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.

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.

Molecular Profile of Variants Potentially Associated with Severe Forms of COVID-19 in Amazonian Indigenous Populations.

Coronavirus disease 2019 (COVID-19) is an infection caused by SARS-CoV-2. Genome-wide association studies (GWASs) have suggested a strong association of genetic factors with the severity of the disease. However, many of these studies have been completed in European populations, and little is known about the genetic variability of indigenous peoples' underlying infection by SARS-CoV-2. The objective of the study is to investigate genetic variants present in the genes AQP3, ARHGAP27, ELF5L, IFNAR2, LIMD1, OAS1 and UPK1A, selected due to their association with the severity of COVID-19, in a sample of indigenous people from the Brazilian Amazon in order to describe potential new and already studied variants. We performed the complete sequencing of the exome of 64 healthy indigenous people from the Brazilian Amazon. The allele frequency data of the population were compared with data from other continental populations. A total of 66 variants present in the seven genes studied were identified, including a variant with a high impact on the ARHGAP27 gene (rs201721078) and three new variants located in the Amazon Indigenous populations (INDG) present in the AQP3, IFNAR2 and LIMD1 genes, with low, moderate and modifier impact, respectively.

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.

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.

Screening for Mutations in Hereditary Cancer Susceptibility Genes in a Region with High Endogamy in Brazil.

Introduction Cancer is a multifactorial disease dependent on the influence of genetic and environmental factors. About 10% of cancers are associated with germline mutations, which predispose to a higher risk of developing cancer. Currently, the use of panels that identify susceptibility and/or association genes cancer has been increasingly used, both in clinical practice and in scientific research. Objective To investigate genetic mutations in patients with a profile for hereditary cancer in individuals from a region of northeast Brazil, where there is a high frequency of endogenous and consanguineous marriages. Methods A set of 17 genes ( BRCA1 , BRCA2 , APC , TP53 , PTEN , RET , VHL , RB1 , CDKN2 , CDH1 , CHEK2 , MLH1 , MSH2 , MSH6 , MUTYH , XPA , and XPC ) associated with cancer and hereditary syndromes were analyzed. Fifteen patients with a hereditary cancer profile were evaluated. Results The pathogenic variant found was c.1187G > A (p.Gly396Asp), rs36053993 in the MUTYH gene in a male patient diagnosed with melanoma at the age of 43 years and a family history for this tumor. This gene encodes an important enzyme related to DNA repair and has been associated with other types of cancer, this is the first report of an association with melanoma, the biological plausibility of this association is given once the MUTYH protein is expressed in the skin tissue and is responsible for repairing damage caused, for example, by sun exposure. Conclusion The results of this study suggest that this mutation may be important for the hereditary predisposition to melanoma, but a broader investigation of this mutation is needed.

ncRNAs: an unexplored cellular defense mechanism in leprosy.

Leprosy is an infectious disease primarily caused by the obligate intracellular parasite Mycobacterium leprae. Although it has been considered eradicated in many countries, leprosy continues to be a health issue in developing nations. Besides the social stigma associated with it, individuals affected by leprosy may experience nerve damage leading to physical disabilities if the disease is not properly treated or early diagnosed. Leprosy is recognized as a complex disease wherein socioenvironmental factors, immune response, and host genetics interact to contribute to its development. Recently, a new field of study called epigenetics has emerged, revealing that the immune response and other mechanisms related to infectious diseases can be influenced by noncoding RNAs. This review aims to summarize the significant advancements concerning non-coding RNAs in leprosy, discussing the key perspectives on this novel approach to comprehending the pathophysiology of the disease and identifying molecular markers. In our view, investigations on non-coding RNAs in leprosy hold promise and warrant increased attention from researches in this field.

Variants of IFNL4 Gene in Amazonian and Northern Brazilian Populations.

