Publications by authors named "Yao Tettey"

34 Publications

Overall and abdominal obesity and prostate cancer risk in a West African population: An analysis of the Ghana Prostate Study.

Int J Cancer 2020 11 6;147(10):2669-2676. Epub 2020 May 6.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA.

Obesity has been associated with an increased risk of advanced prostate cancer. However, most studies have been conducted among North American and European populations. Prostate cancer mortality appears elevated in West Africa, yet risk factors for prostate cancer in this region are unknown. We thus examined the relationship between obesity and prostate cancer using a case-control study conducted in Accra, Ghana in 2004 to 2012. Cases and controls were drawn from a population-based sample of 1037 men screened for prostate cancer, yielding 73 cases and 964 controls. An additional 493 incident cases were recruited from the Korle-Bu Teaching Hospital. Anthropometric measurements were taken at enrollment. We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between body mass index (BMI), waist circumference (WC), waist-hip ratio (WHR) and prostate cancer, adjusting for potential confounders. The mean BMI was 25.1 kg/m for cases and 24.3 kg/m for controls. After adjustment, men with BMI ≥ 30 kg/m had an increased risk of prostate cancer relative to men with BMI < 25 kg/m (OR 1.86, 95% CI 1.11-3.13). Elevated WC (OR 1.76, 95% CI 1.24-2.51) and WHR (OR 1.46, 95% CI 0.99-2.16) were also associated with prostate cancer. Associations were not modified by smoking status and were evident for low- and high-grade disease. These findings indicate that overall and abdominal obesity are positively associated with prostate cancer among men in Ghana, implicating obesity as a potentially modifiable risk factor for prostate cancer in this region.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ijc.33026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7530105PMC
November 2020

Establishing a Cancer Registry in a Resource-Constrained Region: Process Experience From Ghana.

JCO Glob Oncol 2020 04;6:610-616

Department of Pediatrics, Center of Policy, Outcomes, and Prevention, Stanford University School of Medicine, Stanford, CA.

Purpose: In a review of cancer incidence across continents (GLOBOCAN 2012), data sources from Ghana were classified as Frequencies, the lowest classification for inclusion, signifying the worst data quality for inclusion in the analysis. Recognizing this deficiency, the establishment of a population-based cancer registry was proposed as part of a broader cancer control plan.

Methods: The registry was examined under the following headings: policy, data source, and administrative structure; external support and training; and definition of geographic coverage.

Results: The registry was set up based on the Ghana policy document on the strategy for cancer control. The paradigm shift ensured subscription to one data collection software (CanReg 5) in the country. The current approach consists of trained registrars based in the registry who conduct active data abstraction at the departments and units of the hospital and pathologic services. To ensure good governance, an administrative structure was created, including an advisory board, a technical committee, and registry staff. External support for the establishment of the Accra Cancer Registry has come mainly from Stanford University and the African Cancer Registry Network, in collaboration with the University of Ghana. Unlike previous attempts, this registry has a well-defined population made up of nine municipal districts.

Conclusion: The Accra Cancer Registry was established as a result of the lessons learned from failed previous attempts and aim to provide a model for setting up other cancer registries in Ghana. It will eventually be the focal point where all the national data can be collated.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1200/JGO.19.00387DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7193799PMC
April 2020

Genetic signatures of gene flow and malaria-driven natural selection in sub-Saharan populations of the "endemic Burkitt Lymphoma belt".

PLoS Genet 2019 03 8;15(3):e1008027. Epub 2019 Mar 8.

Stanford Cancer Institute, Stanford University, Stanford, California, United States of America.

Populations in sub-Saharan Africa have historically been exposed to intense selection from chronic infection with falciparum malaria. Interestingly, populations with the highest malaria intensity can be identified by the increased occurrence of endemic Burkitt Lymphoma (eBL), a pediatric cancer that affects populations with intense malaria exposure, in the so called "eBL belt" in sub-Saharan Africa. However, the effects of intense malaria exposure and sub-Saharan populations' genetic histories remain poorly explored. To determine if historical migrations and intense malaria exposure have shaped the genetic composition of the eBL belt populations, we genotyped ~4.3 million SNPs in 1,708 individuals from Ghana and Northern Uganda, located on opposite sides of eBL belt and with ≥ 7 months/year of intense malaria exposure and published evidence of high incidence of BL. Among 35 Ghanaian tribes, we showed a predominantly West-Central African ancestry and genomic footprints of gene flow from Gambian and East African populations. In Uganda, the North West population showed a predominantly Nilotic ancestry, and the North Central population was a mixture of Nilotic and Southern Bantu ancestry, while the Southwest Ugandan population showed a predominant Southern Bantu ancestry. Our results support the hypothesis of diverse ancestral origins of the Ugandan, Kenyan and Tanzanian Great Lakes African populations, reflecting a confluence of Nilotic, Cushitic and Bantu migrations in the last 3000 years. Natural selection analyses suggest, for the first time, a strong positive selection signal in the ATP2B4 gene (rs10900588) in Northern Ugandan populations. These findings provide important baseline genomic data to facilitate disease association studies, including of eBL, in eBL belt populations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.pgen.1008027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6426263PMC
March 2019

Usual adult occupation and risk of prostate cancer in West African men: the Ghana Prostate Study.

Occup Environ Med 2019 02 7;76(2):71-77. Epub 2018 Dec 7.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA.

Objectives: Established prostate cancer (PCa) risk factors include age, family history of PCa and African ancestry. Studies, mostly among highly screened, predominantly European ancestral populations, suggest that employment in certain occupations (eg, farming, military) may also have an increased risk for PCa. Here, we evaluated the association between usual adult occupation and PCa risk in Ghanaian men, a population with historically low rates of PCa screening.

Methods: The Ghana Prostate Study is a case-control study of PCa that was conducted from 2004 to 2012 in 749 cases and 964 controls. In-person interviews were conducted to collect information from participants, including longest held job. Industrial hygienists classified job titles into occupational categories. Unconditional logistic regression was used to calculate ORs and 95% CIs for the association between longest held job and PCa risk (overall, aggressive (Gleason≥7)), controlling for potential confounders.

Results: Risk was increased among men in management (overall PCa OR=2.2, 95% CI 1.4 to 3.2; aggressive PCa OR=2.2, 95% CI 1.3 to 3.5) and military occupations (overall PCa OR=3.4, 95% CI 1.7 to 7.0; aggressive PCa OR=3.5, 95% CI 1.5 to 8.3). Risks were also elevated for management and military-specific jobs based on 3-digit level Standard Occupational Classification definitions. Sensitivity analyses accounting for access to medical care did not show significant differences.

Conclusions: Our study provides some evidence for increased risk of PCa among men in management and military occupations, which is consistent with the published literature. Additional research is needed to clarify the drivers of the associations between these occupations and PCa.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/oemed-2018-105391DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6335162PMC
February 2019

Development, Evaluation, and Implementation of a Pan-African Cancer Research Network: Men of African Descent and Carcinoma of the Prostate.

