychotic use. We used DerSimonian and Laird random-effect models to compute logit transformed odds ratio (OR) for the primary binary endpoint with 95% confidence interval (CI). Heterogeneity was assessed through effect size width along with I-squared and Tau-squared statistics. Review Manager 5.4.1. was used for statistical analyses. A p-value of < 0.05 denoted statistically significant. RESULTS: 50,402 patients were included, of whom 778 (1,54%) took antipsychotic medication for at least 1 year. 1,086 (2,15%) with ovarian cancer and 49,316 (97,85%) with endometrial cancer. Antipsychotic use (OR 1.50; 1.06 to 2.13 95% CI; p-value 0.02), hypertension (OR 1.50; 95% CI 1.06 to 2.13; p-value < 0.01), nulliparity (OR 1.98; 95% CI 1.53 to 2.57; p-value < 0.01) and multiparity (OR 0.53; 95% CI 0.41 to 0.69; p-value < 0.01) showed significantly different distributions between groups of cancer and cancer-free patients. The primary endpoint of incidence risk of gynecological cancer by antipsychotic therapy showed a statistically significant difference (OR 1.67; 95% CI 1.02 to 2.73; p-value < 0.05) against the use of antipsychotic drugs. CONCLUSIONS: Our meta-analysis showed that the use of antipsychotic drugs increases the risk of gynecological cancers, particularly endometrial cancer. This result should be weighed against the potential effects of treatment for a balanced prescribing decision.

PD-1/PD-L1 inhibitors plus carboplatin and paclitaxel compared with carboplatin and paclitaxel in primary advanced or recurrent endometrial cancer: a systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: Paclitaxel and carboplatin is the standard chemotherapy for the treatment of advanced or recurrent endometrial cancer. However, the benefit of adding programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors to chemotherapy is still unclear. METHOD: We searched PubMed, Scopus, Cochrane, and Web of Science databases for randomized controlled trials that investigated PD-1/PD-L1 inhibitors plus carboplatin and paclitaxel compared with carboplatin and paclitaxel in primary advanced or recurrent endometrial cancer. We computed hazard ratios (HRs) or risk ratios (RRs) for binary endpoints, with 95% confidence intervals (CIs). We used DerSimonian and Laird random-effect models for all endpoints. Heterogeneity was assessed using I2 statistics. R, version 4.2.3, was used for statistical analyses. RESULTS: A total of three studies and 1,431 patients were included. Compared with carboplatin plus paclitaxel-based chemotherapy, progression-free survival (PFS) rate (HR 0.32; 95% CI 0.23-0.44; p < 0.001) and overall survival (OS) at 30 months (RR 3.13; 95% CI 1.26-7.78; p = 0.01) were significant in favor of the PD-1/PD-L1 inhibitors plus carboplatin and paclitaxel group in the mismatch repair-deficient subgroup. However, there were no significant differences in the mismatch repair-proficient subgroup for PFS (HR 0.74; 95% CI 0.50-1.08; p = 0.117) or OS at 30 months (RR 2.24; 95% CI 0.79-6.39; p = 0.13). CONCLUSION: Immunotherapy plus carboplatin-paclitaxel increased significantly PFS and OS among patients with advanced or recurrent endometrial cancer, with a significant benefit in the mismatch repair-deficient and high microsatellite instability population.

Mesenchymal-Epithelial Transition Kinase Inhibitor Therapy in Patients with Advanced Papillary Renal-Cell Carcinoma: A Systematic Review and Meta-Analysis.

Papillary subtypes of renal-cell carcinoma (pRCC) represent 10-15% of the cases and commonly have MET alterations. This systematic review and single-arm meta-analysis evaluated MET inhibitor therapy (METi) efficacy and safety in adults with confirmed advanced pRCC. The search strategy included PubMed, Web-of-science, Cochrane, and Scopus. We used the DerSimonian/Laird random effect model for all analyses; p-value < 5% was considered significant, and heterogeneity was assessed with I2. Three clinical trials and six cohort studies were included with 504 patients; 31% were MET-driven. Our pooled analysis demonstrated an objective response rate (ORR) in MET-driven, MET-independent, and overall patients of: 36% (95%CI: 10-62), 0% (95%CI: 0-3), and 21% (95%CI: 1-41), respectively. One-year disease control and progression-free survival rates were, respectively, 70% (95%CI: 52-88) and 15% (95%CI: 10-20). Twelve- and twenty-four-month survival rates were, respectively, 43% (95%CI: 23-64) and 10% (95%CI: 0-30). The prevalence of adverse events of any grade and grades 3-5 were 96% (95%CI: 91-100) and 44% (95%CI: 37-50), respectively. We suggest METi has anti-tumor activity and is tolerable in patients with advanced pRCC.

