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Epidemiological and mechanistic evidence on the causative role of human papillomaviruses (HPV) in esophageal squamous cell carcinoma (ESCC) is unclear. We retrieved alcohol- and formalin-fixed paraffin-embedded ESCC tissues from 133 patients seropositive for antibodies against HPV early proteins, from high-incidence ESCC regions: South Africa, China and Iran. With rigorous care to prevent nucleic acid contamination, we analyzed these tissues for the presence of 51 mucosotropic human alpha-papillomaviruses by two sensitive, broad-spectrum genotyping methods, and for the markers of HPV-transformed phenotype: (i) HPV16/18 viral loads by quantitative real-time PCR, (ii) type-specific viral mRNA by E6*I/E6 full-length RT-PCR assays and (iii) expression of cellular protein p16(INK4a). Of 118 analyzable ESCC tissues, 10 (8%) were positive for DNA of HPV types: 16 (4 tumors); 33, 35, 45 (1 tumor each); 11 (2 tumors) and 16, 70 double infection (1 tumor). Inconsistent HPV DNA+ findings by two genotyping methods and negativity in qPCR indicated very low viral loads. A single HPV16 DNA+ tumor additionally harbored HPV16 E6*I mRNA but was p16(INK4a) negative (HPV16 E1 seropositive patient). Another HPV16 DNA+ tumor from an HPV16 E6 seropositive patient showed p16(INK4a) upregulation but no HPV16 mRNA. In the tumor tissues of these serologically preselected ESCC patients, we did not find consistent presence of HPV DNA, HPV mRNA or p16(INK4a) upregulation. These results were supported by a meta-analysis of 14 other similar studies regarding HPV-transformation of ESCC. Our study does not support the etiological role of the 51 analyzed mucosotropic HPV types in the ESCC carcinogenesis.
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Carcinogénesis/genética , Carcinoma de Células Escamosas/virología , Neoplasias Esofágicas/virología , Papillomavirus Humano 16/patogenicidad , Papillomavirus Humano 18/patogenicidad , Anciano , Carcinoma de Células Escamosas/epidemiología , Carcinoma de Células Escamosas/genética , China , Neoplasias Esofágicas/epidemiología , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas de Esófago , Femenino , Genotipo , Papillomavirus Humano 16/genética , Papillomavirus Humano 18/genética , Humanos , Irán , Masculino , Persona de Mediana Edad , Proteínas Oncogénicas Virales/genética , Proteínas Represoras/genética , SudáfricaRESUMEN
Cancer is projected to become a leading cause of morbidity and mortality in low-income and middle-income countries in the future. However, cancer incidence in South Africa is largely under-reported because of a lack of nationwide cancer surveillance networks. We describe present cancer surveillance activities in South Africa, and use the International Agency for Research on Cancer framework to propose the development of four population-based cancer registries in South Africa. These registries will represent the ethnic and geographical diversity of the country. We also provide an update on a cancer surveillance pilot programme in the Ekurhuleni Metropolitan District, and the successes and challenges in the implementation of the IARC framework in a local context. We examine the development of a comprehensive cancer surveillance system in a middle-income country, which might serve to assist other countries in establishing population-based cancer registries in a resource-constrained environment.
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Población Negra , Países en Desarrollo , Neoplasias/etnología , Vigilancia de la Población/métodos , Sistema de Registros , Adolescente , Adulto , Distribución por Edad , Factores de Edad , Niño , Preescolar , Países en Desarrollo/economía , Femenino , Humanos , Incidencia , Lactante , Recién Nacido , Masculino , Neoplasias/diagnóstico , Neoplasias/economía , Neoplasias/mortalidad , Neoplasias/terapia , Pronóstico , Desarrollo de Programa , Evaluación de Programas y Proyectos de Salud , Distribución por Sexo , Factores Sexuales , Sudáfrica/epidemiología , Factores de Tiempo , Adulto JovenRESUMEN
BACKGROUND: HIV infection is a known risk factor for cancer but little is known about HIV testing patterns and the burden of HIV infection in cancer patients. We did a cross-sectional analysis to identify predictors of prior HIV testing and to quantify the burden of HIV in black cancer patients in Johannesburg, South Africa. METHODS: The Johannesburg Cancer Case-control Study (JCCCS) recruits newly-diagnosed black cancer patients attending public referral hospitals for oncology and radiation therapy in Johannesburg . All adult cancer patients enrolled into the JCCCS from November 2004 to December 2009 and interviewed on previous HIV testing were included in the analysis. Patients were independently tested for HIV-1 using a single ELISA test . The prevalence of prior HIV testing, of HIV infection and of undiagnosed HIV infection was calculated. Multivariate logistic regression models were fitted to identify factors associated with prior HIV testing. RESULTS: A total of 5436 cancer patients were tested for HIV of whom 1833[33.7% (95% CI=32.5-35.0)] were HIV-positive. Three-quarters of patients (4092 patients) had ever been tested for HIV. The total prevalence of undiagnosed HIV infection was 11.5% (10.7-12.4) with 34% (32.0-36.3) of the 1833 patients who tested HIV-positive unaware of their infection. Men >49 years [OR 0.49(0.39-0.63)] and those residing in rural areas [OR 0.61(0.39-0.97)] were less likely to have been previously tested for HIV. Men with at least a secondary education [OR 1.79(1.11-2.90)] and those interviewed in recent years [OR 4.13(2.62 - 6.52)] were likely to have prior testing. Women >49 years [OR 0.33(0.27-0.41)] were less likely to have been previously tested for HIV. In women, having children <5 years [OR 2.59(2.04-3.29)], hormonal contraceptive use [OR 1.33(1.09-1.62)], having at least a secondary education [OR:2.08(1.45-2.97)] and recent year of interview [OR 6.04(4.45-8.2)] were independently associated with previous HIV testing. CONCLUSIONS: In a study of newly diagnosed black cancer patients in Johannesburg, over a third of HIV-positive patients were unaware of their HIV status. In South Africa black cancer patients should be targeted for opt-out HIV testing.