J Glob Oncol 2018 09;4:1-14

Caroline Andrews, Brian Fortier, Amy Hayward, Ruth Lederman, and Timothy R. Rebbeck; Dana-Farber Cancer Institute; Alex Orfanos and Yuri Quintana, Beth Israel Deaconess Medical Center; Timothy R. Rebbeck, Harvard T.H. Chan School of Public Health, Boston, MA; Lindsay Petersen, Jo McBride, Desiree C. Petersen, Olabode Ajayi, Paidamoyo Kachambwa, Moleboheng Seutloali, Aubrey Shoko, Mamokhosana Mokhosi, and Reinhard Hiller, Centre for Proteomic and Genomic Research; Pedro Fernandez and Hayley Irusen, Stellenbosch University and Tygerberg Hospital, Cape Town; Wenlong C. Chen and Elvira Singh, National Cancer Registry, National Health Laboratory Service; Wenlong C. Chen, Elvira Singh, Maureen Joffe, Audrey Pentz, and Cassandra Claire Soo, University of Witwatersrand, Johannesburg, South Africa; Marcia Adams, Chrissie Ongaco, Elizabeth Pugh, Jane Romm, and Tameka Shelford, Center for Inherited Disease Research, Baltimore; Michael B. Cook, National Cancer Institute, National Institutes of Health, Bethesda, MD; Frank Chinegwundoh, Bart's Health National Health Services Trust, London, United Kingdom; Ben Adusei, Sunny Mante, and Nana Yaa Snyper, 37 Military Hospital; Andrew A. Adjei, Richard Biritwum, Richard Gyasi, Mathew Kyei, James E. Mensah, Julian Okine, Vicky Okyne, Isabella Rockson, Evelyn Tay, Yao Tettey, and Edward Yeboah, Korle-Bu Teaching Hospital, Accra, Ghana; Ilir Agalliu, David W. Lounsbury, and Thomas Rohan, Albert Einstein College of Medicine, Bronx; Judith S. Jacobson, Alfred I. Neugut, and Edward Gelmann, Columbia University, New York, NY; Joseph Lachance, Georgia Institute of Technology, Atlanta, GA; Cristine N. Duffy and Ann Hsing, Stanford University, Stanford Cancer Institute, Stanford, CA; Cherif Dial, Thierno Amadou Diallo, Mohamed Jalloh, Serigne Magueye Gueye, and Papa Moussa Sène Kane, Hôpital Général de Grand Yoff, Institute de Formation et de la Recherche en Urologie et de la Santé de la Famillie; Halimatou Diop, Anna Julienne Ndiaye, Amina Sow Sall, and Ndeye Coumba Toure-Kane, Hôpital Aristide Le Dantec, Dakar, Senegal; Ezenwa Onyemata and Alash'le Abimiku, Institute of Human Virology, H3 African Biorepository Initiative; Oseremen Aisuodionoe-Shadrach, Abubakar Mustapha Jamda, Peter Oluwole Olabode, Maxwell Madueke Nwegbu, and Olalekan Hafees Ajibola, University of Abuja; Oseremen Aisuodionoe-Shadrach, Abubakar Mustapha Jamda, Peter Oluwole Olabode, and Maxwell Madueke Nwegbu, University of Abuja Teaching Hospital, Abuja; Olushola Jeremiah Ajamu and Yakubu Garba Ambuwa, Federal Medical Center, Keffi; Akindele Olupelumi Adebiyi, Michael Asuzu, Olufemi Ogunbiyi, Olufemi Popoola, Olayiwola Shittu, Olukemi Amodu, Emeka Odiaka, and Ifeoluwa Makinde, University College Hospital, Ibadan, Nigeria.

Purpose: Cancer of the prostate (CaP) is the leading cancer among men in sub-Saharan Africa (SSA). A substantial proportion of these men with CaP are diagnosed at late (usually incurable) stages, yet little is known about the etiology of CaP in SSA.

Methods: We established the Men of African Descent and Carcinoma of the Prostate Network, which includes seven SSA centers partnering with five US centers to study the genetics and epidemiology of CaP in SSA. We developed common data elements and instruments, regulatory infrastructure, and biosample collection, processing, and shipping protocols. We tested this infrastructure by collecting epidemiologic, medical record, and genomic data from a total of 311 patients with CaP and 218 matched controls recruited at the seven SSA centers. We extracted genomic DNA from whole blood, buffy coat, or buccal swabs from 265 participants and shipped it to the Center for Inherited Disease Research (Baltimore, MD) and the Centre for Proteomics and Genomics Research (Cape Town, South Africa), where genotypes were generated using the UK Biobank Axiom Array.

Results: We used common instruments for data collection and entered data into the shared database. Double-entered data from pilot participants showed a 95% to 98% concordance rate, suggesting that data can be collected, entered, and stored with a high degree of accuracy. Genotypes were obtained from 95% of tested DNA samples (100% from blood-derived DNA samples) with high concordance across laboratories.

Conclusion: We provide approaches that can produce high-quality epidemiologic and genomic data in multicenter studies of cancer in SSA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1200/JGO.18.00063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6223491PMC
September 2018

Two Novel Susceptibility Loci for Prostate Cancer in Men of African Ancestry.

J Natl Cancer Inst 2017 08;109(8)

Department of Cancer Epidemiology, Moffitt Cancer Center and Research Institute, Tampa, FL.

Prostate cancer incidence is 1.6-fold higher in African Americans than in other populations. The risk factors that drive this disparity are unknown and potentially consist of social, environmental, and genetic influences. To investigate the genetic basis of prostate cancer in men of African ancestry, we performed a genome-wide association meta-analysis using two-sided statistical tests in 10 202 case subjects and 10 810 control subjects. We identified novel signals on chromosomes 13q34 and 22q12, with the risk-associated alleles found only in men of African ancestry (13q34: rs75823044, risk allele frequency = 2.2%, odds ratio [OR] = 1.55, 95% confidence interval [CI] = 1.37 to 1.76, P = 6.10 × 10-12; 22q12.1: rs78554043, risk allele frequency = 1.5%, OR = 1.62, 95% CI = 1.39 to 1.89, P = 7.50 × 10-10). At 13q34, the signal is located 5' of the gene IRS2 and 3' of a long noncoding RNA, while at 22q12 the candidate functional allele is a missense variant in the CHEK2 gene. These findings provide further support for the role of ancestry-specific germline variation in contributing to population differences in prostate cancer risk.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jnci/djx084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5448553PMC
August 2017

Unrecognized human immunodeficiency virus infection and risk factors among elderly medical patients at the Korle Bu teaching hospital, Accra, Ghana.

