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1.
BMC Infect Dis ; 24(1): 356, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38539128

RESUMO

BACKGROUND: The burden of cervical cancer in Ghana is high due to a lack of a national screening and vaccination program. Geographical variations in high-risk Human Papilloma Virus incidence and type should be considered for vaccine improvement and screening in LMICs. METHODS: A descriptive, multi-center cross-sectional study with purposive sampling of cases with cervical cancer diagnosed from January 2012 through to December 2018 was employed relying on archived Formalin Fixed Paraffin Embedded (FFPE) tissues from four (4) Teaching Hospitals. Cervical cancers were assessed for histopathological features following WHO guidelines. In addition, the novel Tumour Budding and Nest Size Grade (TBNS) for SCC, SILVA pattern of invasion for EAC and Tumour Infiltrating Lymphocytes (TILs) were assessed. High Risk HPV testing was performed using an isothermal, multiplex nucleic acid amplification method from ATILA biosystem (Mountain View California, USA). The FFPE blocks were tested for 15 hrHPV genotypes. Results were analyzed using SPSS v.26.0, with descriptive statistics and cross-tabulation and chi-square tests done with significance established at p < 0.05. RESULTS: A total of 297 cases were identified for the study with ages ranging from 20 to 95 years. The peak age group for cervical cancer was 46 to 55 years. For those tested, hrHPV positivity rate was 85.4% [EAC (84.6%) and SCC (85.6%)]. The top five hrHPV serotypes for both histological cancers were 59 (40.0%), 35 (32.0%), 18 (30.0%), 16 (15.0%), and 33 (10.0%) respectively. Approximately, 58.2% of infections were multiple. Single hrHPV infections were mostly caused by hrHPV 59 (28.9%), and 16 (26.3%). TBNS grade for SCC, SILVA pattern of invasion for EAC and TILs did not show any statistically significant relationship with hrHPV. CONCLUSION: We affirm reported differences in hrHPV types associated with cervical cancer in Ghana with hrHPV types such as 59, 35, and 33 forming a significant proportion of hrHPV types associated with cervical cancer. This difference in hrHPV types should guide vaccine improvement and triaging of hrHPV positives. Though multiple infections are more common, some hrHPV types such as hrHPV 16 and 59 are responsible for most single infections associated with cervical cancer. Simple haematoxylin and eosin-based morphological assessments can improve the prognostication of patients with cervical cancer.


Assuntos
Infecções por Papillomavirus , Neoplasias do Colo do Útero , Vacinas , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/patologia , Estudos Transversais , Gana/epidemiologia , Genótipo , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/complicações , Papillomaviridae/genética , Detecção Precoce de Câncer/métodos
2.
Prostate ; 81(16): 1402-1410, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34529278

RESUMO

BACKGROUND: Native African men (NAM) experience a disproportionate burden of prostate cancer (PCa) and have higher mortality rates compared to European American men (EAM). While socioeconomic status has been implicated as a driver of this disparity, little is known about the genomic mechanisms and distinct biological pathways that are associated with PCa of native men of African origin. METHODS: To understand biological factors that contribute to this disparity we utilized a total of 406 multi-institutional localized PCa samples, collected by Men of African Descent and Carcinoma of the Prostate biospecimen network and Moffitt Cancer Center/University of Pennsylvania Health science system. We performed comparative genomics and immunohistochemistry to identify the biomarkers that are highly enriched in NAM from west Africa and compared them with African American Men (AAM) and EAM. Quantified messenger RNA expression and Median H scores based on immune reactivity of staining cells, were compared using Mann Whitney test. For gene expression analysis, p values were further adjusted for multiple comparisons using false discovery rates. RESULTS: Immunohistochemical analysis on selected biomarkers showed a consistent association between ETS related gene (ERG) status and race with 83% of NAM exhibiting tumors that lacked TMPRSS2-ERG translocation (ERGnegative ) as compared to AAM (71%) and EAM (52%). A higher proportion of NAM (29%) were also found to be double negative (ERGnegative and PTENLoss ) as compared to AAM (6%) and EAM (7%). NAM tumors had significantly higher immunoreactivity (H-score) for PSMA, and EZH2, whereas they have lower H-score for PTEN, MYC, AR, RB and Racemase, (all p < .05). Comparative genomics revealed that NAM had significant transcriptomic variability in AR-activity score. In pathways enrichment analysis NAM tumors exhibited the enrichment of proinflammatory pathways including cytokine, interleukins, inflammatory response, and nuclear factor kappa B signaling. CONCLUSIONS: Prostate tumors in NAM are genomically distinct and are characterized by the dysregulation of several biomarkers. Furthermore, these tumors are also highly enriched for the major proinflammatory pathways. These distinct biological features may have implications for diagnosis and response to targeted therapy among Black men, globally.