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Infecciones por VIH/diagnóstico , VIH-1 , Linfoma no Hodgkin/virología , Sarcoma de Kaposi/virología , Actitud Frente a la Salud , Población Negra , Estudios de Casos y Controles , Costo de Enfermedad , Estudios Transversales , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/epidemiología , Humanos , Linfoma no Hodgkin/epidemiología , Masculino , Tamizaje Masivo , Persona de Mediana Edad , Prevalencia , Sarcoma de Kaposi/epidemiología , SudáfricaRESUMEN
The C-type lectins DC-SIGN and L-SIGN are important pathogen-recognition receptors of the human innate immune system. Both lectins have been shown to interact with a vast range of infectious agents, including Mycobacterium tuberculosis, the etiologic agent of tuberculosis in humans. In addition, DC-SIGN and L-SIGN possess a neck region, made up of a variable number of 23 amino acid tandem repeats, which plays a crucial role in the tetramerization of these proteins and support of the carbohydrate recognition domain. The length of the neck region, which shows variable levels of polymorphism, can critically influence the pathogen binding properties of these two receptors. We therefore investigated the impact of the DC-SIGN and L-SIGN neck-region length variation on the outcome of tuberculosis by screening this polymorphism in a large cohort of Coloured South African origin. The analyses of 711 individuals, including 351 tuberculosis patients and 360 healthy controls, revealed that none of the DC-SIGN and L-SIGN neck-region variants or genotypes seems to influence the individual susceptibility to develop tuberculosis.
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Moléculas de Adhesión Celular/genética , Lectinas Tipo C/genética , Polimorfismo de Longitud del Fragmento de Restricción , Receptores de Superficie Celular/genética , Tuberculosis Pulmonar/genética , Adulto , Moléculas de Adhesión Celular/metabolismo , Estudios de Cohortes , Susceptibilidad a Enfermedades , Femenino , Humanos , Lectinas Tipo C/metabolismo , Masculino , Mycobacterium tuberculosis/metabolismo , Receptores de Superficie Celular/metabolismo , Sudáfrica , Tuberculosis Pulmonar/patologíaRESUMEN
BACKGROUND: Tuberculosis, which is caused by Mycobacterium tuberculosis, remains one of the leading causes of mortality worldwide. The C-type lectin DC-SIGN is known to be the major M. tuberculosis receptor on human dendritic cells. We reasoned that if DC-SIGN interacts with M. tuberculosis, as well as with other pathogens, variation in this gene might have a broad range of influence in the pathogenesis of a number of infectious diseases, including tuberculosis. METHODS AND FINDINGS: We tested whether polymorphisms in CD209, the gene encoding DC-SIGN, are associated with susceptibility to tuberculosis through sequencing and genotyping analyses in a South African cohort. After exclusion of significant population stratification in our cohort, we observed an association between two CD209 promoter variants (-871G and -336A) and decreased risk of developing tuberculosis. By looking at the geographical distribution of these variants, we observed that their allelic combination is mainly confined to Eurasian populations. CONCLUSIONS: Our observations suggest that the two -871G and -336A variants confer protection against tuberculosis. In addition, the geographic distribution of these two alleles, together with their phylogenetic status, suggest that they may have increased in frequency in non-African populations as a result of host genetic adaptation to a longer history of exposure to tuberculosis. Further characterization of the biological consequences of DC-SIGN variation in tuberculosis will be crucial to better appreciate the role of this lectin in interactions between the host immune system and the tubercle bacillus as well as other pathogens.