Trop Dis Travel Med Vaccines 2016 2;2:18. Epub 2016 Sep 2.

Department of Pathology, School of Biomedical and Allied Health Sciences, College of Health Sciences, University of Ghana, Accra, Ghana.

Background: The human immunodeficiency virus (HIV) infection usually infects persons in the reproductive age group (15-49 years), but elderly people are also susceptible. Many people in sub-Saharan Africa including Ghana believe that elderly people are not at risk for HIV. Despite numerous reports of the high prevalence of HIV infection among the elderly worldwide, there are no from Ghana. This work determined the sero-prevalence of HIV infection and risk factors for its transmission among 1,100 hospitalized elderly people at the Korle Bu Teaching Hospital (KBTH), Accra, Ghana.

Methods: Subjects voluntarily completed a risk-factor questionnaire and provided a blood specimen for HIV testing.

Results: Of the study participants, 440 were male (mean age: 64 ± 10.55 years), and 660 were female (mean age: 63 ± 9.51 years). The overall HIV-1 sero-prevalence among the subjects was 4.18 % ( = 46). On multivariate analysis, there was no statistical significance between the socio-demographics or risk factors and the HIV status of the participants.

Conclusion: The results suggest high prevalence of HIV-1 among hospitalized elderly people at KBTH, recommending the need to include the elderly in HIV/AIDS testing, prevention, and control programmes.

Trial Registration: Trial registration number: MS-Et/M.9 - p4.10/2012-2013. Registered: 10th April, 2013.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40794-016-0034-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5530923PMC
September 2016

TMPRSS2:ERG Gene Fusions in Prostate Cancer of West African Men and a Meta-Analysis of Racial Differences.

Am J Epidemiol 2017 Dec;186(12):1352-1361

Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.

The prevalence of fusions of the transmembrane protease, serine 2, gene (TMPRSS2) with the erythroblast transformation-specific-related gene (ERG), or TMPRSS2:ERG, in prostate cancer varies by race. However, such somatic aberration and its association with prognostic factors have neither been studied in a West African population nor been systematically reviewed in the context of racial differences. We used immunohistochemistry to assess oncoprotein encoded by the ERG gene as the established surrogate of ERG fusion genes among 262 prostate cancer biopsies from the Ghana Prostate Study (2004-2006). Poisson regression with robust variance estimation provided prevalence ratios and 95% confidence intervals of ERG expression in relation to patient characteristics. We found that 47 of 262 (18%) prostate cancers were ERG-positive, and being negative for ERG staining was associated with higher Gleason score. We further conducted a systematic review and meta-analysis of TMPRSS2:ERG fusions in relation to race, Gleason score, and tumor stage, combining results from Ghana with 40 additional studies. Meta-analysis showed the prevalence of TMPRSS2:ERG fusions in prostate cancer to be highest in men of European descent (49%), followed by men of Asian (27%) and then African (25%) descent. The lower prevalence of TMPRSS2:ERG fusions in men of African descent implies that alternative genomic mechanisms might explain the disproportionately high prostate cancer burden in such populations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/aje/kwx235DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5860576PMC
December 2017

Use of skin-lightening products among selected urban communities in Accra, Ghana.

Int J Dermatol 2017 Jan;56(1):32-39

Department of Pathology, University of Ghana School of Biomedical and Allied Health Sciences, Accra, Ghana.

Background: The practice of skin lightening has been reported from North America, Europe, Asia, and Africa. In literature, some prevalence rates exceed 50%, and both sexes are involved. Common agents used include hydroquinone, mercury, corticosteroids, and caustic agents. The agents are easily accessible and affordable with very little regulation. Cutaneous and systemic side effects occur but do not appear to be a deterrent, as the notion of light skin as a surrogate for beauty is strong. In Ghana, anecdotal reports of high bleaching rates among certain urban communities resulted in a study supported by the Food and Drugs Authority to determine various facets of this practice.

Methods: A cross-sectional study among adults in selected urban fishing communities of Accra was undertaken. Consecutive cases were enrolled after written informed consent. A questionnaire was administered, followed by physical examination and clinical photographs. Descriptive statistics were used to analyze the data.

Results: Of the 555 participants from the three communities, prevalence was 279 (50.3%). Duration of use ranged from 2 months to 17 years. Approximately 212 (76%) used more than one product, and 231 (82%) used agents on their face and body. Dermatological features were hypopigmentation 270 (96.8%), other color changes including ochronosis 241 (86.4%), changes in consistency 141 (50.3%), striae 157 (56.3%), and infections 42 (15.1%).

Conclusions: The prevalence of skin bleaching was 50.3% in these communities, which is high considering the adverse effects from the practice. We recommend regulation of products by enforcing the law, more education, and a population prevalence study.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ijd.13449DOI Listing
January 2017

Atlas of prostate cancer heritability in European and African-American men pinpoints tissue-specific regulation.

Nat Commun 2016 Apr 7;7:10979. Epub 2016 Apr 7.

Department of Public Health Sciences, Henry Ford Hospital, Detroit, Michigan 48202, USA.

Although genome-wide association studies have identified over 100 risk loci that explain ∼33% of familial risk for prostate cancer (PrCa), their functional effects on risk remain largely unknown. Here we use genotype data from 59,089 men of European and African American ancestries combined with cell-type-specific epigenetic data to build a genomic atlas of single-nucleotide polymorphism (SNP) heritability in PrCa. We find significant differences in heritability between variants in prostate-relevant epigenetic marks defined in normal versus tumour tissue as well as between tissue and cell lines. The majority of SNP heritability lies in regions marked by H3k27 acetylation in prostate adenoc7arcinoma cell line (LNCaP) or by DNaseI hypersensitive sites in cancer cell lines. We find a high degree of similarity between European and African American ancestries suggesting a similar genetic architecture from common variation underlying PrCa risk. Our findings showcase the power of integrating functional annotation with genetic data to understand the genetic basis of PrCa.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/ncomms10979DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4829663PMC
April 2016

Prostate Cancer Susceptibility in Men of African Ancestry at 8q24.

J Natl Cancer Inst 2016 Jul 27;108(7). Epub 2016 Jan 27.

