RESUMO
INTRODUCTION: Long-term exposure to high-risk human papillomavirus (Hr-HPV) is a well-known necessary condition for development of cervical cancer. The aim of this study is to screen for Hr-HPV using vaginal self-sampling, which is a more effective approach to improve women's adherence and increase screening rates. METHODS: This pilot study included a total of 100 Women living with HIV (WLWHIV), recruited from the Center for Listening, Care, Animation, and Counseling of People Living with HIV in Bamako. Hr-HPV genotyping was performed on Self-collected samples using the Cepheid GeneXpert instrument. RESULTS: The median age of WLWHIV was 44 (interquartile range [IQR], 37-50) years. Approximately 92% of the study participants preferred self-sampling at the clinic, and 90% opted to receive result notifications via mobile phone contact. The overall prevalence of Hr-HPV among study participants was 42.6%, and the most frequent Hr-HPV sub-types observed were HPV18/45 (19.1%), HPV31/35/33/52/58 (13.8%), and HPV39/68/56/66 (12.8%), followed by HPV16 (5.3%), and HPV51/59 (5.3%). WLWHIV under 35 years of age had a higher frequency of Hr-HPV compared to their older counterparts, with rates of 30% versus 11.1% (p = 0.03). The duration of antiretroviral treatment showed an inverse association with Hr-HPV negativity, with patients on treatment for 15 (IQR, 10-18) years versus 12 (IQR = 7-14) years for Hr-HPV positive patients (95% CI [1.2-5.8], t = 3.04, p = 0.003). WLWHIV with baseline CD4 T-Cell counts below 200 exhibited a higher frequency of Hr-HPV compared to those with baseline CD4 T-Cell counts above 200 (17.9% versus 1.9%, p = 0.009). However, other demographics and clinical factors, such as marital status, age of sexual debut, parity, education, history of abortion, history of preeclampsia, and cesarean delivery, did not influence the distribution of Hr-HPV genotypes. CONCLUSION: Our findings indicate that WLWHIV under the age of 35 years old exhibited the highest prevalence of Hr-HPV infection, with HPV18/45 being the most prevalent subtype. Additionally, WLWHIV with baseline CD4 T-Cell counts below 200 showed the highest infection rates.
Assuntos
Genótipo , Infecções por HIV , Papillomaviridae , Infecções por Papillomavirus , Humanos , Feminino , Adulto , Projetos Piloto , Infecções por Papillomavirus/virologia , Infecções por Papillomavirus/epidemiologia , Infecções por HIV/virologia , Infecções por HIV/epidemiologia , Pessoa de Meia-Idade , Prevalência , Papillomaviridae/genética , Papillomaviridae/classificação , Papillomaviridae/isolamento & purificação , Mali/epidemiologia , Pacientes Ambulatoriais/estatística & dados numéricos , Papillomavirus HumanoRESUMO
BACKGROUND: High risk human papillomaviruses (HR-HPV) have a causal role in cervical oncogenesis, and HIV-mediated immune suppression allows HR-HPV to persist. We studied whether vaginal microbiome community state types (CSTs) are associated with high-grade precancer and/or invasive cervical cancer (HSIL/ICC). METHODS: This was a cross-sectional study of adult women with cervical cancer screening (CCS) at the Jos University Teaching Hospital (JUTH) in Jos, Nigeria, between January 2020 and February 2022. Cervical swabs underwent HPV genotyping (Anyplex™ II HPV28). Cervico-vaginal lavage (CVL) sample was collected for 16 S rRNA gene amplicon sequencing. We used multivariable logistic regression modelling to assess associations between CSTs and other factors associated with HSIL/ICC. RESULTS: We enrolled 155 eligible participants, 151 with microbiome data for this analysis. Women were median age 52 (IQR:43-58), 47.7% HIV positive, and 58.1% with HSIL/ICC. Of the 138 with HPV data, 40.6% were negative for HPV, 10.1% had low-risk HPV, 26.8% had single HR-HPV, and 22.5% had multiple HR-HPV types. The overall prevalence of any HR-HPV type (single and multiple) was 49.3%, with a higher proportion in women with HSIL/ICC (NILM 31.6%, LSIL 46.5%, HSIL 40.8%, and 81.5% ICC; p = 0.007). Women with HIV were more likely to have HSIL/ICC (70.3% vs. 29.7% among women without HIV). In crude and multivariable analysis CST was not associated with cervical pathology (CST-III aOR = 1.13, CST-IV aOR = 1.31). However, in the presence of HR-HPV CST-III (aOR = 6.7) and CST-IV (aOR = 3.6) showed positive association with HSIL/ICC. CONCLUSION: Vaginal microbiome CSTs were not significantly associated with HSIL/ICC. Our findings suggest however, that CST could be helpful in identifying women with HSIL/ICC and particularly those with HR-HPV. Characterization of CSTs using point-of-care molecular testing in women with HR-HPV should be studied as an approach to improve early detection and cervical cancer prevention. Future longitudinal research will improve our understanding of the temporal effect of non-optimal CST, HR-HPV, and other factors in cervical cancer development, prevention, and control.