Assuntos
Carcinoma , Canais de Potássio Éter-A-Go-Go/genética , Neoplasias da Próstata , Serina Endopeptidases/genética , Bancos de Espécimes Biológicos , População Negra , Carcinoma/etnologia , Carcinoma/genética , Carcinoma/patologia , Perfilação da Expressão Gênica/métodos , Perfilação da Expressão Gênica/estatística & dados numéricos , Testes Genéticos/métodos , Genômica , Gana/epidemiologia , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/etnologia , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Senegal/epidemiologia , Transdução de Sinais/genética , Estados Unidos/etnologia , População Branca
4.
Ghana Med J ; 58(1): 73-77, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38957277

RESUMO

Objective: The study aimed to detect the presence of Helicobacter pylori infection in children using two investigative methods: the rapid urease test and histological methods. It also examined the relationship between socioeconomic status and Helicobacter pylori infection. Design: This was a cross-sectional study conducted in the paediatric theatre at Korle Bu Teaching Hospital in Accra, Ghana. Participants: Children who were scheduled for upper gastrointestinal endoscopy were recruited into the study. Main outcome measures: The presence of Helicobacter pylori in gastric biopsies was measured using a rapid urease test and histology. Results: Seventy-three children aged 2 years to 16 years were seen during the period. Both tests were positive at the same time in 36 (49.3%) out of the 73 children (p<0.0001). The positivity rates for the rapid urease test and histology were 57.5% and 53.4 %, respectively. Significant predictors of the histology presence of H. pylori were a large household size of at least 6 members (AOR: 4.03; p<0.013) and the presence of pets at home (AOR: 3.23; p<0.044). Conclusions: Substantial agreement was found between the rapid urease test and histology examination of gastric biopsies for the presence of H. pylori. Children from large households and those with pets at home appear to have increased odds of having H. pylori infection of the gastric mucosa. Funding: None declared.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Urease , Humanos , Infecções por Helicobacter/diagnóstico , Helicobacter pylori/isolamento & purificação , Criança , Estudos Transversais , Masculino , Urease/análise , Feminino , Pré-Escolar , Adolescente , Gana/epidemiologia , Biópsia , Fatores Socioeconômicos , Mucosa Gástrica/patologia , Mucosa Gástrica/microbiologia
5.
J Pediatr Surg ; 59(7): 1342-1348, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38589272