Since the discovery of the polymorphic nature of the IFNL4 gene, its variants have been investigated and associated with several viral diseases, with an emphasis on hepatitis C. However, the impacts of these variants on mixed-race and native populations in the northern region of Brazil are scarce. We investigated three variants of the IFNL4 gene in populations from this location, which were among the 14 most frequent variants in worldwide populations, and compared the frequencies obtained to populational data from the 1000 Genomes Project, gnomAD and ABraOM databases. Our results demonstrate that mixed-race and native populations from the northern region of Brazil present frequencies like those of European and Asian groups for the rs74597329 and rs11322783 variants, and like all populations presented for the rs4803221 variant. These data reinforce the role of world populations in shaping the genetic profile of Brazilian populations, indicate patterns of illness according to the expressed genotype, and infer an individual predisposition to certain diseases.

Breast Cancer: Clinical-Epidemiological Profile and Toxicities of Women Receiving Treatment with Taxanes in the 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.

Molecular Profile of Variants in CDH1, TP53, PSCA, PRKAA1, and TTN Genes Related to Gastric Cancer Susceptibility in Amazonian Indigenous Populations.

Gastric Cancer is a disease associated with environmental and genetic changes, becoming one of the most prevalent cancers around the world and with a high incidence in Brazil. However, despite being a highly studied neoplastic type, few efforts are aimed at populations with a unique background and genetic profile, such as the indigenous peoples of the Brazilian Amazon. Our study characterized the molecular profile of five genes associated with the risk of developing gastric cancer by sequencing the complete exome of 64 indigenous individuals belonging to 12 different indigenous populations in the Amazon. The analysis of the five genes found a total of 207 variants, of which 15 are new in our indigenous population, and among these are two with predicted high impact, present in the TTN and CDH1 genes. In addition, at least 20 variants showed a significant difference in the indigenous population in comparison with other world populations, and three are already associatively related to some type of cancer. Our study reaffirms the unique genetic profile of the indigenous population of the Brazilian Amazon and allows us to contribute to the conception of early diagnosis of complex diseases such as cancer, improving the quality of life of individuals potentially suffering from the disease.

Epidemiological-molecular profile of variants associated with type 2 diabetes mellitus in indigenous populations from the Brazilian Amazon.

AIMS: While lifestyle factors are strongly associated with Type 2 diabetes (T2DM), genetic characteristics also play a role. However, much of the research on T2DM genetics focuses on European and Asian populations, leaving underrepresented groups, such as indigenous populations with high diabetes prevalence, understudied. METHODS: We characterized the molecular profile of 10 genes involved in T2DM risk through complete exome sequencing of 64 indigenous individuals belonging to 12 different Amazonian ethnic groups. RESULTS: The analysis revealed 157 variants, including four exclusive variants in the indigenous population located in the NOTCH2 and WFS1 genes with a modifier or moderate impact on protein effectiveness. Furthermore, a high impact variant in NOTCH2 was also found. Additionally, the frequency of 10 variants in the indigenous group showed significant differences when compared to other global populations that were evaluated. CONCLUSION: Our study identified 4 novel variants associated with T2DM in the NOTCH2 and WFS1 genes in the Amazonian indigenous populations we studied. In addition, a variant with a high predicted impact in NOTCH2 was also observed. These findings represent a valuable starting point for conducting further association and functional studies, which could help to improve our understanding of the unique characteristics of this population.

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.

Impact of pri-let-7a-1 rs10739971 for Gastric Cancer Predisposition in an Amazon Region.

Gastric cancer (GC) is the fifth most common type of cancer and the fourth leading cause of cancer death. In Brazil, GC has a high incidence and mortality rates, and it is highly variable by region. The Amazon region has significant rising rates among all Brazil regions. Only very few studies have evaluated the association between genetic variants and the risk of gastric cancer in the Brazilian Amazon population. Therefore, this study aimed to investigate associations between single nucleotide polymorphisms of miRNA processing genes and the risk for GC in this population. Potentially functional single nucleotide polymorphisms from miRNA processing genes were genotyped in 159 cases and 193 healthy controls by QuantStudio Real Time PCR. According to our findings, the genotype GG of the variant rs10739971 presents a lower risk to the development of GC in comparison to the remaining genotypes (p = 0.000016; OR = 0.055; 95% CI = 0.015-0.206). This is the first study to report the association of pri-let-7a-1 rs10739971 with GC in the Brazilian Amazon population, which is a highly mixed population with a unique genetic constitution that is different from other populations that are studied in the vast majority of scientific research.

