Lipid Alterations in African American Men with Prostate Cancer

African-American (AA) men are more than twice as likely to die of prostate cancer (PCa) than European American (EA) men. Previous in silico analysis revealed enrichment of altered lipid metabolic pathways in pan-cancer AA tumors. Here, we performed global unbiased lipidomics profiling on 48 matched localized PCa and benign adjacent tissues (30 AA, 24 ancestry-verified, and 18 EA, 8 ancestry verified) and quantified 429 lipids belonging to 14 lipid classes. Significant alterations in long chain polyunsaturated lipids were observed between PCa and benign adjacent tissues, low and high Gleason tumors, as well as associated with early biochemical recurrence, both in the entire cohort, and within AA patients. Alterations in cholesteryl esters, and phosphatidyl inositol classes of lipids delineated AA and EA PCa, while the levels of lipids belonging to triglycerides, phosphatidyl glycerol, phosphatidyl choline, phosphatidic acid, and cholesteryl esters distinguished AA and EA PCa patients with biochemical recurrence. These first-in-field results implicate lipid alterations as biological factors for prostate cancer disparities.

A primer on hypertension and on the racial / ethnic disparities in diagnosis and management: a comprehensive overview

Hypertension is a major cause of premature death worldwide, where it contributes to stroke, cardiovascular and renal disease. Forty percent of adults aged 30-79 years worldwide have hypertension, two-thirds of whom are living in low and middle-income countries. Most adults with hypertension are not fully aware that they have the condition, therefore it often goes ignored and untreated. Of the 1.28 billion people worldwide, who have been reported to have hypertension, data indicates that one in five females and one in four males are included in that estimate. Moreover, data from World Health Organization reports that less than half of adults (42%) with hypertension are diagnosed and treated adequately and approximately only one in five adults (21%) with hypertension have it under adequate control. One of the worldwide goals for non-communicable diseases is to scale back the prevalence of hypertension by 33% between 2010 and 2030. In African Americans, readily available thiazide diuretics or Calcium Channel Blockers (CCBs) have been shown to be more effective in lowering blood pressure than Renin Angiotensin System inhibitors (RAS) or β-adrenergic blockers and are also more effective in reducing cardiovascular disease (CVD) events than RAS inhibitors or adrenergic blockers. The ethnical difference in hypertension and hypertension- related complaint issues are associated with lesser mortality and morbidity pitfalls compared with their white counterparts. These redundant pitfalls from elevated blood pressure have a dramatic effect on life expectancy and career productivity for African American men and women and which is significantly lower than has been reported for Caucasian Americans of either gender. These present challenges remain to be completely understood and give a result to overcome ethnical and racial differences in the frequency and treatment of hypertension. Social determinants of health similar as educational status, access to health care and low income play a crucial part in frequency and blood pressure control rates. Development of appropriate health care programs at the state and public situations to address these issues will be essential to reduce these differences. Thus, the purpose of this paper is to review the prevalence and ethnic disparities in the diagnosis and treatment of hypertension and to suggest steps to improve the outcomes.

Considering Predictive Factors in the Diagnosis of Clinically Significant Prostate Cancer in Patients with PI-RADS 3 Lesions

