scholarly journals Epigenome-Wide Association Study of Prostate Cancer in African Americans Identifies DNA Methylation Biomarkers for Aggressive Disease

Biomolecules ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1826
Author(s):  
Yifan Xu ◽  
Chia-Wen Tsai ◽  
Wen-Shin Chang ◽  
Yuyan Han ◽  
Maosheng Huang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Dna Methylation ◽  
African American ◽  
African Americans ◽  
Zinc Finger Protein ◽  
African American Men ◽  
Pathway Enrichment Analysis ◽  
Cpg Sites ◽  
Differentially Methylated Genes ◽  
Incidence And Mortality

DNA methylation plays important roles in prostate cancer (PCa) development and progression. African American men have higher incidence and mortality rates of PCa than other racial groups in U.S. The goal of this study was to identify differentially methylated CpG sites and genes between clinically defined aggressive and nonaggressive PCa in African Americans. We performed genome-wide DNA methylation profiling in leukocyte DNA from 280 African American PCa patients using Illumina MethylationEPIC array that contains about 860K CpG sties. There was a slight increase of overall methylation level (mean β value) with the increasing Gleason scores (GS = 6, GS = 7, GS ≥ 8, P for trend = 0.002). There were 78 differentially methylated CpG sites with P < 10−4 and 9 sites with P < 10−5 in the trend test. We also found 77 differentially methylated regions/genes (DMRs), including 10 homeobox genes and six zinc finger protein genes. A gene ontology (GO) molecular pathway enrichment analysis of these 77 DMRs found that the main enriched pathway was DNA-binding transcriptional factor activity. A few representative DMRs include HOXD8, SOX11, ZNF-471, and ZNF-577. Our study suggests that leukocyte DNA methylation may be valuable biomarkers for aggressive PCa and the identified differentially methylated genes provide biological insights into the modulation of immune response by aggressive PCa.

scholarly journals Prostate Cancer Incidence and Mortality in Barbados, West Indies

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Anselm J. M. Hennis ◽  
Ian R. Hambleton ◽  
Suh-Yuh Wu ◽  
Desiree H.-A. Skeete ◽  
Barbara Nemesure ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
African American ◽  
Cancer Incidence ◽  
West Indies ◽  
African American Men ◽  
Mortality Rates ◽  
Prostate Cancer Incidence ◽  
White American ◽  
Incidence And Mortality ◽  
The Us

We describe prostate cancer incidence and mortality in Barbados, West Indies. We ascertained all histologically confirmed cases of prostate cancer during the period July 2002 to December 2008 and reviewed each death registration citing prostate cancer over a 14-year period commencing January 1995. There were 1101 new cases for an incidence rate of 160.4 (95% Confidence Interval: 151.0–170.2) per 100,000 standardized to the US population. Comparable rates in African-American and White American men were 248.2 (95% CI: 246.0–250.5) and 158.0 (95% CI: 157.5–158.6) per 100,000, respectively. Prostate cancer mortality rates in Barbados ranged from 63.2 to 101.6 per 100,000, compared to 51.1 to 78.8 per 100,000 among African Americans. Prostate cancer risks are lower in Caribbean-origin populations than previously believed, while mortality rates appeared to be higher than reported in African-American men. Studies in Caribbean populations may assist understanding of disparities among African-origin populations with shared heredity.

scholarly journals Correlating blood-based DNA methylation markers and prostate cancer risk in African-American men

PLoS ONE ◽  
2018 ◽  
Vol 13 (9) ◽  
pp. e0203322 ◽  
Author(s):  
Emmanuel Moses-Fynn ◽  
Wei Tang ◽  
Desta Beyene ◽  
Victor Apprey ◽  
Robert Copeland ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Dna Methylation ◽  
African American ◽  
Cancer Risk ◽  
African American Men ◽  
Prostate Cancer Risk

Duffy Antigen/Receptor for Chemokines (DARC): Is There a Role in Prostate Cancer?.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4394-4394
Author(s):  
Samuel B. Anyona ◽  
Shiyan Zheng ◽  
Thomas Wheeler ◽  
Michael Ittmann ◽  
Teresa G. Hayes ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
African American ◽  
African Americans ◽  
African American Men ◽  
Rapid Development ◽  
Antigen Receptor ◽  
Taqman Assay ◽  
Blood Group Antigens ◽  
Duffy Antigen ◽  
Duffy Negative

