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1.
Med Sci (Basel) ; 12(2)2024 May 06.
Article in English | MEDLINE | ID: mdl-38804380

ABSTRACT

Gastric cancer has been demonstrating a reduction in the number of cases over the past decades, largely attributed to advancements in public health practices and increased accessibility to educational initiatives for the general population. Nevertheless, it persists as the third leading cause of mortality globally among both men and women. These fatalities are typically associated with delayed disease detection. The current study assessed the levels of homocysteine, vitamin B12, and folic acid as a means of establishing a screening biomarker profile that could be integrated into routine testing protocols to facilitate swift diagnosis of the illness. A total of 207 control subjects and 207 individuals with gastric cancer were scrutinized, with biochemical measurements conducted using chemiluminescence for homocysteine, folic acid, and vitamin B12. The two groups were matched based on age, tumor location, subtype, tumor classification, presence of Epstein-Barr Virus infection (EBV), and Helicobacter pylori (H. pylori). Significant statistical variances were identified in the mean levels of the triad of substances among cancer patients when compared to the control group for all corresponding variables. In conclusion, our study indicated that analyzing the triad of homocysteine, vitamin B12, and folic acid holds diagnostic value for gastric cancer and could potentially serve as an effective screening marker for this type of cancer in the future.


Subject(s)
Biomarkers, Tumor , Early Detection of Cancer , Folic Acid , Homocysteine , Stomach Neoplasms , Vitamin B 12 , Humans , Stomach Neoplasms/diagnosis , Vitamin B 12/blood , Folic Acid/blood , Homocysteine/blood , Male , Female , Middle Aged , Biomarkers, Tumor/blood , Aged , Adult , Case-Control Studies
2.
J Pers Med ; 14(5)2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38793065

ABSTRACT

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.

3.
Viruses ; 16(3)2024 02 26.
Article in English | MEDLINE | ID: mdl-38543725

ABSTRACT

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.


Subject(s)
COVID-19 , Humans , COVID-19/epidemiology , COVID-19/genetics , SARS-CoV-2/genetics , Genome-Wide Association Study , Gene Frequency , Indigenous Peoples/genetics , Intracellular Signaling Peptides and Proteins , LIM Domain Proteins
4.
J Pers Med ; 13(10)2023 Sep 30.
Article in English | MEDLINE | ID: mdl-37888069

ABSTRACT

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.

5.
Arq Bras Cir Dig ; 36: e1752, 2023.
Article in English | MEDLINE | ID: mdl-37729281

ABSTRACT

Metastatic gastric cancer traditionally hinders surgical treatment options, confining them to palliative procedures. The presence of metastases in these tumors is classified as M1, irrespective of their characteristics, quantity, or location. However, oligometastatic disease emerged as an intermediate state between localized and widely disseminated cancer. It exhibits diverse patterns based on metastatic disease extent, type, and location. Adequately addressing this distinctive metastatic state necessitates tailored strategies that surpass the realm of palliative care. Differentprimary tumor types present discernible scenarios of oligometastatic disease, including preferred sites of occurrence and chronological progression. Due to the novelty of this theme and the heterogeneity of the disease, uncertainties still exist, and the ability to provide confident guidelines is challenging. Currently, there are no effective predictors to determine the response and provide clear indications for surgical interventions and systemic treatments in oligometastatic disease. Treatment decisions are commonly based on apparent disease control by systemic therapies, with a short observation period and imaging assessments. Nonetheless, the inherent risk of misinterpretation remains a constant concern. The emergence of novel technologies and therapeutic modalities, such as immunotherapy, cellular therapy, and adoptive therapies, holds the potential to reshape the landscape of surgical treatment for the oligometastatic disease in gastric cancer, expanding the surgeon's role in this multidisciplinary approach. Prospective tools for patient selection in oligometastatic gastric cancer are being explored. Using non-invasive, cost-effective, widely available imaging techniques that provide real-time information may revolutionize medical practice, ensuring precision medicine accessibility, even in resource-constrained small healthcare facilities. Incorporating molecular classifications, liquid biopsies, and radiomic analysis in a complementary protocol will augment patient selection precision for surgical intervention in oligometastasis. Hopefully, these advancements will render surgeries unnecessary in many cases by providing highly effective alternative treatments.