Assuntos
Gardnerella , Papillomavirus Humano , Lactobacillus , Microbiota , Lesões Pré-Cancerosas , Neoplasias do Colo do Útero , Humanos , Feminino , Adulto , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia , Lesões Pré-Cancerosas/epidemiologia , Lesões Pré-Cancerosas/patologia , Lesões Pré-Cancerosas/virologia , Nigéria/epidemiologia , Risco , Pessoa de Meia-Idade , Estudos Transversais , Papillomavirus Humano/classificação , Papillomavirus Humano/genética , Papillomavirus Humano/isolamento & purificação , Lactobacillus/classificação , Lactobacillus/genética , Lactobacillus/isolamento & purificação , Gardnerella/classificação , Gardnerella/genética , Gardnerella/isolamento & purificação , Gradação de TumoresRESUMO
Methylenetetrahydrofolate reductase (MTHFR) plays a major role in the metabolism of folates and homocysteine, which in turn can affect gene expression and ultimately promote the development of breast cancer. Thus, mutations in the MTHFR gene could influence homocysteine, methionine, and S-adenosylmethionine levels and, indirectly, nucleotide levels. Imbalance in methionine and S-adenosylmethionine synthesis affects protein synthesis and methylation. These changes, which affect gene expression, may ultimately promote the development of breast cancer. We therefore hypothesized that such mutations could also play an important role in the occurrence and pathogenesis of breast cancer in a Malian population. In this study, we used the PCR-RFLP technique to identify the different genotypic profiles of the C677T MTHFR polymorphism in 127 breast cancer women and 160 healthy controls. The genotypic distribution of the C677T polymorphism in breast cancer cases was 88.2% for CC, 11.0% for CT, and 0.8% for TT. Healthy controls showed a similar distribution with 90.6% for CC, 8.8% for CT, and 0.6% for TT. We found no statistical association between the C677T polymorphism and breast cancer risk for the codominant models CT and TT (p > 0.05). The same trend was observed when the analysis was extended to other genetic models, including dominant (p = 0.50), recessive (p = 0.87), and additive (p = 0.50) models. The C677T polymorphism of MTHFR gene did not influence the risk of breast cancer in the Malian samples.
Assuntos
Neoplasias da Mama , Metilenotetra-Hidrofolato Redutase (NADPH2) , Feminino , Humanos , Neoplasias da Mama/genética , Homocisteína , Mali , Metionina , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , S-AdenosilmetioninaRESUMO
OBJECTIVES: The main objective of this study was to evaluate the effect of CYP2B6 and CYP3A4 polymorphisms on the virological and immunologic responses of HIV patients. A total of 153 HIV-positive patients were enlisted for the study. PATIENTS AND METHODS: Viral load and median CD4 T cell counts were evaluated at baseline and month 6 (M6). Samples were identified using TaqMan genotyping assays. RESULTS: The AG in CYP2B6 rs2279343 was associated with VLS compared to homozygous AA. In the dominant model, the AG/GG genotypes were associated with VLS compared to the AA genotype. Moreover, in overdominant model, the AG genotype was associated with VLS compared to AA/GG. Regarding immunological response, only the AG in SNP rs2279343 CYP2B6 was associated with an increase in CD4 cell count between baseline and M6. In CYP2B6 rs3745274, the CD4 cell count at M6 was higher than that of baseline for GG carriers and for GT carriers. In CYP3A4 rs2740574, the TC carriers showed a higher median CD4 count at M6 compared to that of the baseline count, as well as for CC carriers. The best genotypes combination associated with CD4 cell count improvement were AA/AG in SNP rs2279343 and GG/GT in SNP rs3745274. CONCLUSION: Our findings support the fact that CYP2B6 rs2279343 could help in the prediction of VLS and both SNPs rs3745274 and rs2279343 in CYP2B6 and CYP3A4 rs2740574 were associated with immune recovery in Malian HIV-positive patients.
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Fármacos Anti-HIV , Benzoxazinas , Ciclopropanos , Infecções por HIV , Alcinos , Fármacos Anti-HIV/farmacologia , Benzoxazinas/farmacologia , Ciclopropanos/farmacologia , Citocromo P-450 CYP2B6/genética , Inibidores do Citocromo P-450 CYP2B6/farmacologia , Citocromo P-450 CYP3A/genética , Genótipo , Infecções por HIV/tratamento farmacológico , Infecções por HIV/enzimologia , Infecções por HIV/genética , Humanos , Polimorfismo de Nucleotídeo ÚnicoRESUMO
A literature review showed some discrepancies regarding the association of -592C/A with the risk of cervical cancer. To allow more precise analysis of the data by increasing the number of cases studied and more acceptable generalization by considering results from different sources, the present meta-analysis was performed on available published studies that explored the relationship between SNP-592C/A of the IL-10 gene and the risk of cervical cancer. Eleven available studies, including 4187 cases and 3311 controls, were included in this study investigating the relationship between the -592C/A polymorphism of IL-10 and cervical cancer risk. Fixed-effects or random-effects models were performed with pooled odds ratios (ORs). Heterogeneity and bias tests were performed by the inconsistency test and funnel plot, respectively. The overall analysis showed an increased susceptibility to cervical cancer with the -592C/A polymorphism of the IL-10 gene for the recessive model (OR = 1.30, 95% CI = 1.14-1.49), dominant model (OR = 1.36, 95% CI = 1.09-1.70), and additive model (OR = 1.25, 95% CI = 1.09-1.44). Regarding ethnicity, a significant association of the -592C/A polymorphism of the IL-10 gene was linked to an elevated risk of cervical cancer for all genetic models (recessive, dominant, and additive) in the Asian populations and for the recessive and additive models in Caucasians with P < 0.05. The -592C/A polymorphism of the IL-10 gene may be considered a risk factor for cervical cancer.