Abstract Introduction: The Duffy blood group antigens function as chemokine receptors and as receptors for several species of malarial parasites. Approximately 70% of African Americans are Duffy negative as a result of a single nucleotide polymorphism in the promoter region of the Duffy antigen/receptor for chemokines (DARC) gene in a consensus-binding site for GATA 1. This mutation abolishes the promoter activity in erythrocytes, impairing the expression of DARC on red blood cells. Other than resistance to certain species of malaria, the functional consequence of Duffy negativity is unclear; however, it has recently been proposed that the Duffy antigen acts as a biological ‘sink’ to clear pro-inflammatory chemokines from tissue microcirculation. Further it has been suggested that since the incidence of prostate cancer in African Americans is 60% higher than in Caucasians, absence of the Duffy antigen might predispose African Americans to prostate cancer by impairing downregulation of proinflammatory cytokines. We tested the hypothesis that lack of expression of DARC on erythrocytes predisposes African American men to develop prostate cancer. Methods: We conducted a case control study of 89 African American men with confirmed prostate cancer and 51 age matched healthy African American men. The samples were genotyped for the promoter polymorphism using an allele specific real time PCR assay (Taqman assay) developed for this study. Results: The frequency of the Duffy negative allele was 75.8% among the patients and 81.4% among the controls (odds ratio = 0.72, p value = 0.28). The distribution of heterozygous and homozygous Duffy negative patients did not differ between the cases and controls. Conclusion: It has been suggested that individuals lacking erythrocyte expression of DARC have higher prostate levels of angiogenic chemokines that might promote more rapid development of prostate cancer. The data presented here found no difference in the frequency of the Duffy negative allele between African American men with prostate cancer and healthy age matched African American controls. Since several studies suggest that polymorphisms associated with differential production of IL-8, IL-10 and VEGF are risk factors for prostate cancer, it remains possible that a polymorphism associated with differential cytokine production in combination with Duffy negativity increases the risk for prostate cancer.

scholarly journals Differential DNA methylation landscape in skin fibroblasts from African Americans with systemic sclerosis

2020 ◽  
Author(s):  
DeAnna Baker Frost ◽  
Willian da Silveira ◽  
E. Starr Hazard ◽  
Ilia Atanelishvili ◽  
Robert C Wilson ◽  
...  
Keyword(s):  
Dna Methylation ◽  
African American ◽  
Systemic Sclerosis ◽  
African Americans ◽  
African Ancestry ◽  
Ethnic Disparities ◽  
Differential Methylation ◽  
Dermal Fibroblasts ◽  
Skin Fibroblasts ◽  
Cpg Sites

Objective. The etiology and reasons underlying the ethnic disparities in systemic sclerosis (SSc) remain unknown. African Americans are disproportionally affected by SSc, yet underrepresented in research. The aim of this study was to comprehensively investigate the association of DNA methylation levels with SSc in dermal fibroblasts from patients of African ancestry. Methods. Reduced representation bisulfite sequencing (RRBS) was performed on primary cultured dermal fibroblasts from 15 SSc patients and 15 controls of African ancestry, and over 3.8 million CpG sites were tested for differential methylation patterns between cases and controls. Gene set enrichment (GSEA) and gene ontology (GO) analyses were computed to elucidate the underlying biological processes. Quantitative PCR (qPCR) was performed to assess correlations between DNA methylation changes and gene expression levels of top candidate genes. Results. Skin fibroblasts from African American patients exhibited widespread reduced DNA methylation. Differentially methylated CpG sites were most enriched in introns and intergenic regions, while depleted in 5′ UTR, promoters, and CpG islands. Seventeen genes and eleven promoters showed significant differential methylation, mostly in non-coding RNA genes and pseudogenes. GSEA and GO enrichment analysis revealed enrichment of immune, metabolism, cell development, and cell signaling pathways, including those related to interferon signaling and mesenchymal differentiation. The hypomethylation of DLX5 and TMEM140 was accompanied by these genes′ overexpression, while for the lncRNA MGC12916, it was accompanied by its under-expression in patients. Conclusion. These data show that differential methylation occurs in dermal fibroblasts from African American patients with SSc and identifies novel coding and non-coding genes.

scholarly journals Using Genetic Burden Scores for Gene-by-Methylation Interaction Analysis on Metabolic Syndrome in African Americans