Influence of Genetic Variations in miRNA and Genes Encoding Proteins in the miRNA Synthesis Complex on Toxicity of the Treatment of Pediatric B-Cell ALL in the Brazilian Amazon.

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.

Association between SNPs in microRNAs and microRNAs-Machinery Genes with Susceptibility of Leprosy in the Amazon Population.

Leprosy is a chronic neurodermatological disease caused by the bacillus Mycobacterium leprae. Recent studies show that SNPs in genes related to miRNAs have been associated with several diseases in different populations. This study aimed to evaluate the association of twenty-five SNPs in genes encoding miRNAs related to biological processes and immune response with susceptibility to leprosy and its polar forms paucibacillary and multibacillary in the Brazilian Amazon. A total of 114 leprosy patients and 71 household contacts were included in this study. Genotyping was performed using TaqMan Open Array Genotyping. Ancestry-informative markers were used to estimate individual proportions of case and control groups. The SNP rs2505901 (pre-miR938) was associated with protection against the development of paucibacillary leprosy, while the SNPs rs639174 (DROSHA), rs636832 (AGO1), and rs4143815 (miR570) were associated with protection against the development of multibacillary leprosy. In contrast, the SNPs rs10739971 (pri-let-7a1), rs12904 (miR200C), and rs2168518 (miR4513) are associated with the development of the paucibacillary leprosy. The rs10739971 (pri-let-7a1) polymorphism was associated with the development of leprosy, while rs2910164 (miR146A) and rs10035440 (DROSHA) was significantly associated with an increased risk of developing multibacillary leprosy.

Traps and trumps from adjacent-to-tumor samples in gastric cancer research.

The search for cancer biomarkers is frequently based on comparisons between tumors and adjacent-to-tumor samples. However, even after histological confirmation of been free of cancer cells, these adjacent-to-tumor samples might harbor molecular alterations which are not sufficient to cause them to look like cancer, but can differentiate these cells from normal cells. When comparing them, potential biomarkers are missed, and mainly the opportunity of finding initial aberrations presents in both tumors and adjacent samples, but not in true normal samples from non-cancer patients, resulting in misinterpretations about the carcinogenic process. Nevertheless, collecting adjacent-to-tumor samples brings trumps to be explored. The addition of samples from non-cancer patients opens an opportunity to increase the finds of the molecular cascade of events in the carcinogenic process. Differences between normal samples and adjacent samples might represent the first steps of the carcinogenic process. Adding samples of non-cancer patients to the analysis of molecular alterations relevant to the carcinogenic process opens a new window of opportunities to the discovery of cancer biomarkers and molecular targets.

Ancestry informative markers and selected single nucleotide polymorphisms in immunoregulatory genes on preterm labor and preterm premature rupture of membranes: a case control study.