Subject(s)
Stomach Neoplasms , Surgeons , Humans , Stomach Neoplasms/surgery , Palliative Care , Patient Selection
6.
J Pers Med ; 13(9)2023 Sep 08.
Article in English | MEDLINE | ID: mdl-37763132

ABSTRACT

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.

7.
Molecules ; 28(14)2023 Jul 22.
Article in English | MEDLINE | ID: mdl-37513459

ABSTRACT

Gastric cancer is one of the most frequent types of neoplasms worldwide, usually presenting as aggressive and difficult-to-manage tumors. The search for new structures with anticancer potential encompasses a vast research field in which natural products arise as promising alternatives. In this scenario, piperine, an alkaloid of the Piper species, has received attention due to its biological activity, including anticancer attributes. The present work proposes three heating-independent, reliable, low-cost, and selective methods for obtaining piperine from Piper nigrum L. (Black pepper). Electronic (SEM) and optical microscopies, X-ray diffraction, nuclear magnetic resonance spectroscopies (13C and 1H NMR), and optical spectroscopies (UV-Vis, photoluminescence, and FTIR) confirm the obtention of piperine crystals. The MTT assay reveals that the piperine samples exhibit good cytotoxic activity against primary and metastasis models of gastric cancer cell lines from the Brazilian Amazon. The samples showed selective cytotoxicity on the evaluated models, revealing higher effectiveness in cells bearing a higher degree of aggressiveness. Moreover, the investigated piperine crystals demonstrated the ability to act as a good cytotoxicity enhancer when combined with traditional chemotherapeutics (5-FU and GEM), allowing the drugs to achieve the same cytotoxic effect in cells employing lower concentrations. These results establish piperine as a promising molecule for therapy investigations in aggressive gastric cancer, both in its isolated form or as a bioenhancer.


Subject(s)
Alkaloids , Antineoplastic Agents , Piper nigrum , Stomach Neoplasms , Humans , Stomach Neoplasms/drug therapy , Alkaloids/chemistry , Benzodioxoles/chemistry , Piperidines/chemistry , Polyunsaturated Alkamides/chemistry , Piper nigrum/chemistry , Antineoplastic Agents/pharmacology
8.
Genes (Basel) ; 14(2)2023 02 09.
Article in English | MEDLINE | ID: mdl-36833380

ABSTRACT

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.


Subject(s)
MicroRNAs , Stomach Neoplasms , Humans , Genetic Predisposition to Disease , Genotype , MicroRNAs/genetics , Polymorphism, Single Nucleotide , Stomach Neoplasms/genetics
9.
ABCD (São Paulo, Online) ; 36: e1752, 2023. graf
Article in English | LILACS-Express | LILACS | ID: biblio-1513510

ABSTRACT

ABSTRACT Metastatic gastric cancer traditionally hinders surgical treatment options, confining them to palliative procedures. The presence of metastases in these tumors is classified as M1, irrespective of their characteristics, quantity, or location. However, oligometastatic disease emerged as an intermediate state between localized and widely disseminated cancer. It exhibits diverse patterns based on metastatic disease extent, type, and location. Adequately addressing this distinctive metastatic state necessitates tailored strategies that surpass the realm of palliative care. Differentprimary tumor types present discernible scenarios of oligometastatic disease, including preferred sites of occurrence and chronological progression. Due to the novelty of this theme and the heterogeneity of the disease, uncertainties still exist, and the ability to provide confident guidelines is challenging. Currently, there are no effective predictors to determine the response and provide clear indications for surgical interventions and systemic treatments in oligometastatic disease. Treatment decisions are commonly based on apparent disease control by systemic therapies, with a short observation period and imaging assessments. Nonetheless, the inherent risk of misinterpretation remains a constant concern. The emergence of novel technologies and therapeutic modalities, such as immunotherapy, cellular therapy, and adoptive therapies, holds the potential to reshape the landscape of surgical treatment for the oligometastatic disease in gastric cancer, expanding the surgeon's role in this multidisciplinary approach. Prospective tools for patient selection in oligometastatic gastric cancer are being explored. Using non-invasive, cost-effective, widely available imaging techniques that provide real-time information may revolutionize medical practice, ensuring precision medicine accessibility, even in resource-constrained small healthcare facilities. Incorporating molecular classifications, liquid biopsies, and radiomic analysis in a complementary protocol will augment patient selection precision for surgical intervention in oligometastasis. Hopefully, these advancements will render surgeries unnecessary in many cases by providing highly effective alternative treatments.