RESUMO

BACKGROUND: Between 2005 and 2014, Ghana's Wilms tumor (WT) 2-year disease-free survival of 44% trailed behind that of high-income countries. This study aimed to uncover social determinants of health leading to preventable WT death in Ghana. METHODS: WT patient records (2014-2022) at Korle-Bu Teaching Hospital (KBTH; Ghana) were reviewed retrospectively. Demographics, clinical course, tumor characteristics, and survival were evaluated using t-tests, Pearson Chi-square, and multivariate Cox logistic regression. RESULTS: Of 127 patients identified, 65 were female. Median age was 44 months [IQR 25-66]. Forty-eight patients (38%) presented with distant metastasis (75% lung, 25% liver), which associated with hypoalbuminemia (p = 0.009), caregiver informal employment (p = 0.04), and larger tumors (p = 0.002). Despite neoadjuvant chemotherapy shrinking 84% of tumors, larger initial size associated with incomplete resection (p = 0.046). Of 110 nephrectomies, 31 patients had residual disease, negatively impacting survival (p = 2.7 × 10-5). Twenty-two patients (17%) abandoned treatment (45% before nephrectomy; 55% after nephrectomy), with seven patients ultimately lost to follow-up (LTFU). Decedents represented 43% of stage IV patients compared to 28% in other stages. Event-free survival (EFS) was 60% at 4 years with overall survival (OS) at 67%. CONCLUSIONS: Although Ghana's WT survival has improved, informal employment and distance from KBTH predisposed patients to delayed referral, greater tumor burden, hypoalbuminemia, and lower survival. TYPE OF STUDY: Prognosis Study. LEVEL OF EVIDENCE: II.


Assuntos
Neoplasias Renais , Nefrectomia , Tumor de Wilms , Humanos , Tumor de Wilms/terapia , Tumor de Wilms/mortalidade , Tumor de Wilms/patologia , Tumor de Wilms/cirurgia , Gana/epidemiologia , Feminino , Masculino , Estudos Retrospectivos , Pré-Escolar , Neoplasias Renais/terapia , Neoplasias Renais/patologia , Neoplasias Renais/mortalidade , Neoplasias Renais/cirurgia , Carga Tumoral , Lactente , Criança , Intervalo Livre de Doença , Determinantes Sociais da Saúde , Terapia Neoadjuvante/estatística & dados numéricos
6.
JCO Glob Oncol ; 10: e2300403, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38870437

RESUMO

PURPOSE: Prostate cancer disproportionately affects men of African descent, yet their representation in tissue-based studies is limited. This multinational, multicenter pilot study aims to establish the groundwork for collaborative research on prostate cancer in sub-Saharan Africa. METHODS: The Men of African Descent and Carcinoma of the Prostate network formed a pathologist working group representing eight institutions in five African countries. Formalin-fixed paraffin-embedded prostate tissue specimens were collected from Senegal, Nigeria, and Ghana. Histology slides were produced and digitally scanned. A central genitourinary pathologist (P.L.) and eight African general pathologists reviewed anonymized digital whole-slide images for International Society of Urological Pathology grade groups and other pathologic parameters. Discrepancies were re-evaluated, and consensus grading was assigned. A virtual training seminar on prostate cancer grading was followed by a second assessment on a subcohort of the same tissue set. RESULTS: Of 134 tissue blocks, 133 had evaluable tissue; 13 lacked cancer evidence, and four were of insufficient quality. Post-training, interobserver agreement for grade groups improved to 56%, with a median Cohen's quadratic weighted kappa of 0.83 (mean, 0.74), compared with an initial 46% agreement and a quadratic weighted kappa of 0.77. Interobserver agreement between African pathologist groups was 40%, with a quadratic weighted kappa of 0.66 (95% CI, 0.51 to 0.76). African pathologists tended to overgrade (36%) more frequently than undergrade (18%) compared with the reference genitourinary pathologist. Interobserver variability tended to worsen with a decrease in tissue quality. CONCLUSION: Tissue-based studies on prostate cancer in men of African descent are essential for a better understanding of this common disease. Standardized tissue handling protocols are crucial to ensure good tissue quality and data. The use of digital slide imaging can enhance collaboration among pathologists in multinational, multicenter studies.