BACKGROUND: A genetic predisposition to Preterm Labor (PTL) and Preterm Premature Rupture of Membranes (PPROM) has been suggested; however the relevance of polymorphisms and ancestry to susceptibility to PTL and PPROM in different populations remains unclear. The aim of this study was to evaluate the contribution of maternal and fetal SNPs in the IL1B, IL6, IL6R, TNFA, TNFR, IL10, TLR2, TLR4, MMP9, TIMP1 and TIMP2 genes and the influence of ancestry background in the susceptibility to PTL or PPROM in Brazilian women. METHODS: Case-control study conducted at a tertiary hospital in São Paulo State, Brazil. We included women with PTL or PPROM and their babies (PTL: 136 women and 88 babies; PPROM: 65 women and 44 babies). Control group included 402 mother-babies pairs of term deliveries. Oral swabs were collected for identification of AIMs by fragment analysis and SNPs by Taqman® SNP Genotyping Assays and PCR. Linkage Disequilibrium and Hardy-Weinberg proportions were evaluated using Genepop 3.4. Haplotypes were inferred using the PHASE algorithm. Allele, genotype and haplotype frequencies were compared by Fisher's exact test or χ (2) and Odds Ratio. Logistic regression was performed. Clinical and sociodemographic data were analyzed by Fisher's exact test and Mann-Whitney. RESULTS: PTL was associated with European ancestry and smoking while African ancestry was protective. The fetal alleles IL10-592C (rs800872) and IL10-819C (rs1800871) were also associated with PTL and the maternal haplotype TNFA-308G-238A was protective. Maternal presence of IL10-1082G (rs1800896) and TLR2A (rs4696480) alleles increased the risk for PPROM while TNFA-238A (rs361525) was protective. Family history of PTL/PPROM was higher in cases, and time to delivery was influenced by IL1B-31T (rs1143627) and TLR4-299G (rs4986790). CONCLUSION: There is an association between European ancestry and smoking and PTL in our Brazilian population sample. The presence of maternal or fetal alleles that modify the inflammatory response increase the susceptibility to PTL and PPROM. The family history of PTL/PPROM reinforces a role for genetic polymorphisms in susceptibility to these outcomes.

Genomic Variants and Worldwide Epidemiology of Breast Cancer: A Genome-Wide Association Studies Correlation Analysis.

Breast cancer (BCa) is the most common cancer and leading cause of cancer death among women globally. This can be explained by the genetic factor of this disease. This article aims to correlate the epidemiological data, worldwide incidence, and mortality of BCa with the Single-Nucleotide Polymorphisms (SNPs) associated with the susceptibility and severity in different populations. Two hundred and forty genetic variants associated with BCa susceptibility/severity were selected from the literature through Genome-Wide Association Studies (GWAS). The allele frequencies were obtained from the 1000 Genomes Project, and the epidemiological data were obtained from the World Health Organization (WHO). The BCa incidence, mortality rates, and allele frequencies of the variants were evaluated using Pearson's correlation. Our study demonstrated that 11 SNPs (rs3817578, rs4843437, rs3754934, rs61764370, rs780092, rs2290203, rs10411161, rs6001930, rs16886165, rs8051542 and rs4973768) were significantly correlated with the epidemiological data in different ethnic groups. Seven polymorphisms (rs3817578, rs3754934, rs780092, rs2290203, rs10411161, rs6001930 and rs16886165) were inversely correlated with the incidence rate and four polymorphisms (rs4843437, rs61764370, rs8051542 and rs4973768) were directly correlated with the incidence rate. African and South-East Asian populations have a lower risk of developing BCa when evaluated in terms of genetic factors since they possess variants characterized as protective, as their higher incidence is associated with a lower frequency of BCa cases. The genetic variants investigated here are likely to predispose individuals to BCa. The genetic study described here is promising for implementing personalized strategies to screen for breast cancer in diverse populations.

The Use of Honey for Cicatrization and Pain Control of Obstetric Wounds: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: Several studies point to antibacterial properties and beneficial effects of honey on scar tissue formation, which is a low-cost and easy-to-use option. This study aimed to compare honey versus a placebo for cicatrization and pain control of obstetric wounds, and determine if one is superior to the other, in terms of efficacy, through a meta-analysis. METHODS: We searched PubMed, Scopus, Cochrane Central Register of Controlled Trials, and Web of Science. Two independent investigators identified randomized controlled trials (RCTs) comparing honey and a placebo for obstetric wounds. The primary outcomes were wound healing and pain control. RESULTS: Five randomized controlled trials and 353 patients were included, of whom, 177 (50.1%) were treated with honey. Differences were not found in the final wound healing between the honey and placebo groups (MD -0.34; 95% CI -1.13, 0.44; p = 0.39); however, there was a decrease in pain levels in the middle of the treatment (SMD -0.54; 95% CI 0.83 to 0.25, p = 0.03), reduction in the use of pain medication (ORR 0.26; 95% CI 0.08, 0.86; p = 0.03), increase in personal satisfaction in women who underwent the intervention (ORR 0.81; 95% CI 0.65, 0.98), and reduction in complications. CONCLUSION: According to the study results, honey treatments showed greater efficiency and provided benefits to the patients by accelerating wound healing and decreasing reported pain.

Genomic investigation on genes related to mercury metabolism in Amazonian indigenous populations.

