Genomic testing in early localized prostate cancer may define subsets of African Americans with aggressive disease—a prospective study
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE209954 | GEO | 2022/07/29
REPOSITORIES: GEO
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Project description:BackgroundPersonalized genomic classifiers have transformed the management of prostate cancer (PCa) by identifying the most aggressive subsets of PCa. Nevertheless, the performance of genomic classifiers to risk classify African American men is thus far lacking in a prospective setting.MethodsThis is a prospective study of the Decipher genomic classifier for National Comprehensive Cancer Network low- and intermediate-risk PCa. Study-eligible non-African American men were matched to African American men. Diagnostic biopsy specimens were processed to estimate Decipher scores. Samples accrued in NCT02723734, a prospective study, were interrogated to determine the genomic risk of reclassification (GrR) between conventional clinical risk classifiers and the Decipher score.ResultsThe final analysis included a clinically balanced cohort of 226 patients with complete genomic information (113 African American men and 113 non-African American men). A higher proportion of African American men with National Comprehensive Cancer Network-classified low-risk (18.2%) and favorable intermediate-risk (37.8%) PCa had a higher Decipher score than non-African American men. Self-identified African American men were twice more likely than non-African American men to experience GrR (relative risk [RR] = 2.23, 95% confidence interval [CI] = 1.02 to 4.90; P = .04). In an ancestry-determined race model, we consistently validated a higher risk of reclassification in African American men (RR = 5.26, 95% CI = 1.66 to 16.63; P = .004). Race-stratified analysis of GrR vs non-GrR tumors also revealed molecular differences in these tumor subtypes.ConclusionsIntegration of genomic classifiers with clinically based risk classification can help identify the subset of African American men with localized PCa who harbor high genomic risk of early metastatic disease. It is vital to identify and appropriately risk stratify the subset of African American men with aggressive disease who may benefit from more targeted interventions.
| S-EPMC9745424 | biostudies-literature
Project description:Genomic testing in early localized prostate cancer may define subsets of African Americans with aggressive disease—a prospective study
| PRJNA863235 | ENA
Project description:This study aims to investigate the prevalence of the highly leukotoxic JP2 sequence versus the minimally leukotoxic non-JP2 sequence of Aggregatibacter actinomycetemcomitans within a cohort of 180 young African Americans, with and without localized aggressive periodontitis (LAP), in north Florida. The study included patients aged 5 to 25 y: 60 LAP patients, 60 healthy siblings (HS), and 60 unrelated healthy controls (HC). Subgingival plaque was collected from LAP sites-diseased (PD ≥5 mm with bleeding on probing) and healthy (PD ≤3 mm with no bleeding on probing)-and from healthy sites of HS and HC. Plaque DNA was extracted and analyzed by polymerase chain reaction for the detection of the JP2 and non-JP2 sequences of A. actinomycetemcomitans. Overall, 90 (50%) subjects tested positive for the JP2 sequence. Fifty (83.33%) LAP subjects were carriers of the highly leukotoxic JP2 sequence, detected in 45 (75%) diseased sites and 34 (56.67%) healthy sites. Additionally, JP2 carriage was found in 16 HS (26.67%) and 24 HC (40%; P < 0.0001, among groups). The non-JP2 sequence was detected in 26 (14.44%) total subjects: 17 (28.33%) LAP patients detected in equal amounts of diseased and healthy sites (n = 11, 18.33%), 6 (10%) HS sites, and 3 (5%) HC sites (P < 0.05, among groups). The JP2 sequence was strongly associated with LAP-diseased sites in young African Americans, significantly more so than the non-JP2 (ClinicalTrials.gov NCT01330719). Knowledge Transfer Statement: Clinicians may use the results of this study to identify susceptible individuals to aggressive periodontitis, potentially leading to more appropriate selection of therapeutic choices.
| S-EPMC5576056 | biostudies-literature
Project description:This study aimed to evaluate the potential risk for localized aggressive periodontitis (LAgP) in African American children by detection of the potential periodontal pathogen Aggregatibacter actinomycetemcomitans (Aa) using polymerase chain reaction (PCR) and microbiome analysis.Twenty-one pre-adolescents (age range equals 10.7 to 13.1 years old) were recruited, for this IRB-approved study. Oral examination included limited periodontal examination determining bleeding index (BOP) and periodontal probing (PD). An oral mucosa sample was used for analysis.Nine of 21 children were Aa+ by PCR. The Aa+ group had a significantly higher proportion of teeth with BOP and PD greater than four mm than the Aa- group (P=0.014 and 0.006 for percent BOP and percent PD equal to or greater than four mm, respectively; Mann Whitney Test). No significant differences in microbe abundance or composition were found from comparison of Aa+ versus Aa- samples.Detection of Aa from preadolescent African American children was associated with signs of periodontal inflammation. Although none of these children were diagnosed with LAgP, PCR targeting Aa could be a risk factor. Further study is indicated; however, the usefulness of PCR in dental practice setting to assess risk may be cost-effective for early diagnosis and prevention of LAgP.