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Moléculas de Adhesión Celular/genética , Lectinas Tipo C/genética , Mycobacterium tuberculosis/patogenicidad , Receptores de Superficie Celular/genética , Tuberculosis Pulmonar/genética , Tuberculosis Pulmonar/fisiopatología , Adulto , Población Negra/genética , Estudios de Casos y Controles , Moléculas de Adhesión Celular/fisiología , Células Dendríticas , Femenino , Predisposición Genética a la Enfermedad , Humanos , Lectinas Tipo C/fisiología , Masculino , Persona de Mediana Edad , Filogenia , Polimorfismo de Nucleótido Simple , Regiones Promotoras Genéticas , Receptores de Superficie Celular/fisiología , Factores de Riesgo , SudáfricaRESUMEN
The impact of tuberculosis (TB) is considerably lower than one may expect, since in the absence of immunosuppression, fewer than 10% of infected individuals will develop active disease. The relatively low proportion of individuals who progress to active disease after infection can probably be ascribed to innate resistance in most infected individuals, since vaccination using BCG or a previous episode of TB does not work reliably or effectively to confer protection in high burden parts of the world. Innate factors affecting resistance or susceptibility can be modulated by the environment and such external influences cannot be ignored. Specifically, we will address bacterial variability as well as environmental factors such as diet, smoking, helminths and hormones. We will also discuss host genes that may be involved in susceptibility or resistance at various stages of infection or disease. The discovery of as yet unknown genes impacting on TB susceptibility or disease course may lead to new insights into mechanisms of disease and novel therapies. With adaptive immunity being of little value and good TB control programmes being rare, innate resistance is still our best defence against this
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Tuberculosis/epidemiología , Tuberculosis/genética , Susceptibilidad a Enfermedades , Ambiente , Humanos , Mycobacterium tuberculosis/fisiología , Fenómenos Fisiológicos de la Nutrición , Caracteres Sexuales , Tuberculosis/microbiologíaRESUMEN
Little is known about the incidence patterns of hematologic malignancies in Sub-Saharan Africa, including South Africa. We estimated incidence rates of pathology-confirmed adult cases of leukemia, myeloma and related diseases (myeloma), Hodgkin lymphoma (HL), and non-Hodgkin lymphoma (NHL) reported to the National Cancer Registry of South Africa (NCR) between 2000 and 2006, by age, gender, and population group (Black, White, Coloured, Asian/Indian). Gender-specific age-standardized rates were calculated overall and by population group and incidence rate ratios (IRRs) were estimated using Poisson regression models. Between 2000 and 2006, there were 14662 cases of leukemia, myeloma, HL, and NHL reported to the registry. Incidence rates of reported hematologic malignancies were generally 20-50% higher among males than females. Our analyses suggested marked differences in the rates of reported hematologic malignancies by population group which were most pronounced when comparing the White versus Black population groups (IRRs ranging from 1.6 for myeloma to 3.8 for HL for males and females combined). Challenges related to diagnosis and reporting of cancers may play a role in the patterns observed by population group while the set-up of the NCR (pathology-based) could lead to some degree of under-ascertainment in all groups. This is the first country-wide report of the incidence of hematologic malignancies in South Africa. Despite challenges, it is important to analyze and report available national cancer incidence data to raise awareness of the cancer burden and to characterize patterns by demographic characteristics so as ultimately to improve the provision of cancer-related health care.
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Neoplasias Hematológicas/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Neoplasias Hematológicas/historia , Historia del Siglo XXI , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Vigilancia de la Población , Sistema de Registros , Sudáfrica/epidemiología , Adulto JovenRESUMEN
[This corrects the article DOI: 10.1155/2014/419801.].
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Prostate cancer is one of the most common male cancers globally; however little is known about prostate cancer in Africa. Incidence data for prostate cancer in South Africa (SA) from the pathology based National Cancer Registry (1986-2006) and data on mortality (1997-2009) from Statistics SA were analysed. World standard population denominators were used to calculate age specific incidence and mortality rates (ASIR and ASMR) using the direct method. Prostate cancer was the most common male cancer in all SA population groups (excluding basal cell carcinoma). There are large disparities in the ASIR between black, white, coloured, and Asian/Indian populations: 19, 65, 46, and 19 per 100 000, respectively, and ASMR was 11, 7, 52, and 6 per 100 000, respectively. Prostate cancer was the second leading cause of cancer death, accounting for around 13% of male deaths from a cancer. The average age at diagnosis was 68 years and 74 years at death. For SA the ASIR increased from 16.8 in 1986 to 30.8 in 2006, while the ASMR increased from 12.3 in 1997 to 16.7 in 2009. There has been a steady increase of incidence and mortality from prostate cancer in SA.