RESUMO O câncer gástrico metastático representa um desafio para o tratamento cirúrgico, restringindo-se a procedimentos paliativos. A presença de metástases nestes tumores é categorizada como estágio M1, independentemente das características, quantidade e localização. No entanto, a doença oligometastática surgiu como um estado intermediário entre o câncer localizado e o amplamente disseminado. A oligometastática apresenta diversos padrões com base na extensão, tipo e localização da doença metastática. Abordar adequadamente esse estado distintivo requer estratégias adaptadas que ultrapassem o escopo dos cuidados paliativos. Diferentes tipos de tumores primários exibem cenários distintos de oligometastática, incluindo locais preferenciais de ocorrência e progressão cronológica. Devido à novidade desse tema e à heterogeneidade da doença, ainda existem incertezas, e a capacidade de fornecer diretrizes seguras é limitada. Atualmente, não existem preditores eficazes para determinar a resposta e fornecer indicações claras para intervenções cirúrgicas e tratamentos sistêmicos em oligometastática. As decisões de tratamento geralmente se baseiam no controle aparente da doença por meio de terapias sistêmicas, com um curto período de observação e avaliação por imagem. No entanto, o risco inerente de interpretação incorreta continua sendo uma preocupação constante. A emergência de novas tecnologias e modalidades terapêuticas, como imunoterapia, terapia celular e terapias adotivas, tem o potencial de remodelar o panorama do tratamento cirúrgico da oligometastática no câncer gástrico, expandindo o papel do cirurgião nessa abordagem multidisciplinar. Ferramentas prospectivas para a seleção de pacientes com câncer gástrico oligometastático estão sendo exploradas. A utilização de técnicas de imagem não invasivas, rentáveis e amplamente disponíveis, que fornecem informações em tempo real, pode revolucionar a prática médica, garantindo a acessibilidade da medicina de precisão, mesmo em unidades de saúde com recursos limitados. A incorporação de classificações moleculares, biópsias líquidas e análises radiômicas em um protocolo complementar aumentará a precisão da seleção de pacientes para intervenção cirúrgica em oligometástases. Espera-se que esses avanços tornem as cirurgias desnecessárias em muitos casos, proporcionando tratamentos alternativos altamente eficazes.

10.
J Pers Med ; 12(12)2022 Dec 13.
Article in English | MEDLINE | ID: mdl-36556273

ABSTRACT

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.

11.
Genes (Basel) ; 13(10)2022 10 15.
Article in English | MEDLINE | ID: mdl-36292754

ABSTRACT

Native American populations from the Brazilian Amazon have a low genetic diversity and a different genetic profile when compared to people from other continents. Despite this, few studies have been conducted in this group, and there is no description of their genetic data in the various currently existent international databases. The characterization of the genomic profile of a population not only has an impact in studies of population genetics, but also helps to advance diagnostic and therapeutic response studies, leading to the optimization of clinical applicability. Genetic variations in DNA repair genes have been associated with the modulation of susceptibility to various pathologies, as well as in their prognosis and therapy. This is the first study to investigate DNA repair genes in Amerindians from the Brazilian Amazon region. We investigated 13 important DNA repair genes in the exome of 63 Native Americans, comparing our results with those found in 5 continental populations, whose data are available in the Genome Aggregation Database. Our results showed that 57 variants already described in literature were differentially distributed in the Amerindian populations in relation to the continental populations, 7 of which have significant clinical relevance. In addition, 9 new variants were described, suggesting that they are unique to these populations. Our study reinforces the understanding that the Amazonian Native American population presents a unique genetic profile, and our findings may collaborate with the creation of public policies that optimize the quality of life of these groups as well as the Brazilian population, which presents a high degree of interethnic mixing with Amerindian groups.


Subject(s)
Indians, South American , Quality of Life , Humans , Indians, South American/genetics , Molecular Epidemiology , Brazil/epidemiology , DNA Repair/genetics
12.
Curr Issues Mol Biol ; 44(2): 942-951, 2022 Feb 15.
Article in English | MEDLINE | ID: mdl-35723347