Assuntos
Neoplasias da Próstata , Masculino , Humanos , Neoplasias da Próstata/patologia , África Subsaariana , Projetos Piloto , Gradação de Tumores
7.
Respirol Case Rep ; 11(10): e01225, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37771847

RESUMO

Adult-onset asthma is extremely variable in its phenotypic presentation and has gained notoriety for the overall poorer treatment outcomes even on standard asthma therapy. Tracheal tumours are rare but when present, exhibit asthma-like phenomenon in adult patients posing great diagnostic challenges. We report two adult patients with tracheal adenoid cystic tumours who were initially treated for adult-onset asthma. Patient 1, a 45-year-old man was diagnosed and managed for adult-onset asthma over a 12 months period without satisfactory control of his symptoms. Following a late episode of hemoptysis, a chest Computed Tomography (CT) scan done revealed an occluding tracheal tumour. Patient 2 is a 28-year-old female who was diagnosed with adult-onset asthma for over 2 years with poor symptom control despite optimal asthma therapy. She developed cough-induced subcutaneous emphysema for which a chest CT scan revealed a tracheal mass. The patient had surgery with incomplete resection of tumour and adjuvant radiotherapy.

8.
Res Sq ; 2023 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-37886553

RESUMO

Men of African descent have the highest prostate cancer (CaP) incidence and mortality rates, yet the genetic basis of CaP in African men has been understudied. We used genomic data from 3,963 CaP cases and 3,509 controls recruited in Ghana, Nigeria, Senegal, South Africa, and Uganda, to infer ancestry-specific genetic architectures and fine-mapped disease associations. Fifteen independent associations at 8q24.21, 6q22.1, and 11q13.3 reached genome-wide significance, including four novel associations. Intriguingly, multiple lead SNPs are private alleles, a pattern arising from recent mutations and the out-of-Africa bottleneck. These African-specific alleles contribute to haplotypes with odds ratios above 2.4. We found that the genetic architecture of CaP differs across Africa, with effect size differences contributing more to this heterogeneity than allele frequency differences. Population genetic analyses reveal that African CaP associations are largely governed by neutral evolution. Collectively, our findings emphasize the utility of conducting genetic studies that use diverse populations.

9.
Ecancermedicalscience ; 16: 1458, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36405938

RESUMO

Background: Non-Hodgkin lymphomas (NHLs) are a heterogeneous group of clonal lymphoid tumours originating from lymphocytes. They constitute about 90% of an estimated 3%-4% worldwide distribution of malignant lymphomas among various cancers. Despite the continuous rise and associated deaths, research on NHLs, and in particular the area of immunophenotypic spectrum is limited in Ghana and sub-Saharan Africa. Methods: A retrospective, descriptive study in which archived tissue blocks of histologically diagnosed NHLs at a tertiary hospital in Accra, Ghana, were used. Antigenic phenotypes were determined by immunohistochemistry. Results: A total of 66 cases of NHLs, with a mean age of 50.2 ± 16.1 years, were selected for the study. Among the targeted markers, cluster of differentiation 20 (CD20) was the most commonly expressed in 89.4% (59) cases. Immunohistochemistry studies revealed a greater proportion of B cell lymphomas of 89.4%. Five subtypes were successfully identified, of which diffuse large B cell lymphoma constitutes the predominant group (40.9%). A significant association was observed between phenotypic cell types and outcomes of NHLs (p = 0.011). Conclusion: Adult NHLs were mostly due to the malignant transformation of B cells with diffuse large B cell lymphoma being the commonest subtype. The present study therefore serves as preliminary data for further research towards the adoption of an improved treatment regimen and management of NHLs.