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Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal tumours of the digestive tract. Pathogenesis is linked to activating mutations identified in two proto-oncogenes, v-kit Hardy/Zuckerman 4 feline sarcoma viral oncogene homologue KIT (KIT) and the platelet-derived growth factor α (PDGFRα). In addition, these mutations affect response to treatment with tyrosine kinase inhibitors. In the present study, we report on the molecular characterisation of GISTs in the South African population. Tumour DNA was extracted from 46 GIST samples, followed by cycle sequencing of KIT exons 11, 13 and 17 and PDGFRα exons 12, 14 and 18. Fragment length analysis was used to detect a 6-bp duplication in KIT exon 9. Wild-type duplications were analysed further by PCR and sequencing of additional KIT and PDGFRα exons was performed. Overall, 78.3% of the samples had a mutation in KIT or PDGFRα. Of these, mutations were detected in KIT exon 11 (88.9%), PDGFRα exon 18 (8.3%) and KIT exon 9 (2.8%). Mutations varied from simple substitutions and duplications to large deletions (some with nucleotide insertions) resulting in missense mutations. In addition, seven single nucleotide polymorphisms were detected in 17 patients, one of which appears novel. The incidence of mutations in KIT exon 11 and PDGFRα exon 18 is consistent with the literature, however, the low incidence of KIT exon 9 mutations detected was unexpected. In contrast to previous western and Asian studies, this mutation appears to be rare in the South African population. The present study contributes to the molecular understanding of GISTs in the South African population.
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We present common cytogenetic features in the largest cohort of plasmablastic lymphoma (PBL) of the oral cavity published to date. This cohort included 45 patients, 32 of whom had a known HIV status, of which 31 were HIV positive. Ninety eight per cent of all PBL cases were known to be EBV positive. In line with previous studies, we found that rearrangements of the MYC gene was the most common genetic abnormality seen in 60% of cases with the immunoglobulin heavy chain (IGH) locus as a partner in 51% of cases. Additional complex genetic aberrations were frequent, in particular, an increased copy number of the CCND1 gene was seen in 41% of cases with true amplification of CCND1 in 15% of cases. Aneuploidy was also observed for the BCL6 gene in 28% of cases. Interestingly, rearrangements of both IGH genes were detected in 16% of cases with t(14;18) and t(11;14) respectively involved in conjunction with a t(8;14) in two cases. These bi-allelic IGH rearrangements have not been described before in oral PBL. Our results reinforce the notion that EBV infection and MYC rearrangements are important events in the pathogenesis of oral PBL. The genetic diversity and complexity observed in these cases, underlines the importance to genetically characterise PBL patients at presentation as this may inform the choice of more effective treatment modalities.
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Infecciones por Virus de Epstein-Barr/genética , Linfoma Relacionado con SIDA/genética , Neoplasias de la Boca/genética , Adulto , Aneuploidia , Estudios de Cohortes , Ciclina D1/genética , Proteínas de Unión al ADN/genética , Femenino , Reordenamiento Génico , Genes myc/genética , Humanos , Cadenas Pesadas de Inmunoglobulina/genética , Hibridación Fluorescente in Situ/métodos , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/virología , Proteínas Proto-Oncogénicas c-bcl-6RESUMEN
The recent introduction of fluorescent bead-based technology, allowing the measurement of multiples analytes in a single 25-50 microl sample has revolutionized the study of cytokine responses. However, such multiplex approaches may compromise the ability of these assays to accurately measure actual cytokine levels. This study evaluates the performance of three commercially available multiplex cytokine fluorescent bead-based immunoassays (Bio-Rad's Cytokine 17-plex kit; LINCO Inc's 29-plex kit; and RnD System's Fluorokine-Multi Analyte Profiling (MAP) base kit A and B). The LINCO Inc kit was found to be the most sensitive assay for measuring concentrations of multiple recombinant cytokines in samples that had been spiked with serial dilutions of the standard provided by the manufacturer, followed respectively by the RnD Fluorokine-(MAP) and Bio-Rad 17-plex kits. A positive correlation was found in the levels of IFN-gamma measured in antigen stimulated whole blood culture supernatants by the LINCO Inc 29-plex, RnD Fluorokine-(MAP) and RnD system IFN-gamma Quantikine ELISA kits across a panel of controls and stimulated samples. Researchers should take the limitation of such multiplexed assays into account when planning experiments and the most appropriate use for these tests may currently be as screening tools for the selection of promising markers for analysis by more sensitive techniques.