Affiliations of authors: Department of Preventive Medicine (YH, KAR, DJH, SAI, FRS, GC, LCP, XS, GAC, DOS, DVC, BEH, CAH) and Department of Urology (GAC), Keck School of Medicine, and Norris Comprehensive Cancer Center (SAI, FRS, GC, GAC, DOS, DVC, BEH, CAH), University of Southern California , Los Angeles, CA ; University of Arizona College of Medicine and University of Arizona Cancer Center , Tucson, AZ (RAK); Department of Epidemiology (SSS) and Department of Urology (CAP), University of Texas M. D. Anderson Cancer Center , Houston, TX ; Department of Public Health Sciences (BAR) and Department of Public Health Sciences (CND), Henry Ford Hospital , Detroit, MI ; Department of Preventive Medicine, Stony Brook University , Stony Brook, NY (BN, MCL, SYW, AJMH); James Buchanan Brady Urological Institute, Johns Hopkins Hospital and Medical Institution , Baltimore, MD (WBI); Division of Public Health Sciences (JLS, SK) and SWOG Statistical Center (PJG), Fred Hutchinson Cancer Research Center , Seattle, WA ; Department of Epidemiology, School of Public Health, University of Washington , Seattle, WA (JLS); Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine , Nashville, TN (WZ, WJB); Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health , Bethesda, MD (SIB, ZW, MBC, SJC); Cancer Genomics Research Laboratory, NCI-DCEG, SAIC-Frederick Inc. , Frederick, MD (ZW); Program for Personalized Cancer Care and Department of Surgery, NorthShore University HealthSystem , Evanston, IL (JX); Department of Genetics (NR, DR, AT, AA, DQ, SM) and Howard Hughes Medical Institute (DR, SM), Harvard Medical School, Harvard University , Boston, MA ; Broad Institute of MIT and Harvard , Cambridge, MA (NR, DR, AT, AA, DQ, SM); Department of Pathology and Laboratory Medicine and Department of Human Genetics, David Geffen School of Medicine, University of California , Los Angeles, Los Angeles, CA (BP); Howard Hughes Medical Institute, Department of Medicine, School of Medicine, University of California , San Diego, San Diego, CA (DN, MGR, RSJ); Epidemiology Research Program, American Cancer Society , Atlanta, GA (SMG, VLS); Korle Bu Teaching Hospital , Accra , Ghana (EDY, YT, RBB, AAA, ET); University of Ghana Medical School , Accra , Ghana (EDY, YT, RBB, AAA, ET); Westat , Rockville, MD (AT, SN); School of Public Health, University of California , Berkeley, Berkeley, CA (APC); Cancer Prevention Institute of California , Fremont, CA (EMJ, AWH, LC); Stanford University School of Medicine and Stanford Cancer Institute , Palo Alto, CA (EMJ, AWH, LC); Department of Urology, Northwestern University , Chicago, IL (ABM); Department of Epidemiology, Harvard School of Public Health , Boston, MA (LBS, WJB); The Translational Genomics Research Institute , Phoenix, AZ (JC); Chronic Disease Research Centre and Faculty of Medical Sciences, University of the West Indies , Bridgetown, Barbados (AJMH); Glickman Urological & Kidney Institute, Cleveland Clinic , Cleveland, OH (EAK); Center for Cancer Genomics, Wake Forest School of Medicine , Winston-Salem, NC (SLZ); Department of Epidemiology and Biostatistics and Institute for Human Genetics, University of California , San Francisco, San Francisco, CA (JSW); School of Public Health, Makerere University College of Health Sciences , Kampala, Uganda (AL, SW); Uro Care , Kampala , Uganda (SW).

The 8q24 region harbors multiple risk variants for distinct cancers, including >8 for prostate cancer. In this study, we conducted fine mapping of the 8q24 risk region (127.8-128.8Mb) in search of novel associations with common and rare variation in 4853 prostate cancer case patients and 4678 control subjects of African ancestry. All statistical tests were two-sided. We identified three independent associations at P values of less than 5.00×10(-8), all of which were replicated in studies from Ghana and Uganda (combined sample = 5869 case patients, 5615 control subjects; rs114798100: risk allele frequency [RAF] = 0.04, per-allele odds ratio [OR] = 2.31, 95% confidence interval [CI] = 2.04 to 2.61, P = 2.38×10(-40); rs72725879: RAF = 0.33, OR = 1.37, 95% CI = 1.30 to 1.45, P = 3.04×10(-27); and rs111906932: RAF = 0.03, OR = 1.79, 95% CI = 1.53 to 2.08, P = 1.39×10(-13)). Risk variants rs114798100 and rs111906923 are only found in men of African ancestry, with rs111906923 representing a novel association signal. The three variants are located within or near a number of prostate cancer-associated long noncoding RNAs (lncRNAs), including PRNCR1, PCAT1, and PCAT2. These findings highlight ancestry-specific risk variation and implicate prostate-specific lncRNAs at the 8q24 prostate cancer susceptibility region.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jnci/djv431DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4948565PMC
July 2016

Triple-Negative Breast Cancer in Ghanaian Women: The Korle Bu Teaching Hospital Experience.

Breast J 2015 Nov-Dec;21(6):627-33

University of Michigan Medical School, Ann Arbor, Michigan.

Breast cancers that have negative or extremely low expression of estrogen receptor and progesterone receptor and non-amplification of human epidermal growth factor receptor-2 (HER2)/neu are termed triple-negative breast cancer (TNBC). The majority of TNBC tumors belong to the biologically aggressive basal subtype, and they cannot be managed with targeted endocrine or anti-HER2/neu agents. In western, high resource environments, risk factors for TNBC include younger age at diagnosis and hereditary susceptibility. Women of African ancestry in the United States and in continental Africa have higher frequencies of TNBC, prompting speculation that this risk may have an inherited basis and may at least partially explain breast cancer survival disparities related to racial/ethnic identity. Efforts to document and confirm the breast cancer burden of continental Africa have been hampered by the limited availability of registry and immunohistochemistry resources. Our goal was to evaluate the breast cancers diagnosed in one of the largest health care facilities in western Africa, and to compare the frequencies as well as risk factors for TNBC versus non-TNBC in this large referral tertiary hospital. The Korle Bu Teaching Hospital is affiliated with the University of Ghana and is located in Accra, the capital of Ghana. We conducted an institutional, Department of Pathology-based review of the breast cancer cases seen at this facility for the 2010 calendar year, and for which histopathologic specimens were available. The overall study population of 223 breast cancer cases had a median age of 52.4 years, and most had palpable tumors larger than 5 cm in diameter. More than half were TNBC (130; 58.3%). We observed similar age-specific frequencies, distribution of stage at diagnosis and tumor grade among cases of TNBC compared to cases of non-TNBC. Ghanaian breast cancer patients tend to have an advanced stage distribution and relatively younger age at diagnosis compared to Caucasian Americans and African Americans. The triple-negative molecular marker pattern was the most common subtype of breast cancer seen among this sample of Ghanaian women, regardless of age, tumor grade, or stage of diagnosis. Research into the molecular pathogenesis of TNBC may help elucidate the reasons for its increased prevalence among women with African ancestry.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/tbj.12527DOI Listing
August 2016

Integration of multiethnic fine-mapping and genomic annotation to prioritize candidate functional SNPs at prostate cancer susceptibility regions.

Hum Mol Genet 2015 Oct 10;24(19):5603-18. Epub 2015 Jul 10.

Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.