Studies have identified elevated levels of mercury in Amazonian Indigenous individuals, highlighting them as one of the most exposed to risks. In the unique context of the Brazilian Indigenous population, it is crucial to identify genetic variants with clinical significance to better understand vulnerability to mercury and its adverse effects. Currently, there is a lack of research on the broader genomic profile of Indigenous people, particularly those from the Amazon region, concerning mercury contamination. Therefore, the aim of this study was to assess the genomic profile related to the processes of mercury absorption, distribution, metabolism, and excretion in 64 Indigenous individuals from the Brazilian Amazon. We aimed to determine whether these individuals exhibit a higher susceptibility to mercury exposure. Our study identified three high-impact variants (GSTA1 rs1051775, GSTM1 rs1183423000, and rs1241704212), with the latter two showing a higher frequency in the study population compared to global populations. Additionally, we discovered seven new variants with modifier impact and a genomic profile different from the worldwide populations. These genetic variants may predispose the study population to more harmful mercury exposure compared to global populations. As the first study to analyze broader genomics of mercury metabolism pathways in Brazilian Amazonian Amerindians, we emphasize that our research aims to contribute to public policies by utilizing genomic investigation as a method to identify populations with a heightened susceptibility to mercury exposure.

Cyclin-Dependent Kinase 4/6 Inhibitors Plus Endocrine Therapy versus Endocrine Therapy Alone for HR-Positive, HER-2-Negative Early Breast Cancer: Meta-Analysis of Phase III Randomized Clinical Trials.

BACKGROUND: Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors are approved for advanced breast cancer combined with endocrine therapy (ET). The efficacy of CDK4/6 inhibitors plus ET in hormone estrogen-positive, human epidermal growth factor 2-negative (HR+/HER2-) early-stage breast cancer (esBC) is still to be confirmed. METHODS: We performed a systematic review and a meta-analysis to investigate the efficacy of CDK4/6i plus ET in esBC. Main outcomes included invasive disease-free survival (iDFS), distant relapse-free survival (DRFS), and overall survival (OS). We included only phase III randomized controlled trials. We used RStudio version 4.2.3, and we considered p < 0.05 to be statistically significant. RESULTS: Four studies were selected, including 14,168 patients, of which 7089 were treated with CDK4/6i plus ET and 7079 received ET monotherapy. Regarding patient characteristics, 6828 (48.2%) were premenopausal. Compared with ET alone, iDFS rates (HR 0.81; 95% CI: 0.67, 0.98; p = 0.034) were significantly in favor of CDK4/6 inhibitors plus ET. However, there were no significant differences in DRFS (HR 0.79; 95% CI: 0.58, 1.07; p = 0.132) nor OS (HR 0.96; 95% CI: 0.69, 1.35; p = 0.829). CONCLUSIONS: Our results show that the addition of CDK4/6 inhibitors is associated with a significant benefit for HR+/HER2- esBC patients in iDFS. More studies and longer follow-up are needed to assess overall survival benefits.

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.

Correlation between Genomic Variants and Worldwide COVID-19 Epidemiology.

COVID-19 is a systemic disease caused by the etiologic agent SARS-CoV-2, first reported in Hubei Province in Wuhan, China, in late 2019. The SARS-CoV-2 virus has evolved over time with distinct transmissibility subvariants from ancestral lineages. The clinical manifestations of the disease vary according to their severity and can range from asymptomatic to severe. Due to the rapid evolution to a pandemic, epidemiological studies have become essential to understand and effectively combat COVID-19, as the incidence and mortality of this disease vary between territories and populations. This study correlated epidemiological data on the incidence and mortality of COVID-19 with frequencies of important SNPs in GWAS studies associated with the susceptibility and mortality of this disease in different populations. Our results indicated significant correlations for 11 genetic variants (rs117169628, rs2547438, rs2271616, rs12610495, rs12046291, rs35705950, rs2176724, rs10774671, rs1073165, rs4804803 and rs7528026). Of these 11 variants, 7 (rs12046291, rs117169628, rs1073165, rs2547438, rs2271616, rs12610495 and rs35705950) were positively correlated with the incidence rate, these variants were more frequent in EUR populations, suggesting that this population is more susceptible to COVID-19. The rs2176724 variant was inversely related to incidence rates; therefore, the higher the frequency of the allele is, the lower the incidence rate. This variant was more frequent in the AFR population, which suggests a protective factor against SARS-CoV-2 infection in this population. The variants rs10774671, rs4804803, and rs7528026 showed a significant relationship with mortality rates. SNPs rs10774671 and rs4804803 were inversely related to mortality rates and are more frequently present in the AFR population. The rs7528026 variant, which is more frequent in the AMR population, was positively related to mortality rates. The study has the potential to identify and correlate the genetic profile with epidemiological data, identify populations that are more susceptible to severe forms of COVID-19, and relate them to incidence and mortality.