10.
IJID Reg ; 4: 75-84, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35813561

RESUMO

Objectives: This study sought to determine the genetic diversity and drug resistance profiles of Mycobacterium tuberculosis complex (MTBC) isolates from extrapulmonary tuberculosis (EPTB) patients in Ghana, and their associated immune responses. Methods: Spoligotyping was performed on 102 MTBC isolates from EPTB patients. Lineages/sub-lineages were assigned by comparing spoligotyping patterns primarily with the SITVIT2 database and subsequently with the TB-Lineage online tool for unknown isolates in SITVIT2. Drug susceptibility testing was performed using MGIT (BD BACTEC 960), Lowenstein-Jensen media (indirect proportion method), and GenoType MTBDRplus/MTBDRsl assays. Differential cytokine levels in the serum of 20 EPTB patients infected with MTBC lineage 4 were determined using the Luminex multiplex immunoassay. Results: Around 95% (97/102) of isolates were Mycobacterium tuberculosis, predominantly lineage 4 (95%; 92/97). Of the lineage 4 isolates, the majority were sub-lineage Cameroon (37%, 34/92). Prevalence was significantly higher in the 15-34 years age group among EPTB patients infected with lineage 4 strains (p = 0.024). Fifteen isolates were resistant to at least one anti-TB drug tested. Decreased levels of IL-1ß, IL-17A, and IFN-α were observed in individuals infected with Cameroon sub-lineages compared with other lineage 4 sub-lineages. Conclusions: Our study confirms Cameroon (SIT61) as the most common spoligotype causing human EPTB in Ghana, and that it is associated with decreased serum IL-1ß, IL-17A, and IFN-α.

11.
Heliyon ; 8(12): e12370, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36590545

RESUMO

Background: The detection of acid-fast bacilli in extrapulmonary tissue samples is challenging due to its paucibacillary nature. The present study assessed the utility of immunohistochemistry (IHC) using anti-Mycobacterium tuberculosis antibody (ab905) for detecting the presence of mycobacterial antigens in archived formalin-fixed paraffin-embedded (FFPE) tissues. Methods: FFPE tissues [surgical biopsies (n = 32) and post-mortem tissues (n = 8)] from clinically and histologically suggestive extrapulmonary tuberculosis (EPTB) cases at the Korle Bu Teaching Hospital, Accra, Ghana from 2015 to 2020 were stained with IHC (anti-Mycobacterium tuberculosis antibody) and Ziehl-Neelsen (ZN) stain. The staining outcomes of IHC and ZN were compared, and their sensitivity and specificity determined against histopathology as reference standard. Results: Lymph nodes were about 40% (16/40) of the samples analyzed. IHC stained positive in 43.8% (7/16) biopsies and 87.5% (4/5) post-mortem samples ranging from 43.8% (7/16) in lymph nodes to 80% (4/5) in gastrointestinal organs. The overall sensitivity for IHC was 52.50% (95% CI: 36.13%-68.49%) and 0% (95% CI: 0.00%-8.81%) for ZN. Specificity was 72.50% (95% CI: 56.11%-85.40%) and 75% (95% CI: 58.80-87.31%) for IHC and ZN respectively. Conclusions: IHC using anti-Mycobacterium tuberculosis antibody (ab905) can detect mycobacterial antigens in diverse range of paucibacillary extrapulmonary tissue sections. It is potentially a useful tool for the diagnosis of EPTB in FFPE tissues in a routine pathology laboratory.

12.
Genome Biol ; 23(1): 194, 2022 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-36100952

RESUMO

BACKGROUND: Genome-wide association studies do not always replicate well across populations, limiting the generalizability of polygenic risk scores (PRS). Despite higher incidence and mortality rates of prostate cancer in men of African descent, much of what is known about cancer genetics comes from populations of European descent. To understand how well genetic predictions perform in different populations, we evaluated test characteristics of PRS from three previous studies using data from the UK Biobank and a novel dataset of 1298 prostate cancer cases and 1333 controls from Ghana, Nigeria, Senegal, and South Africa. RESULTS: Allele frequency differences cause predicted risks of prostate cancer to vary across populations. However, natural selection is not the primary driver of these differences. Comparing continental datasets, we find that polygenic predictions of case vs. control status are more effective for European individuals (AUC 0.608-0.707, OR 2.37-5.71) than for African individuals (AUC 0.502-0.585, OR 0.95-2.01). Furthermore, PRS that leverage information from African Americans yield modest AUC and odds ratio improvements for sub-Saharan African individuals. These improvements were larger for West Africans than for South Africans. Finally, we find that existing PRS are largely unable to predict whether African individuals develop aggressive forms of prostate cancer, as specified by higher tumor stages or Gleason scores. CONCLUSIONS: Genetic predictions of prostate cancer perform poorly if the study sample does not match the ancestry of the original GWAS. PRS built from European GWAS may be inadequate for application in non-European populations and perpetuate existing health disparities.