Assuntos
Interleucina-10 , Neoplasias do Colo do Útero , Povo Asiático , Feminino , Predisposição Genética para Doença , Humanos , Interleucina-10/genética , Polimorfismo de Nucleotídeo Único/genética , Fatores de Risco , Neoplasias do Colo do Útero/genéticaRESUMO
BACKGROUND: Schizophrenia is a relatively common disease worldwide with a point prevalence of around 5/1000 in the population. The aim of this present work was to assess the demographic, clinical, familial, and environmental factors associated with schizophrenia in Mali. METHODS: This was a prospective descriptive study on a series of 164 patients aged at least 12 years who came for a follow-up consultation at the psychiatry department of the University Hospital Center (CHU) Point G in Mali between February 2019 and January 2020 for schizophrenia spectrum disorder as defined by DSM-5 diagnostic criteria. RESULTS: Our results revealed that the male sex was predominant (80.5%). The 25-34 age group was more represented with 44.5%. The place of birth for the majority of our patients was the urban area (52.4%), which also represented the place of the first year of life for the majority of our patients (56.1%). We noted that the unemployed and single people accounted for 56.1 and 61% respectively. More than half of our patients 58.5% reported having reached secondary school level. With the exception of education level, there was a statistically significant difference in the distribution of demographic parameters. Familial schizophrenia cases accounted for 51.7% versus 49.3% for non-familial cases. The different clinical forms were represented by the paranoid form, followed by the undifferentiated form, and the hebephrenic form with respectively 34, 28 and 17.1%. We noted that almost half (48.8%) of patients were born during the cold season. Cannabis use history was not observed in 68.7% of the patients. The proportions of patients with an out-of-school father or an out-of-school mother were 51.2 and 64.2%, respectively. CONCLUSION: The onset of schizophrenia in the Malian population has been associated with socio-demographic, clinical, genetic and environmental characteristics.
Assuntos
Esquizofrenia , Manual Diagnóstico e Estatístico de Transtornos Mentais , Escolaridade , Humanos , Masculino , Estudos Prospectivos , Esquizofrenia/epidemiologia , Estações do AnoRESUMO
BACKGROUND: Breast cancer, the most common tumor in women in Mali and worldwide has been linked to several risk factors, including genetic factors, such as the PIN3 16-bp duplication polymorphism of TP53. The aim of our study was to evaluate the role of the PIN3 16-bp duplication polymorphism in the susceptibility to breast cancer in the Malian population and to perform a meta-analysis to better understand the correlation with data from other populations. METHODS: We analyzed the PIN3 16-bp duplication polymorphism in blood samples of 60 Malian women with breast cancer and 60 healthy Malian women using PCR. In addition, we performed a meta-analysis of case-control study data from international databases, including Pubmed, Harvard University Library, Genetics Medical Literature Database, Genesis Library and Web of Science. Overall, odds ratio (OR) with 95% CI from fixed and random effects models were determined. Inconsistency was used to assess heterogeneity between studies and publication bias was estimated using the funnel plot. RESULTS: In the studied Malian patients, a significant association of PIN3 16-bp duplication polymorphism with breast cancer risk was observed in dominant (A1A2 + A2A2 vs. A1A1: OR = 2.26, CI 95% = 1.08-4.73; P = 0.02) and additive (A2 vs. A1: OR = 1.87, CI 95% = 1.05-3.33; P = 0.03) models, but not in the recessive model (P = 0.38). In the meta-analysis, nineteen (19) articles were included with a total of 6018 disease cases and 4456 controls. Except for the dominant model (P = 0.15), an increased risk of breast cancer was detected with the recessive (OR = 1.46, 95% CI = 1.15-1.85; P = 0.002) and additive (OR = 1.11, 95% CI = 1.02-1.19; P = 0.01) models. CONCLUSION: The case-control study showed that PIN3 16-bp duplication polymorphism of TP53 is a significant risk factor for breast cancer in Malian women. These findings are supported by data from the meta-analysis carried out on different ethnic groups around the world.