| S-EPMC5682943 | biostudies-literature
Project description: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.
| S-EPMC8698937 | biostudies-literature
Project description:The present study investigated developmental pathways that can contribute to chronic disease among rural African Americans. With a sample of 342 African American youth (59% female) from the southeastern United States followed for nearly two decades (2001-2019), we examined the prospective association between family poverty during adolescence (ages 11-18) and insulin resistance (IR) in young adulthood (ages 25-29) as well as underlying biological and psychosocial mechanisms. Results indicated family poverty during adolescence forecast higher levels of IR in young adulthood, with accelerated immune cell aging at age 20 partially mediating this association. Serial mediational models confirmed the hypothesized pathway linking family poverty, perceived life chances, cellular aging, and IR. Findings provide empirical support for theorized developmental precursors of chronic disease.
| S-EPMC9427675 | biostudies-literature
Project description:Increasing COVID-testing and contact tracing is necessary to control the COVID-19 pandemic considering suboptimal vaccine rates. We conducted semi-structured interviews to explore views towards contact tracing and testing among 62 African Americans. Based on our findings, participants identified COVID-19 testing and contact tracing as beneficial, yet medical and governmental mistrust, stigma associated with SARS-CoV-2, lack of access, poor communication, and costs as major barriers. This study also highlights intervention targets to improve COVID-testing and contact tracing.
| S-EPMC8898856 | biostudies-literature
Project description:This was a prospective clinical trial testing the ability of gene expression models of drug sensitivity that were developed in human and canine cell lines and applied to outcomes in dogs treated with adjuvant carboplatin and/or doxorubicin. Tumor samples were collected prospectively, and gene expression analysis was conducted using Affymetrix Canine Genome 2.0 Arrays.
2021-07-20 | GSE180303 | GEO
Project description:This study provided the first examination of the psychometric properties of the 6-item Daily Spiritual Experiences Scale (DSES) in a large African American sample, the Jackson Heart Study (JHS). The JHS included measures of spiritual (DSES) and religious practices. Internal reliability, dimensionality, fit indices, and correlation were assessed. DSES scores reflected frequent daily spiritual experiences (12.84 ± 4.72) and reliability scores were high (? = 0.85; 95% CI 0.84-0.86). The DSES loaded on a single factor, with significant goodness-of-fit scores (RMSEA = 0.094, P < 0.01). Moderate significant correlations were noted among DSES items. Our findings confirm that the 6-item DSES had excellent psychometric properties in this sample.
| S-EPMC2888881 | biostudies-literature
Project description:BackgroundUterine fibroids are common. Symptoms are debilitating for many, leading to high medical and societal costs. Indirect data suggest that compared with white women, African Americans develop fibroids at least 10 years earlier on average, and their higher health burden has been well documented.ObjectiveThe objective of the study was to directly measure fibroid incidence and growth in a large, community-based cohort of young African-American women.Study designThis observational, community-based, prospective study enrolled 1693 African-American women, aged 23-35 years with no prior diagnosis of fibroids. Standardized transvaginal ultrasound examinations at enrollment and after approximately 18 months were conducted to identify and measure fibroids ≥0.5 cm in diameter. Fibroid growth (change in natural log volume per 18 months) was analyzed with mixed-model regression (n = 344 fibroids from 251 women whose baseline ultrasound revealed already existing fibroids).ResultsAmong the 1123 fibroid-free women with follow-up data (88% were followed up), incidence was 9.4% (95% confidence interval, 7.7-11.2) and increased with age (Ptrend < .0001), from 6% (confidence interval, 3-9) for 23-25 year olds to 13% (confidence interval, 9-17) for 32-35 year olds. The chance of any new fibroid development was greater than twice as high for women with existing fibroids compared with women who were fibroid free at baseline (age-adjusted relative risk = 2.3 (confidence interval, 1.7-3.0). The uterine position of most incident fibroids (60%) was intramural corpus. Average fibroid growth was 89% per 18 months (confidence interval, 74-104%) but varied by baseline fibroid size (P < .0001). Fibroids ≥2 cm in diameter had average growth rates well under 100%. In contrast, small fibroids (<1 cm diameter) had an average growth rate of nearly 200% (188%, confidence interval, 145-238%). However, these small fibroids also had a high estimated rate of disappearance (23%).ConclusionThis is the first study to directly measure age-specific fibroid incidence with a standardized ultrasound protocol and to measure fibroid growth in a large community-based sample. Findings indicate that very small fibroids are very dynamic in their growth, with rapid growth, but a high chance of loss. Larger fibroids grow more slowly. For example, a 2-cm fibroid is likely to take 4-5 years to double its diameter. Detailed data on fibroid incidence confirm an early onset in African-American women.
| S-EPMC8039858 | biostudies-literature