Assuntos
Estudo de Associação Genômica Ampla , Neoplasias da Próstata , África Subsaariana/epidemiologia , Predisposição Genética para Doença , Humanos , Masculino , Neoplasias da Próstata/genética , Fatores de Risco
13.
Elife ; 112022 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-35801699

RESUMO

Background: We recently developed a multi-ancestry polygenic risk score (PRS) that effectively stratifies prostate cancer risk across populations. In this study, we validated the performance of the PRS in the multi-ancestry Million Veteran Program and additional independent studies. Methods: Within each ancestry population, the association of PRS with prostate cancer risk was evaluated separately in each case-control study and then combined in a fixed-effects inverse-variance-weighted meta-analysis. We further assessed the effect modification by age and estimated the age-specific absolute risk of prostate cancer for each ancestry population. Results: The PRS was evaluated in 31,925 cases and 490,507 controls, including men from European (22,049 cases, 414,249 controls), African (8794 cases, 55,657 controls), and Hispanic (1082 cases, 20,601 controls) populations. Comparing men in the top decile (90-100% of the PRS) to the average 40-60% PRS category, the prostate cancer odds ratio (OR) was 3.8-fold in European ancestry men (95% CI = 3.62-3.96), 2.8-fold in African ancestry men (95% CI = 2.59-3.03), and 3.2-fold in Hispanic men (95% CI = 2.64-3.92). The PRS did not discriminate risk of aggressive versus nonaggressive prostate cancer. However, the OR diminished with advancing age (European ancestry men in the top decile: ≤55 years, OR = 7.11; 55-60 years, OR = 4.26; >70 years, OR = 2.79). Men in the top PRS decile reached 5% absolute prostate cancer risk ~10 years younger than men in the 40-60% PRS category. Conclusions: Our findings validate the multi-ancestry PRS as an effective prostate cancer risk stratification tool across populations. A clinical study of PRS is warranted to determine whether the PRS could be used for risk-stratified screening and early detection. Funding: This work was supported by the National Cancer Institute at the National Institutes of Health (grant numbers U19 CA214253 to C.A.H., U01 CA257328 to C.A.H., U19 CA148537 to C.A.H., R01 CA165862 to C.A.H., K99 CA246063 to B.F.D, and T32CA229110 to F.C), the Prostate Cancer Foundation (grants 21YOUN11 to B.F.D. and 20CHAS03 to C.A.H.), the Achievement Rewards for College Scientists Foundation Los Angeles Founder Chapter to B.F.D, and the Million Veteran Program-MVP017. This research has been conducted using the UK Biobank Resource under application number 42195. This research is based on data from the Million Veteran Program, Office of Research and Development, and the Veterans Health Administration. This publication does not represent the views of the Department of Veteran Affairs or the United States Government.


Assuntos
Estudo de Associação Genômica Ampla , Neoplasias da Próstata , Fatores Etários , Estudos de Casos e Controles , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Herança Multifatorial , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/genética , Fatores de Risco , Estados Unidos/epidemiologia
14.
Case Rep Urol ; 2020: 8877695, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33005472

RESUMO

Idiopathic scrotal calcinosis is a rare condition, characterized by the idiopathic deposition of calcium in the scrotal dermis leading to the formation of a single nodule or multiple nodules of different sizes. Surgical excision of the nodules reduces symptoms and improves cosmesis. We present a case of idiopathic scrotal calcinosis that had an en bloc excision of scrotal skin nodules and primary closure of the scrotal skin. Handling each hemiscrotum as a separate entity and preserving the median raphe with its uninvolved skin improved the cosmesis. Reported outcomes of surgery were satisfactory with no postoperative complications. At 30 months of follow-up, the residual scrotal skin had regained its laxity and the scrotum its normal configuration. There is the risk of recurrence of the calcific nodules post excision, but these may be smaller in size and with regained scrotal configuration that could be amenable to excision with further preservation of the native scrotal skin.