Interpretation of biological mechanisms underlying genetic risk associations for prostate cancer is complicated by the relatively large number of risk variants (n = 100) and the thousands of surrogate SNPs in linkage disequilibrium. Here, we combined three distinct approaches: multiethnic fine-mapping, putative functional annotation (based upon epigenetic data and genome-encoded features), and expression quantitative trait loci (eQTL) analyses, in an attempt to reduce this complexity. We examined 67 risk regions using genotyping and imputation-based fine-mapping in populations of European (cases/controls: 8600/6946), African (cases/controls: 5327/5136), Japanese (cases/controls: 2563/4391) and Latino (cases/controls: 1034/1046) ancestry. Markers at 55 regions passed a region-specific significance threshold (P-value cutoff range: 3.9 × 10(-4)-5.6 × 10(-3)) and in 30 regions we identified markers that were more significantly associated with risk than the previously reported variants in the multiethnic sample. Novel secondary signals (P < 5.0 × 10(-6)) were also detected in two regions (rs13062436/3q21 and rs17181170/3p12). Among 666 variants in the 55 regions with P-values within one order of magnitude of the most-associated marker, 193 variants (29%) in 48 regions overlapped with epigenetic or other putative functional marks. In 11 of the 55 regions, cis-eQTLs were detected with nearby genes. For 12 of the 55 regions (22%), the most significant region-specific, prostate-cancer associated variant represented the strongest candidate functional variant based on our annotations; the number of regions increased to 20 (36%) and 27 (49%) when examining the 2 and 3 most significantly associated variants in each region, respectively. These results have prioritized subsets of candidate variants for downstream functional evaluation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/hmg/ddv269DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4572069PMC
October 2015

Through the lens of the clinician: autopsy services and utilization in a large teaching hospital in Ghana.

BMC Res Notes 2014 Dec 23;7:943. Epub 2014 Dec 23.

Department of Community Health, School of Public Health, College of Health Sciences, University of Ghana, Room 46, P, O, Box 4236, Korle-Bu, Accra, Ghana.

Background: Declining hospital autopsy rates in many countries have generated considerable concern. The survey determined challenges of the autopsy service in a large Teaching Hospital in Ghana, from the perspective of clinicians.

Methods: This was a cross-sectional study of doctors at the Korle-Bu Teaching Hospital (KBTH) over in 2012. The data was collected using a 69 item self-administered structured questionnaire. In all a total of 215 questionnaires were sent out and 119 doctors responded. Data was collected on the challenges of the autopsy services and barriers to autopsy request from the perspectives of clinicians. Survey data were analyzed by simple descriptive statistics (i.e. proportions, ratios and percentages. Data from survey was analyzed with SPSS version 21.

Results: The most common reasons for requesting autopsies were to answer clinical questions, 55 (46.2%) and in cases of uncertain diagnosis, 54 (45.4%). Main demand side barriers to the use of autopsy services by clinicians were reluctance of family to give consent for autopsy 100 (84%), due to cultural and religious objections 89 (74.8%), extra funeral cost to family53 (44.5%) and increased duration of stay of body in the morgue 19 (16%). Health system barriers included delayed feedback from autopsy service 54 (45.4%), difficulties following up the autopsy process 40 (33.6%) due to uncertainties in the timing of particular events in the autopsy process, and long waiting time for autopsy reports 81 (68.1%). More than a third of clinicians 43 (36.2%), received full autopsy report beyond three weeks and 75 (63.1%) clinicians had concerns with the validity of reports issued by the autopsy service (i.e. reports lack specificity or at variance with clinical diagnosis, no toxicological, histological or tissue diagnoses are performed).

Conclusion: The autopsy service should restructure itself efficiently and management should support the provision of histological and toxicological services. Strengthening internal and external quality improvement and control of autopsies in the Hospital are essential.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/1756-0500-7-943DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4307638PMC
December 2014

A meta-analysis of 87,040 individuals identifies 23 new susceptibility loci for prostate cancer.

Nat Genet 2014 Oct 14;46(10):1103-9. Epub 2014 Sep 14.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, US National Institute of Health, Bethesda, Maryland, USA.

Genome-wide association studies (GWAS) have identified 76 variants associated with prostate cancer risk predominantly in populations of European ancestry. To identify additional susceptibility loci for this common cancer, we conducted a meta-analysis of > 10 million SNPs in 43,303 prostate cancer cases and 43,737 controls from studies in populations of European, African, Japanese and Latino ancestry. Twenty-three new susceptibility loci were identified at association P < 5 × 10(-8); 15 variants were identified among men of European ancestry, 7 were identified in multi-ancestry analyses and 1 was associated with early-onset prostate cancer. These 23 variants, in combination with known prostate cancer risk variants, explain 33% of the familial risk for this disease in European-ancestry populations. These findings provide new regions for investigation into the pathogenesis of prostate cancer and demonstrate the usefulness of combining ancestrally diverse populations to discover risk loci for disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/ng.3094DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4383163PMC
October 2014

Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33.

Hum Mol Genet 2014 Dec 15;23(24):6616-33. Epub 2014 Jul 15.

Department of Preventive Medicine, Biostatistics Division, Keck School of Medicine and.

Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/hmg/ddu363DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4240198PMC
December 2014

A comprehensive resequence-analysis of 250 kb region of 8q24.21 in men of African ancestry.

Prostate 2014 May;74(6):579-89

Background: Genome-wide association studies (GWAS) have identified that a ∼1 M region centromeric to the MYC oncogene on chromosome 8q24.21 harbors at least five independent loci associated with prostate cancer risk and additional loci associated with cancers of breast, colon, bladder, and chronic lymphocytic leukemia (CLL). Because GWAS identify genetic markers that may be indirectly associated with disease, fine-mapping based on sequence analysis provides important insights into patterns of linkage disequilibrium (LD) and is critical in defining the optimal variants to nominate for biological follow-up.

Methods: To catalog variation in individuals of African ancestry, we resequenced a region (250 kb; chr8:128,050, 768–128, 300,801, hg19) containing several prostate cancer susceptibility loci as well as a locus associated with CLL. Our samples included 78 individuals from Ghana and 47 of African-Americans from Johns Hopkins University.

Results: After quality control metrics were applied to next-generation sequence data, 1,838 SNPs were identified. Of these, 285 were novel and not yet reported in any public database. Using genotypes derived from sequencing, we refined the LD and recombination hotspots within the region and determined a set of tag SNPs to be used in future fine-mapping studies. Based on LD, we annotated putative risk loci and their surrogates using ENCODE data, which should help guide laboratory studies.

Conclusions: In comparison to the 1000 Genome Project data, we have identified additional variants that could be important in establishing priorities for future functional work designed to explain the biological basis of associations between SNPs and both prostate cancer and CLL.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/pros.22726DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4199861PMC
May 2014

High prevalence of screen detected prostate cancer in West Africans: implications for racial disparity of prostate cancer.