Assuntos
Pareamento de Bases/genética , Neoplasias da Mama/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Polimorfismo Genético , Proteína Supressora de Tumor p53/genética , Adulto , Estudos de Casos e Controles , Feminino , Heterogeneidade Genética , Humanos , Mali , Modelos Genéticos , Razão de Chances , Viés de Publicação , Fatores de RiscoRESUMO
BACKGROUND: The effect of the p.Arg72Pro variant of the P53 gene on the risk of development ofbreast cancer remains variable in populations. However, the use ofstrategies such aspoolingage-matched controls with disease may provide a consistent meta-analysis. Our goal was to perform a meta-analysis in order to assess the association of p.Arg72Pro variant of P53 gene with the risk of breast cancer. METHODS: Databases such as PubMed, Genetics Medical Literature, Harvard University Library, Web of Science and Genesis Library were used to search articles. Case-control studies with age-matched on breast cancer havingevaluated the genotype frequencies of the TP53 p.Arg72Pro polymorphism were selected. The fixed and random effects (Mantel-Haenszel) were calculated using pooled odds ratio of 95% CI to determine the risk of disease. Inconsistency was calculated to determine heterogeneity among the studies. The publication bias was estimated using the funnel plot. RESULTS: Twenty-one publications with 7841 cases and 8876 controls were evaluated in this meta-analysis. Overall, our results suggested that TP53 p.Arg72Pro was associated with the risk of breast cancer for the dominant model (OR = 1.09, 95% CI = 1.02-1.16, P = 0.01) and the additive model (OR = 1.09, 95% CI = 1.01-1.17, P = 0.03), but not for the recessive model (OR = 1.07, 95% CI = 0.97-1.18, P = 0.19). According to the ethnic group analysis, Pro allele was associated with the risk of breast cancer in Caucasians for the dominant model and additive model (P = 0.02), and Africans for the recessive model and additive model (P = 0.03). CONCLUSIONS: This meta-analysis found a significant association between TP53 p.Arg72Pro polymorphism and the risk of breast cancer. Individuals carrying at least one Pro allele were more likely to have breast cancer than individuals harboring the Arg allele.
Assuntos
Substituição de Aminoácidos , Neoplasias da Mama/genética , Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único , Proteína Supressora de Tumor p53/genética , Alelos , Neoplasias da Mama/diagnóstico , Estudos de Casos e Controles , Feminino , Frequência do Gene , Genótipo , Humanos , Fatores de RiscoRESUMO
Glutathione S-transferase genes, known to be highly polymorphic, are implicated in the process of phase II metabolism of many substrates, including xenobiotics, anticancer and anti-infective drugs. The detoxification activity is linked to individual genetic makeup. Therefore, the identification of alleles and genotypes in these genes within a population may help to better design genetic susceptibility and pharmacogenetic studies. We performed the present study to establish the frequencies of the GSTM1, GSTT1, and GSTP1 c. 313A > G (rs1695) polymorphisms in 206 individuals of the Malian healthy population. GSTM1 and GSTT1 were genotyped by using multiplex polymerase chain reaction, whereas genotypes of GSTP1 were identified by polymerase chain reaction followed by restriction fragment length polymorphism. The frequencies of GSTM1-null and GSTT1-null genotypes were respectively 24.3 and 41.3%. The observed genotype frequencies for GSTP1 were 25.73% homozygous wild-type AA, 49.03% heterozygous AG and 25.24% homozygous mutant GG. The frequency of GSTP1-A allele was 50.24% versus 49.76% for the GSTP1-G allele. The distribution of these three genes was homogeneous between men and women (p > 0.05). We found no statistical association between the presence of a particular profile of GSTM1 or GSTT1 with the genotypes of GSTP1 (p > 0.05). Nevertheless, we noticed that the majority of the individuals harboring the GSTM1-present or the GSTT1-present harbor also the GSTP1-AG genotype. In addition, the triple genotype GSTM1-present/GSTT1-present/AG was the most frequent with 25.2%. Our findings will facilitate future studies regarding genetic associations of multifactorial diseases and pharmacogenetic, thus opening the way to personalized medicine in our population.
Assuntos
Glutationa S-Transferase pi/genética , Glutationa Transferase/genética , Desintoxicação Metabólica Fase II/genética , Adolescente , Adulto , Idoso , Alelos , Feminino , Frequência do Gene/genética , Predisposição Genética para Doença/genética , Genótipo , Glutationa S-Transferase pi/metabolismo , Glutationa Transferase/metabolismo , Voluntários Saudáveis , Humanos , Masculino , Mali , Desintoxicação Metabólica Fase II/fisiologia , Pessoa de Meia-Idade , Polimorfismo Genético/genética , Fatores de RiscoRESUMO
BACKGROUND: Breast cancer is the most common cause of cancer death among women. Several studies have investigated the relationship between the C3435T polymorphism of ABCB1 gene and risk of breast cancer; but the results are conflicting. In the present study, we sought to assess the relationship between the C3435T polymorphism in ABCB1 gene and the risk of breast cancer in a sample of the Moroccan population. METHODS: A case control study was performed on 60 breast cancer patients and 68 healthy women. The ABCB1 C3435T polymorphism was analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Furthermore, a meta-analysis including 16 studies with 6094 cases of breast cancer and 8646 controls was performed. RESULTS: Genotype frequencies were 50 % for CC, 33.3 % for CT and 16.7 % for TT in patients and 41.2 % for CC, 48.5 % for CT and 10.3 % for TT respectively in the control group. This difference was not statistically significant. The same trend as observed in the allele distribution between patients and controls (P = 0.84). Findings from the meta-analysis showed that the ABCB1 C3435T polymorphism was not associated with an increased risk of breast cancer in the dominant model (OR = 0.907; 95 % CI = 0.767-1.073; P = 0.25) as well as in the recessive model (OR = 1.181; 95 % CI = 0.973-1.434; P = 0.093) and in the allele contrast model (OR = 1.098; 95 % CI = 0.972-1.240; P = 0.133). However, the stratification of studies on ethnic basis showed that the TT genotype was associated with the risk of breast cancer in Asians (OR = 1.405; 95 % CI = 1.145-1.725; P = 0.001), Caucasians (OR = 1.093; 95 % CI = 1.001-1.194; P = 0.048) and North African (OR = 2.028; 95 % CI = 1.220-3.371; P = 0.006). CONCLUSIONS: We have noted that the implication of C3435T variant on the risk of breast cancer was ethnicity-dependent. However, there is no evidence that ABCB1 C3435T polymorphism could play a role in susceptibility to breast cancer in Morocco. Further studies with a larger sample size, extended to other polymorphisms are needed to understand the influence of ABCB1 genetic variants on the risk of breast cancer.
Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Alelos , Neoplasias da Mama/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Substituição de Aminoácidos , Biomarcadores Tumorais , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/patologia , Estudos de Casos e Controles , Feminino , Frequência do Gene , Estudos de Associação Genética , Genótipo , Humanos , Marrocos/epidemiologia , Estadiamento de Neoplasias , RiscoRESUMO
BACKGROUND: Identification of specific mutations in cancer patients may lead to the discovery of genes, which can affect susceptibility and/or prognosis. It has previously been reported that mutations in BRCA1 and BRCA2 genes are linked to breast cancer. Here, we evaluated the use of the High Resolution Melting (HRM) approach to screen for mutations in exon 11 of BRCA1 gene in Moroccan patients. METHODS: HRM analysis was used to screen exon 11 from 71 breast cancer patients in order to detect different variants. Conventional Sanger sequencing was used to confirm the presence of possible mutations. Distribution of different SNPs was determined by SNaPshot analysis software. RESULTS: In order to assess the efficacy of the HRM approach to screen for mutations, especially in diagnosis, we first used two samples with previously known mutations, "2924delA and 3398delC". Indeed, these previously known sequence variants were detected by the HRM approach and yielded melting curves with atypical shape relative to wild-type control sequences. We then analyzed, 69 samples from breast cancer patients using the HRM method, and were able to detect two samples with atypical curves. Sequencing of the two samples, using the conventional Sanger approach, confirmed the presence of the same SNP (c.2612C > T) in both samples. CONCLUSIONS: Our results strongly suggest that the HRM approach represents a reliable and highly sensitive method for mutation scanning, especially in diagnosis.
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Proteína BRCA1/genética , Neoplasias da Mama/diagnóstico , Análise Mutacional de DNA/métodos , Detecção Precoce de Câncer/métodos , Neoplasias da Mama/genética , Éxons , Feminino , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Marrocos , Mutação , Polimorfismo de Nucleotídeo Único , Sensibilidade e EspecificidadeRESUMO
TP53 is a tumor suppressor gene involved in cell cycle progression control, DNA damage repair, genomic stability, and apoptosis. Some polymorphisms in this gene have been associated with the development of a number of cancers including breast carcinoma. PIN3 Ins16bp polymorphism has been widely studied in different populations for an association with breast cancer risk. In most case-control studies, a duplicated allele has been more frequent in cases rather than controls but there are also inconsistent results. The present study aimed to assess the association of PIN3 Ins16bp polymorphism of p53 with breast cancer risk in Moroccan population. This case-control study was performed on 105 female patients with confirmed breast cancer and 114 healthy controls. The genotype frequency was 69.5 % (A1A1), 26.7 % (A1A2), and 3.8 % (A2A2) in patients and 68.4 % (A1A1), 24.6 % (A1A2), and 7 % (A2A2) in controls. No statistically significant association was observed between PIN3 Ins16bp polymorphism and breast cancer risk with odds ratio of 1.07 (confidence interval (CI) = 0.58-1.97, p = 0.83) for the heterozygous A1A2 and 0.53 (CI = 0.15-1.85, p = 0.32) for mutated homozygous A2A2.According to our preliminary genetic analysis, PIN3 Ins16pb polymorphism could not be assessed as a marker of risk factor for predisposition to breast cancer in Moroccan population. However, a high frequency of A2 allele (19.3 %) in our population suggested that PIN3 Ins16pb polymorphism may be a valuable marker for study in other cancers with larger groups.