15.
Cancer Res ; 80(13): 2956-2966, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32393663

RESUMO

Although prostate cancer is the leading cause of cancer mortality for African men, the vast majority of known disease associations have been detected in European study cohorts. Furthermore, most genome-wide association studies have used genotyping arrays that are hindered by SNP ascertainment bias. To overcome these disparities in genomic medicine, the Men of African Descent and Carcinoma of the Prostate (MADCaP) Network has developed a genotyping array that is optimized for African populations. The MADCaP Array contains more than 1.5 million markers and an imputation backbone that successfully tags over 94% of common genetic variants in African populations. This array also has a high density of markers in genomic regions associated with cancer susceptibility, including 8q24. We assessed the effectiveness of the MADCaP Array by genotyping 399 prostate cancer cases and 403 controls from seven urban study sites in sub-Saharan Africa. Samples from Ghana and Nigeria clustered together, whereas samples from Senegal and South Africa yielded distinct ancestry clusters. Using the MADCaP array, we identified cancer-associated loci that have large allele frequency differences across African populations. Polygenic risk scores for prostate cancer were higher in Nigeria than in Senegal. In summary, individual and population-level differences in prostate cancer risk were revealed using a novel genotyping array. SIGNIFICANCE: This study presents an Africa-specific genotyping array, which enables investigators to identify novel disease associations and to fine-map genetic loci that are associated with prostate and other cancers.


Assuntos
População Negra/genética , Predisposição Genética para Doença , Neoplasias/epidemiologia , Neoplasias/genética , Polimorfismo de Nucleotídeo Único , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/genética , Estudos de Casos e Controles , Estudos de Coortes , Loci Gênicos , Genética Populacional , Estudo de Associação Genômica Ampla , Humanos , Masculino , Neoplasias/classificação , Neoplasias da Próstata/classificação , Fatores de Risco , África do Sul/epidemiologia
16.
Am J Clin Oncol ; 42(12): 937-944, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31584456

RESUMO

PURPOSE: To evaluate early-stage prostate cancer (PCa) radiotherapy treatment patterns and outcomes among Ghanaian men (GM) compared with US men (USM). MATERIALS AND METHODS: This retrospective study consists of 987 National Comprehensive Cancer Network low risk, favorable intermediate risk, and unfavorable intermediate risk PCa patient subgroups; GM (173) and USM (814). Differences in baseline covariates and clinical characteristics between GM and USM were analyzed using χ and Mann-Whitney test while Cox Proportional Hazards model was used to assess freedom from biochemical failure differences between the study groups. RESULTS: Median follow-up for this study was 40 months. GM were diagnosed at a younger median age (64 vs. 68 y, P<0.001) with heavier unfavorable intermediate risk disease burden (32.4% vs. 19.2%) compared with USM. Significant differences were identified in median external beam radiotherapy dose (72.4 vs. 78 Gy, P<0.001); brachytherapy utilization (49.7% vs. 80.6%, P<0.001) and androgen deprivation therapy for intermediate risk disease (48.4% vs. 21.0%, P<0.001) between GM and USM, respectively. GM with low risk and favorable intermediate risk PCa were at increased risk of biochemical recurrence compared with USM with adjusted hazard ratio: 5.15 (1.27 to 20.7), P=0.02 and 4.64 (1.20 to 17.92), P=0.02, respectively. CONCLUSIONS: Compared with USM, GM with low and favorable intermediate risk PCa may experience less durable disease control following standard treatment recommendations. Results suggest differences in radiation treatment and possible inherent differences between the 2 populations. This data will aid in developing research strategies to improve treatment outcomes in GM.