ABSTRACT

piRNAs are a class of noncoding RNAs that perform functions in epigenetic regulation and silencing of transposable elements, a mechanism conserved among most mammals. At present, there are more than 30,000 known piRNAs in humans, of which more than 80% are derived from intergenic regions, and approximately 20% are derived from the introns and exons of pre-mRNAs. It was observed that the expression of the piRNA profile is specific in several organs, suggesting that they play functional roles in different tissues. In addition, some studies suggest that changes in regions that encode piRNAs may have an impact on their function. To evaluate the conservation of these regions and explore the existence of a seed region, SNP and INDEL variant rates were investigated in several genomic regions and compared to piRNA region variant rates. Thus, data analysis, data collection, cleaning, treatment, and exploration were implemented using the R programming language with the help of the RStudio platform. We found that piRNA regions are highly conserved after considering INDELs and do not seem to present an identifiable seed region after considering SNPs and INDEL variants. These findings may contribute to future studies attempting to determine how polymorphisms in piRNA regions can impact diseases.

13.
J Pers Med ; 12(3)2022 Feb 28.
Article in English | MEDLINE | ID: mdl-35330370

ABSTRACT

Acute lymphoblastic leukemia (ALL) is the most common cancer during childhood, representing about 30-35% of cases. Its etiology is complex and not fully understood. ALL is influenced by genetic variants, and their frequencies (Fq) vary in different ethnic groups, which consequently could influence the epidemiology of this cancer worldwide. The aim of this study was to investigate the correlation between the genetic variants and their impacts on incidence (IC), mortality (MT), and prevalence (PV) rates of ALL in different world populations. METHODS: Sixty variants were selected from the literature with Genome Wide Association studies (GWAS). Information regarding allele Fq was selected from the 1000 Genomes platform. Epidemiological data were taken from the Global Burden of disease visualisations (GBD) Compare website. Statistical analyses were calculated in RStudio v.3.5.1 software. RESULTS: Four variants demonstrated significant results in correlations with epidemiological data for ALL. The PAX5 gene variant (rs2297105) had an indirect relationship with PV and IC of ALL, showing that an increased Fq of this variant is related to low rates of both. An increased Fq of rs915172 in EPB4IL2 gene was also correlated with a lower IC of ALL. The rs1048943 of the CYP1A1 gene and the rs3088440 polymorphism of the CDKN2A gene were shown to have a direct proportional relationship with MT rate, showing that an increased Fq of these variants correlates with a worse prognosis worldwide. CONCLUSION: Our study points out four important variants for understanding the IC, PV, and MT rates for ALL. The ascertainment of these data may help to choose molecular markers to investigate the susceptibility and prognosis of ALL.

14.
Genes (Basel) ; 13(2)2022 02 10.
Article in English | MEDLINE | ID: mdl-35205374

ABSTRACT

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm derived from the balanced reciprocal translocation of chromosomes 9 and 22 t (9q34 and 22q11), which leads to the formation of the Philadelphia chromosome and fusion of the BCR-ABL genes. The first-line treatment for CML is imatinib, a tyrosine kinase inhibitor that acts on the BCR-ABL protein. However, even though it is a target-specific drug, about 25% of patients do not respond to this treatment. The resistance mechanisms involved in this process have been investigated and studies have shown that germinal alterations can influence this mechanism. The aim of this work was to investigate 32 polymorphisms in 24 genes of carcinogenic pathway to verify the influence of these genetic variants on the response to treatment with imatinib. Our results demonstrated that individuals with the recessive GG genotype for the rs2372536 variant in the ATIC gene are approximately three times more likely to experience treatment failure with imatinib (p = 0.045, HR = 2.726, 95% CI = 0.9986-7.441), as well as individuals with the TT genotype for the rs10821936 variant in the ARID5B gene, who also have a higher risk for treatment failure with imatinib over time (p = 0.02, HR = 0.4053, IC 95% = 0.1802-0.911). In conclusion, we show that variants in the ATIC and ARIDB5 gene, never screened in previous studies, could potentially influence the therapeutic response to imatinib in patients treated for CML.