Association between Polymorphism of Genes IL-1A, NFKB1, PAR1, TP53, and UCP2 and Susceptibility to Non-Small Cell Lung Cancer in the Brazilian Amazon.

Non-small cell lung cancer (NSCLC) accounts for the vast majority of cases of lung neoplasms. It is formed in multiple stages, with interactions between environmental risk factors and individual genetic susceptibility and with genes involved in the immune and inflammatory response paths, cell or genome stability, and metabolism, among others. Our objective was to evaluate the association between five genetic variants (IL-1A, NFKB1, PAR1, TP53, and UCP2) and the development of NSCLC in the Brazilian Amazon. The study included 263 individuals with and without lung cancer. The samples were analyzed for the genetic variants of NFKB1 (rs28362491), PAR1 (rs11267092), TP53 (rs17878362), IL-1A (rs3783553), and UCP2 (INDEL 45-bp), which were genotyped in PCR, followed by an analysis of the fragments, in which we applied a previously developed set of informative ancestral markers. We used a logistic regression model to identify differences in the allele and the genotypic frequencies among individuals and their association with NSCLC. The variables of gender, age, and smoking were controlled in the multivariate analysis to prevent confusion by association. The individuals that were homozygous for the Del/Del of polymorphism NFKB1 (rs28362491) (p = 0.018; OR = 0.332) demonstrate a significant association with NSCLC, which was similar to that observed in the variants of PAR1 (rs11267092) (p = 0.023; OR = 0.471) and TP53 (rs17878362) (p = 0.041; OR = 0.510). Moreover, the individuals with the Ins/Ins genotype of polymorphism IL-1A (rs3783553) demonstrated greater risk for NSCLC (p = 0.033; OR = 2.002), as did the volunteers with the Del/Del of UCP2 (INDEL 45-bp) (p = 0.031; OR = 2.031). The five polymorphisms investigated can contribute towards NSCLC susceptibility in the population of the Brazilian Amazon.

Asymptomatic Leishmania infection in humans: A systematic review.

BACKGROUND: Leishmaniasis is a highly prevalent neglected tropical disease. It mainly presents as two forms: cutaneous and visceral leishmaniasis, the latter being the most severe form. However, asymptomatic cases of Leishmania infection result in an increase in the underreporting and transmission of the protozoan OBJECTIVES: In this study, articles on the incidence of asymptomatic Leishmania infection were systematically reviewed. METHODS: The publications identified in the Medline/PubMed and Science Direct databases included 4568 articles. Inclusion, exclusion, and eligibility criterion analysis resulted in 83 articles being retained. These studies were mostly performed in Brazil (n = 26) and India (n = 15). RESULTS: Several detection techniques have been used for diagnosis. Among the species found were L. infantum and L. donovani, which result in visceral leishmaniasis, and L. amazonensis, L. braziliensis, and L. panamensis. The incidence rates varied between the analyzed locations, largely due to sampling and the presence or absence of endemism in the regions. The largest populations analyzed were in two studies performed in India and Nepal. One of these studies evaluated 32,529 people and the incidence rate was 8.3% (n = 2702), while the other study evaluated 21,267 people and the incidence rate was 1.76% (n = 375). Only 14.28% of the studies investigated leishmaniasis in blood donors. Preexisting diseases have also been reported. CONCLUSION: The findings of this systematic review present the incidence of cases of asymptomatic Leishmania infection worldwide, in addition to detailing the studies and offering information for researchers and health authorities to seek alternatives to reduce the number of leishmaniasis cases.