J Urol 2014 Sep 18;192(3):730-5. Epub 2014 Apr 18.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.

Purpose: To our knowledge the reasons for the high rates of prostate cancer in black American men are unknown. Genetic and lifestyle factors have been implicated. Better understanding of prostate cancer rates in West African men would help clarify why black American men have such high rates since the groups share genetic ancestry and yet have different lifestyles and screening practices. To estimate the prostate cancer burden in West African men we performed a population based screening study with biopsy confirmation in Ghana.

Materials And Methods: We randomly selected 1,037 healthy men 50 to 74 years old from Accra, Ghana for prostate cancer screening with prostate specific antigen testing and digital rectal examination. Men with a positive screen result (positive digital rectal examination or prostate specific antigen greater than 2.5 ng/ml) underwent transrectal ultrasound guided biopsies.

Results: Of the 1,037 men 154 (14.9%) had a positive digital rectal examination and 272 (26.2%) had prostate specific antigen greater than 2.5 ng/ml, including 166 with prostate specific antigen greater than 4.0 ng/ml. A total of 352 men (33.9%) had a positive screen by prostate specific antigen or digital rectal examination and 307 (87%) underwent biopsy. Of these men 73 were confirmed to have prostate cancer, yielding a 7.0% screen detected prostate cancer prevalence (65 patients), including 5.8% with prostate specific antigen greater than 4.0 ng/ml.

Conclusions: In this relatively unscreened population in Africa the screen detected prostate cancer prevalence is high, suggesting a possible role of genetics in prostate cancer etiology and the disparity in prostate cancer risk between black and white American men. Further studies are needed to confirm the high prostate cancer burden in African men and the role of genetics in prostate cancer etiology.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.juro.2014.04.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4332806PMC
September 2014

Clinical utility and impact of autopsies on clinical practice among doctors in a large teaching hospital in Ghana.

Glob Health Action 2014 3;7:23132. Epub 2014 Feb 3.

Department of Pathology, College of Health Sciences, University of Ghana Medical School, Korle-Bu, Accra, Ghana; Office of the Provost, College of Health Sciences, Korle-Bu, Accra, Ghana.

Background: Autopsies can provide a good indication of the quality of patient care, in terms of the accuracy of clinical diagnosis and the quality of treatment given.

Designs: This was a cross-sectional study among clinicians at the Korle-Bu Teaching Hospital (KBTH) in 2012. Data were collected with a 69-item, self-administered, structured questionnaire. A total of 215 questionnaires were sent out and 119 clinicians responded. Data were collected on the benefits and utility of autopsies for medical practice, care of patients, and management of clinical wards. Survey data were analyzed by simple descriptive statistics (i.e. proportions, ratios, and percentages). Data were analyzed using SPSS version 21.

Objective: This study examined the views of clinicians regarding the utility of autopsies and their influence on clinical practice in a large teaching hospital in Ghana.

Results: Overall, clinicians in KBTH agreed that autopsy reports are useful in answering clinical questions (55/119; 46.2%), confirming or verifying clinical diagnoses (54/119; 45.4%), providing information on unsuspected diagnoses (40/119; 33.6%), and for medical education (90/119; 75.6%). Overall, 70/119 (58.8%) of clinicians agreed that autopsy findings improve completeness and reliability of death certification and provide information on clinical effectiveness of treatment and patient management. However, only 23/119 (19.3%) of sampled clinicians had personal interactions with a pathologist during autopsy processes and 93/119 (78.2%) had not attended any autopsy demonstrations in the past 6 months. Attendance of pathologists at clinicopathological meetings of clinical departments of KBTH was minimal. Unfortunately, the use of autopsy reports for auditing clinical diagnostic performance was not seen as essential.

Conclusion: Strengthening the interaction between doctors and pathologists is essential in improving the autopsy process and utilization in the hospital. KBTH should create opportunities for doctors to attend autopsy demonstrations and for pathologists to attend clinicopathological meetings in the hospital.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3402/gha.v7.23132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3914029PMC
October 2014

A genome-wide association study of prostate cancer in West African men.

Hum Genet 2014 May 2;133(5):509-21. Epub 2013 Nov 2.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, 9609 Medical Center Drive, Rm 7-E106, MSC 9774, Bethesda, MD, 20892-9774, USA,

Age-adjusted mortality rates for prostate cancer are higher for African-American men compared with those of European ancestry. Recent data suggest that West African men also have elevated risk for prostate cancer relative to European men. Genetic susceptibility to prostate cancer could account for part of this difference. We conducted a genome-wide association study (GWAS) of prostate cancer in West African men in the Ghana Prostate Study. Association testing was performed using multivariable logistic regression adjusted for age and genetic ancestry for 474 prostate cancer cases and 458 population-based controls on the Illumina HumanOmni-5 Quad BeadChip. The most promising association was at 10p14 within an intron of a long non-coding RNA (lncRNA RP11-543F8.2) 360 kb centromeric of GATA3 (p = 1.29E-7). In sub-analyses, SNPs at 5q31.3 were associated with high Gleason score (≥7) cancers, the strongest of which was a missense SNP in PCDHA1 (rs34575154, p = 3.66E-8), and SNPs at Xq28 (rs985081, p = 8.66E-9) and 6q21 (rs2185710, p = 5.95E-8) were associated with low Gleason score (<7) cancers. We sought to validate our findings in silico in the African Ancestry Prostate Cancer GWAS Consortium, but only one SNP, at 10p14, replicated at p < 0.05. Of the 90 prostate cancer loci reported from studies of men of European, Asian or African-American ancestry, we were able to test 81 in the Ghana Prostate Study, and 10 of these replicated at p < 0.05. Further genetic studies of prostate cancer in West African men are needed to confirm our promising susceptibility loci.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00439-013-1387-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3988225PMC
May 2014

Breast cancer in Ghanaian women: what has changed?

Am J Clin Pathol 2013 Jul;140(1):97-102

Dept of Pathology, University of Ghana Medical School, PO Box 77, Korle-Bu, Accra, Ghana.

Objectives: To evaluate breast cancer in Ghanaian women and to compare these findings with those of previous studies by using histopathologic data.

Methods: A review of all breast cancer specimens from January 2005 through December 2009 in our institution was conducted.

Results: Of 4,109 female breast specimens reviewed, 1,342 (32.7%) were malignant. Mean (SD) patient age was 50.3 (13.3) years, and mean size of the primary tumors was 4.5 cm. Eighteen (1.3%) specimens were malignant phyllodes tumors. Significant positive associations were found between size of the primary tumor and histologic type (P = .01), histologic grade (P = .001), nodal involvement (P < .001), and TNM stage (P < .001).