2019 ◽  
Vol 21 (3) ◽  
pp. 279-285
Author(s):  
Jacquelyn Y. Taylor ◽  
Erin B. Ware ◽  
Michelle L. Wright ◽  
Jennifer A. Smith ◽  
Sharon L. R. Kardia
Keyword(s):  
Metabolic Syndrome ◽  
Dna Methylation ◽  
Data Analysis ◽  
African Americans ◽  
Multiple Testing ◽  
African American Men ◽  
Interaction Analysis ◽  
Association Studies ◽  
Cpg Sites ◽  
Genetic Burden

With the rapid advancement of omics-based research, particularly big data such as genome- and epigenome-wide association studies that include extensive environmental and clinical variables, data analytics have become increasingly complex. Researchers face significant challenges regarding how to analyze multifactorial data and make use of the findings for clinical translation. The purpose of this article is to provide a scientific exemplar for use of genetic burden scores as a data analysis method for studies with both genotype and DNA methylation data in which the goal is to evaluate associations with chronic conditions such as metabolic syndrome (MetS). This study included 739 African American men and women from the Genetic Epidemiology Network of Arteriopathy Study who met diagnostic criteria for MetS and had available genetic and epigenetic data. Genetic burden scores for evaluated genes were not significant after multiple testing corrections, but DNA methylation at 2 CpG sites (dihydroorotate dehydrogenase cg22381196 pFDR = .014; CTNNA3 cg00132141 pFDR = .043) was significantly associated with MetS after controlling for multiple comparisons. Interactions between the marginally significant CpG sites and burden scores, however, were not significant. More work is required in this area to identify intermediate biological pathways influenced by environmental, genetic, and epigenetic variation that may explain the high prevalence of MetS among African Americans. This study does serve, however, as an example of the use of the genetic burden score as an alternative data analysis approach for complex studies involving the analysis of genetic and epigenetic data simultaneously.

Genomic variations associated with prostate cancer in large cohort of African American men.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 20-20
Author(s):  
Rayford Walter ◽  
Jennifer Jordan ◽  
Mandeep Takhar ◽  
Mohammed Alshalalfa ◽  
Darlene Dai ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Dna Repair ◽  
African American ◽  
Racial Disparities ◽  
African American Men ◽  
Race Model ◽  
Immune Infiltration ◽  
Incidence And Mortality ◽  
Pan Cancer

20 Background: Racial disparities in prostate cancer (PCa) incidence and mortality are well known. PCa is known to be more aggressive in African American men (AAM) in terms of higher incidence and mortality rates. Here we validate a tumor gene expression pan-cancer race model in men with PCa and further characterize genomic differences that may contribute to disparate clinical outcomes Methods: We obtained de-identified genome-wide expression profiles from clinical use of the Decipher RP test in 9,953 men from the GRID registry database. A subset of men (n = 313) had known race status. A pan-cancer race model, developed to predict patient AAM race from analysis of gene expression patterns in 4,162 tumors from retrospective cohorts with known race status was applied to the prospective cohort for race prediction. Gene expression data was used to define genomic differences. Results: The race model has an AUC of 0.98 discriminating EAM from AAM in independent PCa cohort. The model was then applied to the 9,640 GRID patients with unknown race status and classified 6,831 as EAM, 1,058 as AAM with 1,751 as having indeterminate race. Characterizing the molecular subtypes, we found known and predicted AAM to be enriched with SPINK1+ tumors (21% and 24%, respectively) compared to predicted EAM (8%). In contrast, while ERG+ was found 22% and 19% in known and predicted AAM, respectively compared to 46% in predicted EAM. Based on PAM50 prostate cancer classifier, 61% of AAM were classified as basal-like tumors, whereas 41% were basal-like in EAM. Similarly, 28% of AAM had low AR-A while only 11% of EAM had low AR-A. AAM tumors had higher levels of immune infiltration signatures as well as higher scores for inflammatory and interferon gamma responses, and Interleukin 6 (IL6) signaling activity scores. AAM had lower DNA repair and glycolysis pathway activity compared to EAM Conclusions: Known and predicted AAM, were enriched with SPINK1+ tumors, higher immune infiltration and activation but lower ERG+, DNA repair and AR activity tumors. Using such large GRID data with known race, we will further understand the underlying causes associated with prostate cancer racial disparities which could lead to personalized diagnosis and treatment.

scholarly journals Prostate Cancer Incidence Rates in Africa

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Lisa W. Chu ◽  
Jamie Ritchey ◽  
Susan S. Devesa ◽  
Sabah M. Quraishi ◽  
Hongmei Zhang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
African American ◽  
African Americans ◽  
Cancer Incidence ◽  
African American Men ◽  
Population Based ◽  
Incidence Rates ◽  
International Agency ◽  
Prostate Cancer Incidence ◽  
Cancer Incidence Rates