Potential anti-arthritic and analgesic properties of essential oil and viridiflorol obtained from Allophylus edulis leaves in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Viridiflorol was identified and isolated from the essential oil of Allophylus edulis leaves (EOAE). A. edulis was used as "tereré", which is a drink made by the infusion of herbs in cold water, to treat pain (toothache and headache). All anti-nociceptive (analgesic) and anti-arthritic properties of EOAE and viridiflorol have not been completely scientifically clarified. AIM OF THE STUDY: The aim of the present study was to investigate the analgesic (anti-hyperalgesic and anti-nociceptive) and anti-arthritic properties of EOAE and viridiflorol using in vivo models. MATERIALS AND METHODS: The oral administration (p.o.) of EOAE (30, 100 and 300 mg/kg), viridiflorol (30, 100 and 200 mg/kg), morphine (1 mg/kg, subcutaneous route (s.c.)) and the intraplantar (local) administration (i.pl.) of viridiflorol (100 µg/paw) were tested using formalin model in Swiss mice. EOAE (100 mg/kg, p.o.), viridiflorol (200 mg/kg, p.o.), and dexamethasone (1 mg/kg, s.c.) were tested by zymosan-articular inflammation and in open-field models. Viridiflorol (0.3, 20 and 200 µg/paw) was also tested in carrageenan model, and viridiflorol (200 µg/paw) was also tested in tumor necrosis factor-α (TNF-α), and dopamine (DOPA) models. RESULTS: The oral administration of EOAE (100 and 300 mg/kg, p.o.), viridiflorol (200 mg/kg, p.o.), morphine (1 mg/kg, s.c.) (MOR) and local administration of viridiflorol (100 µg/paw) significantly inhibited edema and nociception in formalin model. Oral treatments with EOAE and viridiflorol (200 mg/kg) did not cause motor impairment in the open field test since they did not reduce locomotor activity. EOAE, viridiflorol and dexamethasone significantly reduced mechanical hyperalgesia, edema, total leukocytes, polymorphonuclear cells, nitric oxide and protein exudation in the zymosan-induced articular inflammation model. The local administration of viridiflorol (200 µg/paw, i.pl.) significantly inhibited mechanical hyperalgesia and edema induced by carrageenan, TNF-α and DOPA. CONCLUSIONS: This study confirms the potential anti-arthritic, anti-nocicepttive and anti-hyperalgesic properties of EOAE and viridiflorol. These properties could explain, at least in part, the folk use of A. edulis against including pain (toothache and headache). Viridiflorol could be partially responsible for the EOAE anti-hyperalgesic, anti-nociceptive and anti-arthritic properties and its mechanism of action could involve the inhibition of TNF-α and DOPA pathways.

Geographical variation in the chemical composition, anti-inflammatory activity of the essential oil, micromorphology and histochemistry of Schinus terebinthifolia Raddi.

ETHNOPHARMACOLOGICAL RELEVANCE: Schinus terebinthifolia Raddi (Anacardiaceae) is rich in essential oil, distinguished by a predominance of monoterpenes and sesquiterpenes, it being widely used in traditional medicine for the treatment of inflammations. AIM OF STUDY: This study's objective was to investigate the chemical composition of the essential oil of S. terebinthifolia (EOST) collected in six states of Brazil, evaluate its anti-inflammatory effects in mice, and analyze the histochemistry and micromorphology of leaves and stems. MATERIALS AND METHODS: Aerial parts of S. terebinthifolia were collected in six states of Brazil, and the essential oil was extracted by hydrodistillation and analyzed by gas chromatography-mass spectrometry (GC-MS). The histochemistry and micromorphology of leaves and stems were performed using standard reagents, light and field emission scanning electron microscopy, beyond energy-dispersive X-ray spectroscopy. The EOST were evaluated for anti-inflammatory activity and hyperalgesia using the carrageenan-induced paw edema methodology. RESULTS: The EOST showed variation across the six states in its yield (0.40%-0.86%) and chemical composition: hydrocarbon monoterpenes (28.76%-47.73%), sesquiterpenes, (31.43%-41.76%), oxygenated monoterpenes (14.31%-19.57%), and oxygenated sesquiterpenes (4.87%-14.38%). Both α-pinene and limonene were predominant constituents of essential in five regions, except for one state where α-phellandrene and limonene were the dominant components. A comprehensive description of the leaf and stem micromorphology and histochemistry was performed. In the in vivo testing, all EOST samples exerted antiedematogenic and anti-hyperalgesic effects, when tested in a carrageenan-induced paw inflammation (mechanical and thermal hyperalgesia) model with oral doses of 30 mg/kg. CONCLUSION: Our results indicate that the EOST samples collected in six Brazilian states differed in their chemical composition but not their anti-inflammatory and antihyperalgesic effects, which was correlated with the synergistic effect of its components, collaborating the etnhopharmacologycal use of this plant due to its an anti-inflammatory effect. Also, micromorphology and histochemistry of leaves and stems presented in this study provide anatomical and microchemical information, which aids species identification.