Conclusions: More than 3 decades after the first publication of breast cancer in Ghanaian women, patients are still presenting with large clinically and histologically advanced invasive cancers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1309/AJCPW7TZLS3BFFIUDOI Listing
July 2013

AM Last Page. Medical education in Ghana.

Acad Med 2012 Feb;87(2):252

School of Medical Sciences, University of Cape Coast, Ghana.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/ACM.0b013e318245b9f2DOI Listing
February 2012

Cause of death among Ghanaian adolescents in Accra using autopsy data.

BMC Res Notes 2011 Sep 12;4:353. Epub 2011 Sep 12.

World Health Organization Country Office in Ghana, Accra, Ghana.

Background: There is limited data on adolescent mortality particularly from developing countries with unreliable death registration systems. This calls for the use of other sources of data to ascertain cause of adolescent mortality. The objective of this study was to describe the causes of death among Ghanaian adolescents 10 to 19 years in Accra, Ghana utilizing data from autopsies conducted in Korle Bu Teaching Hospital (KBTH).

Findings: Out of the 14,034 autopsies carried out from 2001 to 2003 in KBTH, 7% were among adolescents. Of the 882 deaths among adolescents analyzed, 402 (45.6%) were females. There were 365 (41.4%) deaths from communicable disease, pregnancy related conditions and nutritional disorders. Non-communicable diseases accounted for 362 (41%) cases and the rest were attributable to injuries and external causes of morbidity and mortality. Intestinal infectious diseases and lower respiratory tract infections were the most common communicable causes of death collectively accounting for 20.5% of total deaths. Death from blood diseases was the largest (8.5%) among the non-communicable conditions followed by neoplasms (7%). Males were more susceptible to injuries than females (χ2 = 13.45, p = .000). At least five out of ten specific causes of death were as a result of infections with pneumonia and typhoid being the most common. Sickle cell disease was among the top three specific causes of death. Among the females, 27 deaths (6.7%) were pregnancy related with most of them being as a result of abortion.

Conclusions: The autopsy data from the Korle-Bu Teaching Hospital can serve as a useful source of information on adolescent mortality. Both communicable and non-communicable diseases accounted for most deaths highlighting the need for health care providers to avoid complacency in their management of adolescents presenting with these diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/1756-0500-4-353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3180708PMC
September 2011

High prevalence of polyclonal hypergamma-globulinemia in adult males in Ghana, Africa.

Am J Hematol 2011 Jul 14;86(7):554-8. Epub 2011 Jun 14.

Division of Hematology, Department of Internal Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.

Chronic antigenic stimulation is associated with hypergamma-globulinemia. Higher rates of hypergamma-globulinemia in tropical populations are maintained even with migration to temperate regions. We conducted a population-based screening study to assess the prevalence and risk factors for hypergamma-globulinemia in Ghana, Africa. 917 Ghanaian males (50-74 years) underwent in-person interviews and health examinations. Serum from all persons was analyzed by electrophoresis performed on agarose gel; serum with a discrete/localized band was subjected to immunofixation. 54 persons with monoclonal proteins were excluded and 17 samples were insufficient for analysis. Using logistic regression and Chi-square statistics we analyzed patterns of hypergamma-globulinemia. Among 846 study subjects, the median γ-globulin level was 1.86 g/dL. On the basis of a U.S. reference, 616 (73%) had hypergamma-globulinemia (>1.6 g/dL) and 178 (21%) had γ-globulin levels >2.17 gm/dl. On multivariate analyses, lower education status (P = 0.0013) and never smoking (P = 0.038) were associated with increased γ-globulin levels. Self-reported history of syphilis was associated with hypergamma-globulinemia. We conclude that three quarters of this population-based adult Ghanaian male sample had hypergamma-globulinemia with γ-globulin levels >1.6 g/dL. Future studies are needed to uncover genetic and environmental underpinnings of our finding, and to define the relationship between hypergamma-globulinemia, monoclonal gammopathy of undetermined significance (MGUS), and multiple myeloma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajh.22040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3736856PMC
July 2011

Genome-wide association study of prostate cancer in men of African ancestry identifies a susceptibility locus at 17q21.

Nat Genet 2011 Jun 22;43(6):570-3. Epub 2011 May 22.

Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Norris Comprehensive Cancer Center, Los Angeles, California, USA.

In search of common risk alleles for prostate cancer that could contribute to high rates of the disease in men of African ancestry, we conducted a genome-wide association study, with 1,047,986 SNP markers examined in 3,425 African-Americans with prostate cancer (cases) and 3,290 African-American male controls. We followed up the most significant 17 new associations from stage 1 in 1,844 cases and 3,269 controls of African ancestry. We identified a new risk variant on chromosome 17q21 (rs7210100, odds ratio per allele = 1.51, P = 3.4 × 10(-13)). The frequency of the risk allele is ∼5% in men of African descent, whereas it is rare in other populations (<1%). Further studies are needed to investigate the biological contribution of this allele to prostate cancer risk. These findings emphasize the importance of conducting genome-wide association studies in diverse populations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/ng.839DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3102788PMC
June 2011

Unexpected elevated alanine aminotransferase, aspartate aminotransferase levels and hepatitis E virus infection among persons who work with pigs in accra, Ghana.

Virol J 2010 Nov 22;7:336. Epub 2010 Nov 22.

Department of Pathology, University of Ghana Medical School, College of Health Sciences, University of Ghana, Accra, Ghana.

Background: Several studies have suggested that elevated serum alanine aminotransferase (ALT) and asparte aminotransferase (AST) may be markers of hepatitis E virus (HEV) infection. Thus, individuals with elevated ALT and AST may have ongoing subclinical infection of HEV. We estimated the prevalence of anti-HEV antibodies and serum ALT and AST levels among persons who work with pigs in Accra, Ghana.

Results: Three hundred and fifty- persons who work with pigs provided blood samples for unlinked anonymous testing for the presence of antibodies to HEV, ALT and AST levels. The median age of participants was 32.85±11.38 years (range 15-70 years). HEV seroprevelance was 34.84%. Anti-HEV IgG was detected in 19.26% while anti-HEV IgM was detected in 15.58% of the persons who tested positive. On multivariate analysis, the independent determinants of HEV infection were, being employed on the farm for less than six months [odds ratio (OR) 8.96; 95% confidence interval (95% CI) 5.43-14.80], having piped water in the household and/or on the farm (OR 13.33; 95% CI 5.23-33.93) and consumption of alcohol (OR 4.91: 95% CI 2.65-9.10). Levels>3× the expected maximum were found for both ALT and AST among individuals who tested positive for anti-HEV IgG (ALT, 210.17±11.64 U/L; AST, 127.18±11.12 U/L) and anti-HEV IgM (ALT, 200.97±10.76 U/L; AST, 120.00±15.96 U/L).