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Neoplasias da Mama/genética , Íntrons , Polimorfismo Genético , Proteína Supressora de Tumor p53/genética , Adulto , Alelos , Neoplasias da Mama/patologia , Estudos de Casos e Controles , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Humanos , Pessoa de Meia-Idade , Marrocos , Metástase Neoplásica , Razão de Chances , Fatores de Risco , Carga Tumoral , Adulto JovemRESUMO
BACKGROUND: The pathogenesis of inflammatory bowel disease (IBD) involves interactions between the host genetic susceptibility, intestinal microflora and mucosal immune responses through the pattern recognition receptor. Polymorphisms in toll-like receptor 4 (TLR4) induce an aberrant immune response to indigenous intestinal flora, which might favor IBD development. In this study, we aimed to determine whether TLR4 gene was associated with Crohn's disease (CD) and ulcerative colitis (UC) among Moroccan patients, and evaluated its correlation with clinical manifestation of the disease. METHODS: The study population comprised 117 patients with IBD and 112 healthy unrelated blood donors. TLR4 polymorphisms: Asp299Gly and Thr399Ile were genotyped by polymerase chain reaction-restriction fragment length polymorphism. PCR products were cleaved with Nco I for the Asp299Gly polymorphism and Hinf I for the Thr399Ile polymorphism. Meta-analysis was performed to test the association of 299Gly and 399Ileu carriage with CD, UC and the overall IBD risk. RESULTS: Our study revealed that the frequency of Asp299Gly and Thr399Ile did not differ significantly between patients and controls in the Moroccan population. However, meta-analysis demonstrated significantly higher frequencies of both Asp299Gly and Thr399Ile SNPs in IBD and CD and for 399Ileu carriage in UC patients. CONCLUSION: The meta-analysis provides evidence that TLR4 polymorphisms confer a significant increased risk for the overall IBD development.
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Colite Ulcerativa/genética , Doença de Crohn/genética , Polimorfismo Genético , Receptor 4 Toll-Like/genética , Adulto , Humanos , Doenças Inflamatórias Intestinais/genética , Marrocos , Polimorfismo de Fragmento de RestriçãoRESUMO
Background: Whether treatment of human immunodeficiency virus (HIV) with antiretroviral therapy (ART) is associated with lower risk of mental health disorders (MHDs) among people with HIV (PWH) remains unknown. We aim to determine the association between HIV and MHDs and whether ART alters the risk of MHDs among PWH in the US adult population. Methods: We conducted a real-world study using the Merative MarketScan claims database (2016-2020), identifying individuals with HIV (diagnosed using International Classification of Diseases, Tenth Revision, Clinical Modification codes) and those without HIV. A multivariable stratified Cox proportional hazard regression model was conducted to examine the association of HIV treatment status with MHDs, adjusting for potential confounders. Additionally, we sought to determine the effect modification of ART on the relationship between living with HIV and MHDs. Results: A total of 313 539 individuals, with a mean age of 44.2 (standard deviation, 11.4) years, predominantly males (81.2%), residing in the South region of the US (50.9%) were included in the present analysis. During 671 880 person-years of follow-up, 46 235 incident MHD cases occurred. In the multivariable Cox proportional hazard model, living with HIV was associated with higher risk of incident MHDs. Relative to those without HIV, the adjusted hazard ratio was 1.85 (95% confidence interval [CI], 1.79-1.92; P < .001) for those with HIV on treatment, and 2.70 (95% CI, 2.59-2.82; P < .001) for those with HIV without any treatment. Stronger associations between HIV and MHDs were observed in men relative to women, among those aged 18-34 years relative to those aged 55-63 years, and among those with no overweight/obesity relative to obese individuals (Pinteraction < .001 for all). Conclusions: HIV was associated with an increased risk of developing MHDs. However, HIV treatment mitigated the risk.
RESUMO
While Hepatitis B virus (HBV) and the human immunodeficiency virus (HIV) are endemic in West Africa, the prevalence of HBV/HIV coinfection and their associated risk factors in children remains unclear. In this review, we sought to assess HBsAg seroprevalence among 0- to 16-year-olds with and without HIV in West African countries and the risk factors associated with HBV infection in this population. Research articles between 2000 and 2021 that reported the prevalence of HBV and associated risk factors in children in West Africa were retrieved from the literature using the Africa Journals Online (AJOL), PubMed, Google Scholar, and Web of Science databases as search tools. StatsDirect, a statistical software, was used to perform a meta-analysis of the retained studies. HBV prevalence and heterogeneity were then assessed with a 95% confidence interval (CI). Publication bias was evaluated using funnel plot asymmetry and Egger's test. Twenty-seven articles conducted across seven West African countries were included in this review. HBV prevalence among persons aged 0 to 16 years was 5%, based on the random analysis, given the great heterogeneity of the studies. By country, the highest prevalence was observed in Benin (10%), followed by Nigeria (7%), and Ivory Coast (5%), with Togo (1%) having the lowest. HBV prevalence in an HIV-infected population of children was (9%). Vaccinated children had lower HBV prevalence (2%) than unvaccinated children (6%). HBV prevalence with a defined risk factor such as HIV co-infection, maternal HBsAg positivity, undergoing surgery, scarification, or being unvaccinated ranged from 3-9%. The study highlights the need to reinforce vaccination of newborns, screening for HBV, and HBV prophylaxis among pregnant women in Africa, particularly in West Africa, to achieve the WHO goal of HBV elimination, particularly in children.