The use of multi-parametric magnetic resonance imaging (mpMRI) in conjunction with the Prostate Imaging Reporting and Data System (PI-RADS) is standard practice in the diagnosis, surveillance, and staging of prostate cancer. The risk associated with lesions graded at a PI-RADS score of 3 is ambiguous. Further characterization of the risk associated with PI-RADS 3 lesions would be useful in guiding further work-up and intervention. This study aims to better characterize the utility of PI-RADS 3 and associated risk factors in detecting clinically significant prostate cancer. From a prospectively maintained IRB-approved dataset of all veterans undergoing mpMRI fusion biopsy at the Southeastern Louisiana Veterans Healthcare System, we identified a cohort of 230 PI-RADS 3 lesions from a dataset of 283 consecutive UroNav-guided biopsies in 263 patients from October 2017 to July 2020. Clinically significant prostate cancer (Gleason Grade ≥ 2) was detected in 18 of the biopsied PI-RADS 3 lesions, representing 7.8% of the overall sample. Based on binomial analysis, PSA densities of 0.15 or greater were predictive of clinically significant disease, as was PSA. The location of the lesion within the prostate was not shown to be a statistically significant predictor of prostate cancer overall (p = 0.87), or of clinically significant disease (p = 0.16). The majority of PI-RADS 3 lesions do not represent clinically significant disease; therefore, it is possible to reduce morbidity through biopsy. PSA density is a potential adjunctive factor in deciding which patients with PI-RADS 3 lesions require biopsy. Furthermore, while the risk of prostate cancer for African-American men has been debated in the literature, our findings indicate that race is not predictive of identifying prostate cancer, with comparable Gleason grade distributions on histology between races.

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

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.

Social Determinants of Men’s Health Across the Life Course

There is a paucity of research focusing on the complex interaction between social, behavioral, biological, and psychosocial factors, and health outcomes among men. This symposium contains a collection of papers that discuss some key social determinants of health (SDOH) that can provide insights to advance our understanding of men’s health and aging across the life course. Dawn will discuss the Stroke Counseling for Risk Reduction (SCORRE) intervention designed to increase awareness, risk perceptions, and health behaviors to reduce stroke risk in African Americans. Findings suggest tailoring the intervention to the needs and preferences of young African American men. Archibald and colleagues seek to determine if race differences in allostatic load (AL) among adult men vary by age. Black men 45-64 had a higher AL score (PR = 1.14, 95% CI 1.02, 1.28) than White men. Skipper and colleagues used a grounded theory approach to examine the negative interactions of 35 religious middle and old age Black men. Analyses reveal that church-related negative interactions broadly fall within the following themes: (1) ageism within intergenerational churches, (2) people are messy, and (3) issues with leadership. Bruce and colleagues examine the association between religious service attendance and mortality among Black men. Participants who attended at least once per week were 18% less likely to die than their peers who did not attend a religious service at all (HR 0.82; 95% CI 0.68-0.99). These presentations collectively will bolster our knowledge on key SDOH among men across the life course.

Tailoring Stroke Counseling for Risk Reduction Intervention to African American Men

Early life course achievement and maintenance of ideal cardiovascular health is associated with reduced risk of developing stroke later in life. The Stroke Counseling for Risk Reduction (SCORRE) intervention is an age-and-culturally relevant intervention originally designed to correct inaccurate stroke risk perceptions and improve lifestyle behaviors to reduce stroke risk in AAs age 20-35. In a study testing SCORRE, fewer men participated, but most were not at a stage of readiness for behavior change; many did not think they were at risk despite averaging three modifiable risk factors, and while improvements in outcomes were observed in women they were not in men. These differences led to tailoring SCORRE to young AA men. The methods for tailoring SCORRE and resulting strategies for attracting, engaging, and empowering them towards stroke risk reduction, including hypotheses concerning food supply, housing, economic and social relationships, education, and mental health care will be raised for discussion.

Coming Back Home to Oppressive Mississippi: A Figurative Study of Jesmyn Ward’s Men We Reaped

The aim of the paper is to discuss the figurative aspects of Jesmyn Ward’s The Men We Reaped (2013). In her memoir, Ward demonstrates the connections between the systemic racism in the US South and the tragic stories of five African-American men who were close to her, and who died between 2000-2004. The tragic loss of these lives is presented through a number of figurative images which present the region through the metaphors of predatory animals, physical burdens and uncanny doubling. Also, the article reflects on how Ward coped with the trauma of loss through her writings, and how, in numerous interviews, she justified her decision to return home to Mississippi and to settle there, in spite of the systemic racism and the trauma of loss.