Subject(s)
Benzamides , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , DNA-Binding Proteins/genetics , Drug Resistance, Neoplasm/genetics , Humans , Hydroxymethyl and Formyl Transferases , Imatinib Mesylate/therapeutic use , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Multienzyme Complexes , Nucleotide Deaminases , Piperazines , Pyrimidines/therapeutic use , Transcription Factors/genetics , Translocation, Genetic
15.
PLoS One ; 15(7): e0236033, 2020.
Article in English | MEDLINE | ID: mdl-32673332

ABSTRACT

In recent years, the incidence of tuberculosis (TB) has declined worldwide, although this disease still occurs at relatively high rates in Amerindian populations. This suggests that the genetic ancestry of Amerindians may be an important factor in the development of infections, and may account for at least some of the variation in infection rates in the different populations. The present study investigated the potential influence of Amerindian genetic ancestry on susceptibility to tuberculosis in an Amazon population. The study included 280 patients diagnosed with tuberculosis and 138 asymptomatic hospital employees with no history of TB, but who were in contact with bacterially active TB patients. Ancestry analysis was run on a set of 61 Ancestry-Informative Markers to estimate European, African, and Amerindian genetic ancestry using STRUCTURE v2.2. The TB group had significantly higher Amerindian ancestry in comparison with the control group, and significantly lower European ancestry. Amerindian ancestry in the 20-60% range was found to be the principal risk factor for increased susceptibility to TB. The results of the study indicate that Amerindian ancestry is an important risk factor for susceptibility to TB in the admixed population of the Brazilian Amazon region.


Subject(s)
Black People/statistics & numerical data , Genetic Variation , Genetics, Population , Indians, South American/statistics & numerical data , Mycobacterium tuberculosis/genetics , Tuberculosis/epidemiology , White People/statistics & numerical data , Brazil/epidemiology , Case-Control Studies , Female , Humans , Male , Middle Aged , Tuberculosis/genetics , Tuberculosis/microbiology
16.
PLoS One ; 15(4): e0231651, 2020.
Article in English | MEDLINE | ID: mdl-32294118

ABSTRACT

INTRODUCTION: The nudix hydrolase 15 (NUDT15) gene acts in the metabolism of thiopurine, by catabolizing its active metabolite thioguanosine triphosphate into its inactivated form, thioguanosine monophosphate. The frequency of alternative NUDT15 alleles, in particular those that cause a drastic loss of gene function, varies widely among geographically distinct populations. In the general population of northern Brazilian, high toxicity rates (65%) have been recorded in patients treated with the standard protocol for acute lymphoblastic leukemia, which involves thiopurine-based drugs. The present study characterized the molecular profile of the coding region of the NUDT15 gene in two groups, non-admixed Amerindians and admixed individuals from the Amazon region of northern Brazil. METHODS: The entire NUDT15 gene was sequenced in 64 Amerindians from 12 Amazonian groups and 82 admixed individuals from northern Brazil. The DNA was extracted using phenol-chloroform. The exome libraries were prepared using the Nextera Rapid Capture Exome (Illumina) and SureSelect Human All Exon V6 (Agilent) kits. The allelic variants were annotated in the ViVa® (Viewer of Variants) software. RESULTS: Four NUDT15 variants were identified: rs374594155, rs1272632214, rs147390019, andrs116855232. The variants rs1272632214 and rs116855232 were in complete linkage disequilibrium, and were assigned to the NUDT15*2 genotype. These variants had high frequencies in both our study populations in comparison with other populations catalogued in the 1000 Genomes database. We also identified the NUDT15*4 haplotype in our study populations, at frequencies similar to those reported in other populations from around the world. CONCLUSION: Our findings indicate that Amerindian and admixed populations from northern Brazil have high frequencies of the NUDT15 haplotypes that alter the metabolism profile of thiopurines.


Subject(s)
Indigenous Peoples/genetics , Pyrophosphatases/genetics , Antimetabolites, Antineoplastic/pharmacology , Antimetabolites, Antineoplastic/therapeutic use , Brazil , Humans , Mercaptopurine/pharmacology , Mercaptopurine/therapeutic use , Polymorphism, Single Nucleotide , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Pyrophosphatases/metabolism
17.
Leuk Res Rep ; 13: 100188, 2020.
Article in English | MEDLINE | ID: mdl-31867206

ABSTRACT

Acute Lymphoblastic Leukemia (ALL) is the most common childhood neoplasia. Studies have shown that susceptibility to ALL may be modulated by genetic variables. Our study investigated 21 genetic variants in the susceptibility of the population of the Brazilian Amazon region to B-cell ALL. The variants of the genes GGH, CEBPE, ARID5B, MTHFR and MTHFD1 were related to a protective effect against the development of ALL, whereas the variant of the gene ATIC was associated with a risk effect. The results suggest that genetic variants analyzed modulate of the risk of developing ALL in the studied population.