African American men have among the highest prostate cancer incidence rates in the world yet rates among their African counterparts are unclear. In this paper, we compared reported rates among black men of Sub-Saharan African descent using data from the International Agency for Research on Cancer (IARC) and the National Cancer Institute Surveillance, Epidemiology, and End Results Program for 1973–2007. Although population-based data in Africa are quite limited, the available data from IARC showed that rates among blacks were highest in the East (10.7–38.1 per 100,000 man-years, age-adjusted world standard) and lowest in the West (4.7–19.8). These rates were considerably lower than those of 80.0–195.3 observed among African Americans. Rates in Africa increased over time (1987–2002) and have been comparable to those for distant stage in African Americans. These patterns are likely due to differences between African and African American men in medical care access, screening, registry quality, genetic diversity, and Westernization. Incidence rates in Africa will likely continue to rise with improving economies and increasing Westernization, warranting the need for more high-quality population-based registration to monitor cancer incidence in Africa.

scholarly journals Prostate Cancer Screening in African American Men: Barriers and Methods for Improvement

2008 ◽  
Vol 2 (2) ◽  
pp. 172-177 ◽  
Author(s):  
Diane Reynolds
Keyword(s):  
Prostate Cancer ◽  
African American ◽  
Cancer Screening ◽  
Access To Health Care ◽  
African American Men ◽  
Prostate Cancer Screening ◽  
Medical Profession ◽  
Inadequate Knowledge ◽  
Incidence And Mortality ◽  
Caucasian Men

African American men have the highest rate of incidence for prostate cancer in the world and are more likely to die from the disease than other ethnic groups (National Institutes of Health, 1996). Routine screening for prostate cancer can lead to early detection of the disease, thereby reducing negative outcomes, but studies have shown that African American men are less likely than Caucasian men to engage in screening practices. Lack of access to health care, socioeconomic status, inadequate knowledge, fear, patient-provider communication, distrust of the medical profession, and aversion to digital rectal exam have been identified as possible barriers to prostate cancer screening in African American men. This literature review explores causes of this striking disparity between prostate cancer incidence and mortality in African American men and cites strategies used to improve prostate cancer screening rates among this population.

scholarly journals Lack of Comprehension of Common Prostate Cancer Terms in an Underserved Population

2009 ◽  
Vol 27 (12) ◽  
pp. 2015-2021 ◽  
Author(s):  
Kerry L. Kilbridge ◽  
Gertrude Fraser ◽  
Murray Krahn ◽  
Elizabeth M. Nelson ◽  
Mark Conaway ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
African American ◽  
Informed Consent ◽  
Patient Education ◽  
Low Income ◽  
African American Men ◽  
Reading Level ◽  
Cancer Knowledge ◽  
Prostate Cancer Knowledge ◽  
Incidence And Mortality

Purpose To assess the comprehension of common medical terms used in prostate cancer in patient education materials to obtain informed consent, and to measure outcomes after prostate cancer treatment. We address this issue among underserved, African-American men because of the increased cancer incidence and mortality observed in this population. Patients and Methods We reviewed patient education materials and prostate-specific quality-of-life instruments to identify technical terms describing sexual, urinary, and bowel function. Understanding of these terms was assessed in face-to-face interviews of 105, mostly African-American men, age ≥ 40, from two low-income clinics. Comprehension was evaluated using semiqualitative methods coded by two independent investigators. Demographics were collected and literacy was measured. Results Fewer than 50% of patients understood the terms “erection” or “impotent.” Only 5% of patients understood the term “incontinence” and 25% understood the term “bowel habits.” More patients recognized word roots than related terms or compound words (eg, “rectum” v “rectal urgency,” “intercourse” v “vaginal intercourse”). Comprehension of terms from all domains was statistically significantly correlated with reading level (P < .001). Median literacy level was fourth to sixth grade. Prostate cancer knowledge was poor. Many patients had difficulty locating key anatomic structures. Conclusion Limited comprehension of prostate cancer terms and low literacy create barriers to obtaining informed consent for treatment and to measuring prostate cancer outcomes accurately in our study population. In addition, the level of prostate cancer knowledge was poor. These results highlight the need for prostate cancer education efforts and outcomes measurements that consider literacy and use nonmedical language.

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