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Coinfecção , Infecções por HIV , Hepatite B , Humanos , Feminino , Criança , Recém-Nascido , Gravidez , Vírus da Hepatite B , Antígenos de Superfície da Hepatite B , HIV , Estudos Soroepidemiológicos , Hepatite B/epidemiologia , Infecções por HIV/epidemiologia , Côte d'Ivoire/epidemiologia , Prevalência , Coinfecção/epidemiologiaRESUMO
Excessive consumption of red and processed meat has been associated with a higher risk of developing colorectal cancer. There are many attempts to explain the risk of colorectal cancer associated with the consumption of red and processed meat: The temperature cooking of meat such as grilling and smoking contribute to the formation of mutagenic compounds including heterocyclic amines and polycyclic aromatic hydrocarbons.Heme iron in red meat is involved in the formation of N-nitroso compounds and lipid peroxidation products in the digestive tract.Fatty red meat is involved in the production of secondary bile acids by the bacteria of the gut microbiota. Many of the products formed are genotoxic and can cause DNA damage and initiate carcinogenesis of colorectal cancer. Various mechanisms contributing to their genotoxic role have been established in human and animal studies. In addition, there is increasing evidence that compounds formed from red and processed meat interact with the gut microbiota in colorectal cancer pathways. Although several early studies in animals and humans suggest a direct causal role of the gut microbiota in the development of colorectal cancer, the links between diet, gut microbiota, and colonic carcinogenesis are largely associations rather than proven causal relationships. Various biological mechanisms, including inflammation and oxidative stress can lead to DNA damage, gut dysbiosis, and therefore increase the risk of colorectal cancer. Dysbiosis of the gut microbiota may increase the risk of colorectal cancer through dietary component promotion of colonic carcinogenesis. In this paper, we review and update current knowledge about the relationships between red meat consumption, gut microbiota, and colorectal cancer.
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BACKGROUND: Cervical cancer is the fourth most common cancer among women worldwide, with an estimate of 570,000 new cases and about 311,000 deaths annually. Low-resource countries, including those in sub-Saharan Africa, have the highest-burden with an estimate of 84 % of all cervical cancers. This study examines the prevalence and socio-demographic-economic factors associated with cervical cancer screening in sub-Saharan Africa. METHODS: A weighted population-based cross-sectional study using Demographic and Health Surveys data. We used available data on cervical cancer screening between 2011 and 2018 from the Demographic and Health Surveys for five sub-Saharan African countries (Benin, Ivory Coast, Kenya, Namibia, and Zimbabwe). The study population included women of childbearing age, 21-49 years (n = 28,976). We fit a multivariable Poisson regression model to identify independent factors associated with cervical cancer screening. RESULTS: The overall weighted prevalence of cervical cancer screening was 19.0 % (95 % CI: 18.5 %-19.5 %) ranging from 0.7 % in Benin to 45.9 % in Namibia. Independent determinants of cervical cancer screening were: older age (40-49 years) adjusted prevalence ratio (aPR) = 1.77 (95 % CI: 1.64, 1.90) compared with younger age (21-29 years), secondary/higher education (aPR = 1.51, 95 CI: 1.28-1.79) compared with no education, health insurance (aPR = 1.53, 95 % CI: 1.44-1.61) compared with no insurance, and highest socioeconomic status (aPR = 1.39, 95 % CI: 1.26-1.52) compared with lowest. CONCLUSION: The prevalence of cervical cancer screening is substantially low in sub-Saharan Africa countries and shows a high degree of between-country variation. Interventions aimed at increasing the uptake of cervical cancer screening in sub-Saharan Africa are critically needed.
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Detecção Precoce de Câncer/estatística & dados numéricos , Neoplasias do Colo do Útero/diagnóstico , Adulto , África Subsaariana/epidemiologia , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-Idade , Prevalência , Fatores Socioeconômicos , Neoplasias do Colo do Útero/epidemiologia , Adulto JovemRESUMO
ABSTRACT: Cytochrome P450 enzymes play a central role in the phase I biotransformation process of a wide range of compounds, including xenobiotics, drugs, hormones and vitamins. It is noteworthy that these enzymes are highly polymorphic and, depending on the genetic makeup, an individual may have impaired enzymatic activity. Therefore, the identification of genetic variants in these genes could facilitate the implementation of pharmacogenetic studies and genetic predisposition to multifactorial diseases. We have established the frequencies of CYP2B6 (rs3745274; rs2279343) and CYP3A4 (rs2740574) alleles and genotypes in 209 healthy Malian subjects using TaqMan drug metabolism genotyping assays for allelic discrimination. Allele frequencies were 37% for CYP2B6 rs3745274; 38% for CYP2B6 rs2279343; and 75% for CYP3A4 rs2740574 respectively. Overall, the frequencies observed in Mali are statistically comparable to those reported across Africa except North Africa. The major haplotypes in CYP2B6 rs3745274 and CYP2B6 rs2279343 were represented by GA (60.24%) followed by TG (35.36%). We noted a strong linkage disequilibrium between CYP2B6 rs3745274 and CYP2B6 rs2279343 with D'â=â0.91 and r2â=â0.9. The frequencies of the genotypic combinations were 43.5% (GT/AG), 37.3% (GG/AA) and 11.5% (TT/GG) in the combination of CYP2B6-rs3745274 and CYP2B6-rs2279343; 26.8% (GT/CC), 25.4%, (GT/CT), 17.2% and GG/CT in the combination CYP2B6-rs3745274-CYP3A4-rs2740574; 26.8% (AG/CC), 23.9% (AA/CC), 19.1% (AG/CT), and 11% (AA/CT) in the combination CYP2B6-rs2279343-CYP3A4-rs2740574, respectively. The most common triple genotype was GT/AG/CC with 24.9%, followed by GG/AA/CC with 23.9%, GT/AG/CT with 16.7%, and GG/AA/CT with 10%. Our results provide new insights into the distribution of these pharmacogenetically relevant genes in the Malian population. Moreover, these data will be useful for studies of individual genetic variability to drugs and genetic predisposition to diseases.