18.
Asian Pac J Cancer Prev ; 20(8): 2253-2258, 2019 08 01.
Article in English | MEDLINE | ID: mdl-31450892

ABSTRACT

Background: Despite decreasing global incidence trends, gastric cancer is still among the five most incident cancers in the world and the third cancer-related cause of death. In Brazil, differences in incidence and mortality exist depending on the geographic region studied. Objective: To describe the incidence, mortality, trends and age-period-cohort of gastric cancer in three cities of Brazil (Sao Paulo, Belem and Fortaleza), in the period 1990-2012. Mortality for gastric cancer in Brazil overall and by region was described. Methods: 33,462 incident cases of gastric cancer were identified from the population-based cancer registries and 23,424 deaths from mortality information system in residents of the three cities and in Brazil were included in the study. Data for incident cases were extracted from the Population Based Cancer Registries from the National Cancer Institute (INCA). Mortality data on gastric cancer were extracted from Information Technology Department of Brazilian Public Health Care System/Health Ministry (DATASUS/MS). Mortality and incidence age standardized rates were calculated. For trends analysis the Joinpoint Regression and age-period-cohort model were applied. Results: Belem presented the highest incidence rates for gastric adenocarcinoma. Decreasing incidence trends were identified in Sao Paulo (-7.8% in men; -6.3% in women) and in Fortaleza (-1.2% in men). Increasing incidence trends were observed for women in Belem (1.8%) and Fortaleza (1.1%). In Belem (Amazon area), there was an increased risk for gastric cancer in women born after the 1960s. Overall in Brazil mortality for gastric cancer is decreasing. Mortality trends showed significant reduction, for both sexes, in the three Brazilian cities. Conclusion: Incidence of gastric cancer is increasing in women born in the sixties in Belem (Amazon region) and Fortaleza (Northeast region). In Brazil there was increase in mortality in Northeast region and decrease in others regions. More update data on incidence for Amazon and Northeast region is needed.


Subject(s)
Adenocarcinoma/epidemiology , Adenocarcinoma/mortality , Mortality/trends , Stomach Neoplasms/epidemiology , Stomach Neoplasms/mortality , Adenocarcinoma/pathology , Adult , Age Factors , Aged , Aged, 80 and over , Brazil/epidemiology , Demography , Female , Follow-Up Studies , Health Status Disparities , Humans , Incidence , Male , Middle Aged , Prognosis , Sex Factors , Stomach Neoplasms/pathology , Survival Rate , Time Factors , Young Adult
19.
ABCD (São Paulo, Impr.) ; 26(4): 268-273, nov.-dez. 2013. tab
Article in Portuguese | LILACS | ID: lil-701247

ABSTRACT

A neoplasia gástrica é doença heterogênea e multifatorial, com incidência e mortalidade variando geograficamente. Aproximadamente 60% dos diagnósticos em pacientes de países ocidentais ocorrem nos estádios III ou IV. Nestes doentes, o melhor tratamento consiste na realização de procedimento cirúrgico. OBJETIVO: Identificar os aspectos epidemiológicos de pacientes diagnosticados com adenocarcinoma gástrico T4b. MÉTODOS: Estudo observacional, transversal, retrospectivo, de fonte secundária, dos pacientes diagnosticados com adenocarcinoma gástrico T4b através de estadiamento patológico. Foram analisados 815 prontuários, sendo 27 pacientes estudados. As variáveis investigadas foram: aspectos demográficos, principais queixas, fatores de risco, acesso ao serviço de saúde, aspectos cirúrgicos, morbidade, mortalidade e sobrevida. RESULTADOS: Vinte e dois eram homens (81,5%) e cinco mulheres (18,5%) com idade variando de 38 a 87 e média de 58,78 anos. O tempo de acesso ao serviço, em meses, variou de 1 a 120, com média de 12,5. Os sinais e sintomas mais prevalentes foram: perda de peso 23 (85,2%), epigastralgia 22 (81,5%), vômitos 16 (59,3%) e plenitude gástrica 12 (44,4%). A frequência de acometimento das estruturas adjacentes foi: pâncreas oito (29,6%), fígado sete (25,9%), cólon transverso seis (22,2%), intestino delgado seis (22,2%), mesocólon três (11,1%), baço um (3,7%) e vesícula biliar um (3,7%). Morbidades pós-operatórias ocorreram em 51,85% dos pacientes. Houve associação significativa entre mortalidade cirúrgica e ocorrência de fístula/deiscência, choque séptico e sangramento. A sobrevida ao final de seis meses foi de 63,27%. CONCLUSÃO: A média do tempo entre início dos sintomas e acesso ao serviço de saúde especializado foi elevada. Mais da metade dos pacientes apresentaram morbidades pós-operatórias. Os pacientes que apresentaram fístula/deiscência, sangramentos e choque séptico tiveram associação significativa com mortalidade cirúrgica. A sobrevida ao final de seis meses foi de 63,27%.