Incidence of Hereditary Gastric Cancer May Be Much Higher than Reported.

Hereditary gastric cancers (HGCs) are supposed to be rare and difficult to identify. Nonetheless, many cases of young patients with gastric cancer (GC) fulfill the clinical criteria for considering this diagnosis but do not present the defined pathogenic mutations necessary to meet a formal diagnosis of HGC. Moreover, GC in young people is a challenging medical situation due to the usual aggressiveness of such cases and the potential risk for their relatives when related to a germline variant. Aiming to identify additional germline alterations that might contribute to the early onset of GC, a complete exome sequence of blood samples from 95 GC patients under 50 and 94 blood samples from non-cancer patients was performed and compared in this study. The number of identified germline mutations in GC patients was found to be much higher than that from individuals without a cancer diagnosis. Specifically, the number of high functional impact mutations, including those affecting genes involved in medical diseases, cancer hallmark genes, and DNA replication and repair processes, was much higher, strengthening the hypothesis of the potential causal role of such mutations in hereditary cancers. Conversely, classically related HGC mutations were not found and the number of mutations in genes in the CDH1 pathway was not found to be relevant among the young GC patients, reinforcing the hypothesis that existing alternative germline contributions favor the early onset of GC. The LILRB1 gene variants, absent in the world's cancer datasets but present in high frequencies among the studied GC patients, may represent essential cancer variants specific to the Amerindian ancestry's contributions. Identifying non-reported GC variants, potentially originating from under-studied populations, may pave the way for additional discoveries and translations to clinical interventions for GC management. The newly proposed approaches may reduce the discrepancy between clinically suspected and molecularly proven hereditary GC and shed light on similar inconsistencies among other cancer types. Additionally, the results of this study may support the development of new blood tests for evaluating cancer risk that can be used in clinical practice, helping physicians make decisions about strategies for surveillance and risk-reduction interventions.

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.

Treasures from trash in cancer research.

INTRODUCTION: Cancer research has significantly improved in recent years, primarily due to next-generation sequencing (NGS) technology. Consequently, an enormous amount of genomic and transcriptomic data has been generated. In most cases, the data needed for research goals are used, and unwanted reads are discarded. However, these eliminated data contain relevant information. Aiming to test this hypothesis, genomic and transcriptomic data were acquired from public datasets. MATERIALS AND METHODS: Metagenomic tools were used to explore genomic cancer data; additional annotations were used to explore differentially expressed ncRNAs from miRNA experiments, and variants in adjacent to tumor samples from RNA-seq experiments were also investigated. RESULTS: In all analyses, new data were obtained: from DNA-seq data, microbiome taxonomies were characterized with a similar performance of dedicated metagenomic research; from miRNA-seq data, additional differentially expressed sncRNAs were found; and in tumor and adjacent to tumor tissue data, somatic variants were found. CONCLUSIONS: These findings indicate that unexplored data from NGS experiments could help elucidate carcinogenesis and discover putative biomarkers with clinical applications. Further investigations should be considered for experimental design, providing opportunities to optimize data, saving time and resources while granting access to multiple genomic perspectives from the same sample and experimental run.