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Alelos , Genótipo , Haplótipos/genética , Adolescente , Adulto , Idoso , Citocromo P-450 CYP2B6/genética , Citocromo P-450 CYP3A/genética , Feminino , Humanos , Malásia/etnologia , Masculino , Pessoa de Meia-Idade , Farmacogenética/métodosRESUMO
OBJECTIVES: Breast cancer is the most prevalent cancer and the second leading cause of cancer-related deaths among women after cervical cancer in much of sub-Saharan Africa. This study aims to examine the prevalence and sociodemographic-socioeconomic factors associated with breast cancer screening among women of reproductive age in sub-Saharan Africa. DESIGN: A weighted population-based cross-sectional study using Demographic and Health Surveys (DHS) data. We used all available data on breast cancer screening from the DHS for four sub-Saharan African countries (Burkina Faso, Ivory Coast, Kenya and Namibia). Breast cancer screening was the outcome of interest for this study. Multivariable Poisson regression was used to identify independent factors associated with breast cancer screening. SETTING: Four countries participating in the DHS from 2010 to 2014 with data on breast cancer screening. PARTICIPANTS: Women of reproductive age 15-49 years (N=39 646). RESULTS: The overall prevalence of breast cancer screening was only 12.9% during the study period, ranging from 5.2% in Ivory Coast to 23.1% in Namibia. Factors associated with breast cancer screening were secondary/higher education with adjusted prevalence ratio (adjusted PR)=2.33 (95% CI: 2.05 to 2.66) compared with no education; older participants, 35-49 years (adjusted PR=1.73, 95% CI : 1.56 to 1.91) compared with younger participants 15-24 years; health insurance coverage (adjusted PR=1.57, 95% CI: 1.47 to 1.68) compared with those with no health insurance and highest socioeconomic status (adjusted PR=1.33, 95% CI : 1.19 to 1.49) compared with lowest socioeconomic status. CONCLUSION: Despite high breast cancer mortality rates in sub-Saharan Africa, the prevalence of breast cancer screening is substantially low and varies gradually across countries and in relation to factors such as education, age, health insurance coverage and household wealth index level. These results highlight the need for increased efforts to improve the uptake of breast cancer screening in sub-Saharan Africa.
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Neoplasias da Mama , Detecção Precoce de Câncer , Adolescente , Adulto , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/epidemiologia , Burkina Faso/epidemiologia , Côte d'Ivoire/epidemiologia , Estudos Transversais , Detecção Precoce de Câncer/estatística & dados numéricos , Feminino , Humanos , Quênia/epidemiologia , Pessoa de Meia-Idade , Namíbia/epidemiologia , Prevalência , Adulto JovemRESUMO
Bioinformatics and data science research have boundless potential across Africa due to its high levels of genetic diversity and disproportionate burden of infectious diseases, including malaria, tuberculosis, HIV and AIDS, Ebola virus disease, and Lassa fever. This work lays out an incremental approach for reaching underserved countries in bioinformatics and data science research through a progression of capacity building, training, and research efforts. Two global health informatics training programs sponsored by the Fogarty International Center (FIC) were carried out at the University of Sciences, Techniques and Technologies of Bamako, Mali (USTTB) between 1999 and 2011. Together with capacity building efforts through the West Africa International Centers of Excellence in Malaria Research (ICEMR), this progress laid the groundwork for a bioinformatics and data science training program launched at USTTB as part of the Human Heredity and Health in Africa (H3Africa) initiative. Prior to the global health informatics training, its trainees published first or second authorship and third or higher authorship manuscripts at rates of 0.40 and 0.10 per year, respectively. Following the training, these rates increased to 0.70 and 1.23 per year, respectively, which was a statistically significant increase (p < 0.001). The bioinformatics and data science training program at USTTB commenced in 2017 focusing on student, faculty, and curriculum tiers of enhancement. The program's sustainable measures included institutional support for core elements, university tuition and fees, resource sharing and coordination with local research projects and companion training programs, increased student and faculty publication rates, and increased research proposal submissions. Challenges reliance of high-speed bandwidth availability on short-term funding, lack of a discounted software portal for basic software applications, protracted application processes for United States visas, lack of industry job positions, and low publication rates in the areas of bioinformatics and data science. Long-term, incremental processes are necessary for engaging historically underserved countries in bioinformatics and data science research. The multi-tiered enhancement approach laid out here provides a platform for generating bioinformatics and data science technicians, teachers, researchers, and program managers. Increased literature on bioinformatics and data science training approaches and progress is needed to provide a framework for establishing benchmarks on the topics.