BACKGROUND: Gastric neoplasia is a heterogeneous and multifactorial disease and its incidence and mortality vary widely based on geographic location. Approximately 60% of the diagnoses of patients from occidental countries were made on the stages III and IV. The best treatment still is to realize a surgical procedure. AIM: Identify the epidemiological aspects of the patients diagnosed with T4b gastric adenocarcinoma. METHODS: The study was observational, transversal and retrospective; it was also based on secondary sources from patients diagnosed with T4b gastric adenocarcinoma, through pathologic stages. A total of 815 charts were analyzed and 27 patients studied. The variables were: demographic aspects, main symptoms, risk factors, access to health system, surgical aspects, morbidity, mortality and survival. RESULTS: Were included 22 men (81,5%) and five woman (18,5%), in the age group between 38 and 87 years old - median age of 58. The time, in months, to access the health system varied from one to 120, average of 12,5 months. The most prevalent signs and symptoms were: weight loss 23 (85,2%), epigastric pain 22 (81,5%), vomit 16 (59,3%) and gastric fullness 12 (44,4%). The frequency of the affected adjacent body structures was: pancreas 8 (29,6%), liver 7 (25,9%), transverse colon 6 (22,2%), small intestine 6 (22,2%), mesocolon 3 (11,1%), spleen 1 (3,7%) and gallbladder 1 (3,7%). Postoperative morbidity occurred in 51, 85% of the patients. There were a significative association between surgical mortality and the occurrence of fistula/ dehiscence, septic shock and bleeding. The survival rate after six months was 63,27%. CONCLUSION: The mean time between onset of symptoms and access to specialized health services was high. More than half of the patients had postoperative morbidities. Patients who had fistula / dehiscence, bleeding and septic shock were significantly associated with surgical mortality. The survival rate after six months was 63.27%.


Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Adenocarcinoma/epidemiology , Stomach Neoplasms/epidemiology , Adenocarcinoma/pathology , Adenocarcinoma/surgery , Cross-Sectional Studies , Hospitals, University , Neoplasm Staging , Retrospective Studies , Stomach Neoplasms/pathology , Stomach Neoplasms/surgery , Time Factors
20.
Rev Col Bras Cir ; 38(2): 100-4, 2011.
Article in English, Portuguese | MEDLINE | ID: mdl-21710047

ABSTRACT

OBJECTIVE: To evaluate the epidemiological aspects of surgical patients with gallbladder cancer (GC) enrolled in a University Hospital in Bethlehem (State of Pará - PA), in the period 1999-2009. METHODS: observational, retrospective, descriptive and analytical study of secondary sources of patients with GC in the period 1999-2009. We analyzed 75 medical records, with 34 patients studied. The information collected was used for the TNM tumor staging of GC and to characterize the clinical and surgical population. RESULTS: 79% were female, mean age 66.2 ± 11 years and duration of symptoms was 10.8 ± 17.2 months, with no statistical relationship with the stage of disease. Pain in right upper quadrant, nausea and jaundice prevailed as signs / symptoms. Gallstones were present in 91% of cases and were positive in 100% of patients with stage I / II. The sensitivity of ultrasound to preoperatively suggest GC was 14.28%. The simplest operation performed was cholecystectomy, with the predominant intraoperative finding being hepatic invasion. Adenocarcinoma was the predominant histologic type, especially for stages III and IV. CONCLUSION: The present study showed high incidence of gallstone disease. Advanced stage adenocarcinoma was the most prevalent. This resulted in a low rate of operations with curative intent, in 30% of the patients, and a mortality rate of 21%. The appreciation of symptoms and early investigation by imaging could facilitate treatment in early stages of GC, providing a better prognosis for patients.


Subject(s)
Gallbladder Neoplasms , Aged , Brazil , Female , Gallbladder Neoplasms/diagnosis , Gallbladder Neoplasms/surgery , Hospitals , Humans , Male , Middle Aged , Referral and Consultation , Retrospective Studies , Time Factors
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