Assuntos
Braquiterapia/métodos , Causas de Morte , Neoplasias da Próstata/patologia , Neoplasias da Próstata/radioterapia , Fatores Etários , Idoso , Antagonistas de Androgênios/uso terapêutico , Braquiterapia/mortalidade , Estudos de Coortes , Intervalo Livre de Doença , Gana , Hospitais de Ensino , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Neoplasias da Próstata/mortalidade , Dosagem Radioterapêutica , Estudos Retrospectivos , Medição de Risco , Estatísticas não Paramétricas , Análise de Sobrevida , Resultado do Tratamento , Estados Unidos
17.
Ghana Med J ; 52(1): 61-65, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30013261

RESUMO

Castleman disease is a rare cause of lymphoid hyperplasia and may result in localized symptoms or an aggressive, multisystem disorder. It can mimic other diseases like lymphoma or tuberculosis. It classically presents as a mediastinal mass that involves the lymphatic tissue primarily but can also affect extra lymphatic sites including the lungs, larynx, parotid glands, pancreas, meninges, and muscles. In HIV and HHV8-negative patients with idiopathic multi-centric Castleman disease, pathogenesis may involve autoimmune mechanisms. We highlight and report a case of a 34-year-old Ghanaian female who was successfully diagnosed and managed for Sjögren's as well as plasma cell variant Castleman disease with combination chemotherapy and rituximab followed by eighteen months maintenance therapy with pulse chlorambucil and prednisolone and three monthly rituximab.


Assuntos
Hiperplasia do Linfonodo Gigante/tratamento farmacológico , Plasmócitos/patologia , Síndrome de Sjogren/tratamento farmacológico , Adulto , Anemia Hemolítica/etiologia , Hiperplasia do Linfonodo Gigante/complicações , Clorambucila/administração & dosagem , Diagnóstico Diferencial , Quimioterapia Combinada , Feminino , Gana , Humanos , Prednisolona/administração & dosagem , Rituximab/administração & dosagem , Síndrome de Sjogren/complicações
18.
J Glob Oncol ; 4: 1-13, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-30085846

RESUMO

Purpose Data on prostate cancer (PCa) treatment in Africa remains under-reported. We present a review of the management of PCa at the cancer center of the largest tertiary referral facility in Ghana, with emphasis on curative treatment. Methods We retrospectively reviewed data on 1,074 patients seen at the National Center for Radiotherapy and Nuclear Medicine from 2003 to 2016. Patient and disease characteristics at presentation are presented using descriptive statistics. The χ2 and Fisher's exact tests and Mann-Whitney U test were used to analyze differences between categorical and continuous variables, respectively. Methods of survival analysis were used to evaluate the relative risk of biochemical disease-free survival (bDFS). Results Seventy percent of the study population presented with localized disease. High-risk disease presentation accounted for 64.4% of these patients. Only 57.6% of patients with localized disease received curative radiotherapy. The 5-year overall survival for the curative cohort was 96% (interquartile range, 93% to 98%). The 5-year bDFS rates for low-, intermediate-, and high-risk groups were 95%, 70%, and 48%, respectively. Both Gleason score and pretreatment prostate-specific antigen were significant predictors for bDFS in multivariable analysis. Conclusion We show that the majority of patients with PCa have locally advanced disease at the time of presentation for radiotherapy. bDFS was significantly better for low- and intermediate-risk than for high-risk disease. These data emphasize the dire need to re-evaluate screening and patient education of PCa in regions of the world with high incidence and mortality as well as the need for improved access to care and treatment delivery.


Assuntos
Neoplasias da Próstata/radioterapia , Idoso , Gana , Humanos , Masculino , Neoplasias da Próstata/patologia
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