Molecular Profile of Important Genes for Radiogenomics in the Amazon Indigenous Population.

Radiotherapy is focused on the tumor but also reaches healthy tissues, causing toxicities that are possibly related to genomic factors. In this context, radiogenomics can help reduce the toxicity, increase the effectiveness of radiotherapy, and personalize treatment. It is important to consider the genomic profiles of populations not yet studied in radiogenomics, such as the indigenous Amazonian population. Thus, our objective was to analyze important genes for radiogenomics, such as ATM, TGFB1, RAD51, AREG, XRCC4, CDK1, MEG3, PRKCE, TANC1, and KDR, in indigenous people and draw a radiogenomic profile of this population. The NextSeq 500® platform was used for sequencing reactions; for differences in the allelic frequency between populations, Fisher's Exact Test was used. We identified 39 variants, 2 of which were high impact: 1 in KDR (rs41452948) and another in XRCC4 (rs1805377). We found four modifying variants not yet described in the literature in PRKCE. We did not find any variants in TANC1-an important gene for personalized medicine in radiotherapy-that were associated with toxicities in previous cohorts, configuring a protective factor for indigenous people. We identified four SNVs (rs664143, rs1801516, rs1870377, rs1800470) that were associated with toxicity in previous studies. Knowing the radiogenomic profile of indigenous people can help personalize their radiotherapy.

hTERT, MYC and TP53 deregulation in gastric preneoplastic lesions.

BACKGROUND: Gastric cancer is a serious public health problem in Northern Brazil and in the world due to its high incidence and mortality. Despite the severity of the disease, more research is needed to better understand the molecular events involved in this intestinal-type gastric carcinogenesis process. Since precancerous lesions precede intestinal-type gastric cancer, here, we evaluated the hTERT, MYC, and TP53 mRNA and protein expression, as well as TP33 copy number, in gastric preneoplastic lesions. METHODS: We evaluated 19 superficial gastritis, 18 atrophic gastritis, and 18 intestinal metaplasia from cancer-free individuals of Northern Brazil. Quantitative reverse transcription PCR was used to analyze the mRNA expression and immunohistochemical methods were used to assess protein immunoreactivity in tissue samples. The number of TP53 gene copies was investigated in gastric diseases by quantitative PCR. RESULTS: We observed hTERT, MYC, and p53 immunoreactivity only in intestinal metaplasia samples. The immunoreactivity of these proteins was strongly associated with each other. A significantly higher MYC mRNA expression was observed in intestinal metaplasia compared to gastritis samples. Loss of TP53 was also only detected in intestinal metaplasia specimens. CONCLUSIONS: We demonstrated that hTERT, MYC, and TP53 are deregulated in intestinal metaplasia of individuals from Northern Brazil and these alterations may facilitate tumor initiation.

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.

Genetic Variants of MicroRNA and DROSHA Genes in Association With the Risk of Tuberculosis in the Amazon Population.

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.

Characterization of PCLO Gene in Amazonian Native American Populations.

Genetic variations in PCLO have been associated with different pathologies in global literature, but there are no data regarding this gene in Native American populations. The Amazonian Native American populations have lower genetic diversity and are more different from other continental groups. We investigated 18 genetic variants in the PCLO gene in Amazonian indigenous and compared our results with the ones found in global populations, which were publicly available in the 1000 Genomes Project, gnmAD and ABraOM databases. The results demonstrated that the variants of the PCLO, especially rs17156844, rs550369696, rs61741659 and rs2877, have a significantly higher frequency in Amerindian populations in comparison with other continental populations. These data outline the singular genetic profile of the Native American population from the Brazilian Amazon region.

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.