Conclusion: Consistent with similar studies worldwide, the results of our studies revealed a high prevalence of HEV infection, ALT and AST values in pig handlers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/1743-422X-7-336DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2995795PMC
November 2010

Injury-related mortality among adolescents: findings from a teaching hospital's post mortem data.

BMC Res Notes 2010 May 5;3:124. Epub 2010 May 5.

World Health Organization Country Office in Ghana, Accra, Ghana.

Background: Injuries are noted to be an important cause of death among adolescents. There is however limited data on the injury related deaths among adolescents in Ghana.

Findings: Using data from post-mortem records derived from the Department of Pathology of the Korle-Bu Teaching Hospital (KBTH), Accra Ghana from 2001 to 2003, the causes of injury related deaths among adolescents 10 to 19 years were analyzed by gender and age groups 10 to 14 and 15 to 19 years. There were 151 injury-related deaths constituting 17% of the autopsies performed among adolescents in the study period. The male-to-female ratio was 2.1:1. Drowning was the most common cause of death (37%) in the study population. This was followed by road traffic accidents (RTA) (33%). Over 70% of the RTA victims were pedestrians knocked downed by a vehicle. Deaths from electrocution, poisoning, burns, stab/gunshot, hanging and other miscellaneous causes (example blast injury, traumatic injury from falling debris, fall from height) made up the remaining 30% of the injury related mortality. Among males and in both age categories, drowning was the leading cause of death. In females, the highest mortality was from road traffic accidents accounting for almost half (49%) of the deaths; significantly more than that occurring in males (25%, p = .004).

Conclusions: Findings from Korle-Bu Teaching Hospital post-mortem data on adolescents show that drowning and road traffic accidents are the leading causes of injury-related mortality. Appropriate injury reducing interventions are needed to facilitate a decrease in these preventable deaths.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/1756-0500-3-124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2874566PMC
May 2010

Bacterial contamination of blood and blood components in three major blood transfusion centers, Accra, Ghana.

Jpn J Infect Dis 2009 Jul;62(4):265-9

Department of Pathology, University of Ghana Medical School, College of Health Sciences, University of Ghana, Accra, Ghana.

Reports from studies conducted in several countries indicate a high incidence of bacterial contamination of donor blood. The prevalence of bacterial contamination of blood and its products in Ghana is not known. This study was conducted to determine the prevalence of bacterial contamination of blood and its products at the three major blood transfusion centers in the Greater Accra Region of Ghana. Stored whole blood and its products were cultured on different media, and isolates were identified using standard biochemical and bacteriological methods. The susceptibility of the isolates to selected antimicrobial agents was also determined by the disc diffusion method. The overall prevalence rate was 9% (28/303; whole blood, 13% [24/192]; plasma, 3% [2/79]; platelet, 9% [2/22]). The Gram-positive bacteria isolated were coagulase-negative Staphylococcus, S. aureus, and Bacillus spp., and the Gram-negative organisms were Yersinia enterocolitica, Citrobacter freundii, Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae. The Gram-positive bacteria were sensitive to cloxacillin, erythromycin, tetracycline, and gentamicin but resistant to penicillin, ampicillin, cefuroxime, and cotrimoxazole, while the Gram-negative bacteria were sensitive to amikacin and gentamicin but resistant to chloramphenicol, tetracycline, ampicillin, cefuroxime, cefotaxime (except Y. enterocolitica), and cotrimoxazole. Our results suggest that bacterial contamination of blood and its products is prevalent in Ghana.
View Article and Find Full Text PDF

Download full-text PDF

Source
July 2009

Hepatitis E virus infection is highly prevalent among pregnant women in Accra, Ghana.

Virol J 2009 Jul 20;6:108. Epub 2009 Jul 20.

Department of Pathology, University of Ghana Medical School, Accra, Ghana.

Background: Hepatitis E virus (HEV) is highly endemic in several African countries with high mortality rate among pregnant women. The prevalence of antibodies to HEV in Ghana is not known. Therefore we evaluated the prevalence of anti-HEV IgG and anti-HEV IgM among pregnant women seen between the months of January and May, 2008 at the Obstetrics and Gynaecology Department, Korle-Bu Teaching Hospital, Accra, Ghana.

Results: One hundred and fifty-seven women provided blood samples for unlinked anonymous testing for the presence of antibodies to HEV. The median age of participants was 28.89 +/- 5.76 years (range 13-42 years). Of the 157 women tested, HEV seroprevelance was 28.66% (45/157). Among the seropositive women, 64.40% (29/45) tested positive for anti-HEV IgM while 35.60% (16/45) tested positive to HEV IgG antibodies. HEV seroprevalence was highest (46.15%) among women 21-25 years of age, followed by 42.82% in = 20 year group, then 36.84% in = 36 year group. Of the 157 women, 75.79% and 22.92% were in their third and second trimesters of pregnancy, respectively. Anti-HEV antibodies detected in women in their third trimester of pregnancy (30.25%) was significantly higher, P < 0.05, than in women in their second trimester of pregnancy (25.0%).

Conclusion: Consistent with similar studies worldwide, the results of our studies revealed a high prevalence of HEV infection in pregnant women.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/1743-422X-6-108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2717077PMC
July 2009

Soluble factors from Plasmodium falciparum-infected erythrocytes induce apoptosis in human brain vascular endothelial and neuroglia cells.

Mol Biochem Parasitol 2008 Dec 19;162(2):172-6. Epub 2008 Sep 19.

Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, 720 Westview Drive SW, Atlanta, GA 30310, USA.

The severity of malaria is multi-factorial. It is associated with parasite-induced alteration in pro-inflammatory and anti-inflammatory cytokine and chemokine levels in host serum and cerebrospinal fluid. It is also associated with sequestration and cytoadherence of parasitized erythrocytes (pRBCs) in post-capillary venules and blood-brain barrier (BBB) dysfunction. The role of these factors in development of vascular injury and tissue damage in malaria patients is unclear. While some studies indicate a requirement for pRBC adhesion to vascular endothelial cells (ECs) in brain capillaries to induce apoptosis and BBB damage, others show no role of apoptosis resulting from adhesion of pRBC to EC. In the present study, the hypothesis that soluble factors from Plasmodium falciparum-infected erythrocytes induce apoptosis in human brain vascular endothelial (HBVEC) and neuroglia cells (cellular components of the BBB) was tested. Apoptotic effects of parasitized (pRBC) and non-parasitized erythrocyte (RBC) conditioned medium on HBVEC and neuroglia cells were determined in vitro by evaluating nuclear DNA fragmentation (TUNEL assay) in cultured cells. Soluble factors from P. falciparum-infected erythrocytes in conditioned medium induced extensive DNA fragmentation in both cell lines, albeit to a greater extent in HBVEC than neuroglia, indicating that extended exposure to high levels of these soluble factors in serum may be associated with vascular, neuronal and tissue injury in malaria patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.molbiopara.2008.09.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2671222PMC
December 2008
-->