AA Men Research Articles

Racial disparities in an aging population: the relationship between age and race in the management of African American men with high-risk prostate cancer.

To evaluate the relationship between age and race on the receipt of definitive therapy among men with high-risk prostate cancer (CaP). We used the Surveillance, Epidemiology and End Results Program to identify 62,644 men with high-risk CaP (PSA >20 or Gleason 8-10 or stage ≥cT3a) diagnosed from 2004 to 2010. Multivariable logistic regression analysis modeled the interaction between age and race and its association with receipt of definitive therapy on 57,674 patients (47,879 white men; 9,795 African American [AA] men) with complete data on the covariates of interest. Among men age ≥70, AA men had a higher risk of CaP-specific mortality (PCSM) compared to white men after adjusting for sociodemographic and prostate cancer-specific factors (Adjusted HR 1.20; 95% CI 1.02-1.38; P=0.02). Nevertheless, a significant interaction between race and age was found (Pinteraction=0.01), such that the adjusted odds of receiving definitive treatment for AA vs. white was 0.67 (95% CI 0.62-0.73; P<0.001) among men age <70, but was 0.60 (95% CI 0.55-0.66; P<0.001) among men age ≥70, suggesting increased racial disparity in the receipt of definitive treatment among older men. AA men with high-risk CaP are less likely to receive definitive therapy than white men. This disparity is significantly larger among men age ≥70, despite excess PCSM among AA men in this group. With a rapidly expanding population of older minority men, this disparity should be urgently addressed to prevent increasing disparities in cancer care.

Biopsy Criteria for Determining Appropriateness for Active Surveillance in the Modern Era

To evaluate algorithms to predict insignificant prostate cancer at radical prostatectomy (RP). Five hundred and fifty men (410 Caucasian, 100 African American [AA], and 40 others) with prostate-specific antigen (PSA) level <10 ng/dL, T1c, 12-core biopsy, and biopsy Gleason score 3 + 3 = 6 were categorized into training and validation sets. Six biopsy algorithms were tested for predicting insignificant (0.5 cm(3), organ confined, and Gleason score ≤6) cancer at RP. Cancers incorrectly predicted to be insignificant were ranked into 4 groups of increasing aggressiveness. Original (Gleason score ≤6, PSA density ≤0.15, ≤2 positive cores, and maximum core involvement ≤50%) and modified Epstein criteria (Gleason score ≤6, PSA density ≤0.15, ≤2 positive cores, and unilateral cancer) had the highest negative predictive values-correct classification of insignificant cancer. Among cancers predicted to be insignificant in Caucasians, 29.9% cases using the original and 27% cases using the modified Epstein criteria had significant cancer at RP. However, more adverse findings at RP were misclassified as insignificant in only 3.5% and 2.2% of cases using the original and modified Epstein criteria, respectively. Of cancers predicted insignificant in AA men, 54.1% cases using the original and 51.6% cases using the modified Epstein criteria were misclassified as insignificant. Dominant anterior tumors were seen in 117 Caucasian (28.5%) and 44 AA men (44%). The Epstein criteria maintain their accuracy in the modern era with extended biopsy sampling. The negative predictive values are lower in AA men, in part due to higher frequency of anterior tumors, where multiparametric magnetic resonance imaging should be recommended in AAs considering surveillance.

Abstract P272: Cumulative Risk for Hypercholesterolemia In Middle-Aged White and African American Men and Women

Introduction: The long-term risks for incident hypercholesterolemia (HC) have not been quantified by sex in AA men and women. Methods: We conducted an individual-level pooled analysis of participants from The Atherosclerosis Risk in Communities and The Framingham Offspring Studies with baseline prevalence and follow-up data on HC and lipid-lowering medications. Hypercholesterolemia was defined as a total cholesterol level &gt; 240mg/dL or the use of lipid-lowering medications on ≥2 consecutive examinations. We quantified the long-term risk for HC using competing risk models to assess incidence from age 55 years (y) though 70y to 85y, adjusted for baseline prevalence and competing risks of death. Analyses were stratified by race and sex. Results: There were 11,341 White and 2,828 AA participants (55% and 63% female, respectively) included in the analysis. At an index age of 55y the mean (SD) BMIs in White and AA (men/women) respectively were: 27.8(4.1)/26.9 (5.6) and 28.1(5)/31.3(6.7)Kg/m2. Baseline prevalence rates of HC were not substantially different across race and sex groups. White women had the highest risks for the development of HC, with long-term risks as high has 63% through age 80y. AA men had the lowest risks for hypercholesterolemia through at 70y. Conclusions: The burden of HC is substantial across all race groups, with the highest risks found in white women. Aggressive surveillance and early preventive efforts against HC are needed across all race and sex groups.

Monitoring of health-related quality of life and symptoms in prostate cancer survivors: a randomized trial

Routine symptom and health-related quality of life (HRQOL) assessments can engage patients, give provider feedback, and improve doctor/patient communication. We compared the impact of a technology-assisted symptom monitoring system versus usual care on HRQOL and doctor/patient communication in early-stage prostate cancer (PCa) survivors. Men (N = 94) were on average 62-years old, mostly African American (AA; 61.7%), and 10-19 months post-treatment. They were randomized to symptom monitoring plus feedback (SM + F; n = 49) or usual care (UC; n = 45). SM+F participants completed a 12-item telephoneassisted monitoring intervention. All participants completed a baseline and 2 follow-up interviews. Among the SM+F participants, perceptions of the monitoring system were positive: 97.1% endorsed it as easy/very easy to use and 85% felt all patients could benefit from it. At baseline, men reported favorable general and cancer-specific HRQOL and doctor/patient communication, but poorer urinary and sexual function. Although there was no overall impact of the intervention, post hoc exploratory analyses indicated that among AA men, those who received SM+F improved relative to UC on doctor/patient communication (P < .05), general HRQOL (P < .06), and sexual function (P < .05). Variability in survivor follow-up care, limited access to eligible participants, and minimal physician training in the use of reports likely decreased physician investment. Overall, PCa survivors were receptive to this monitoring system. Exploratory analyses suggest that this technology-assisted monitoring system may be of particular benefit to African American men. Additional studies with larger samples, more intervention time-points, and increased physician training are needed to strengthen the intervention's impact.

In Vacuo Synthesis of Xanthan-gum-based Hydrogels with Different Vinyl Monomer Mixtures and their Swelling Behaviour in Response to External Environmental Conditions

This research paper deals with the in vacuo synthesis of pH- and temperature-sensitive hydrogels of xanthan gum with different vinyl monomer mixtures such as acrylamide-co-acrylic acid (AAm-co-AA), acrylamide-co-acrylonitrile (AAm-co-AN), and acrylamide-co-methacrylic acid (AAm-co-MAA), keeping acrylamide as the principal monomer. Different optimised reaction parameters for the graft copolymerisation of xanthan gum (Gx) with AAm were as follows: reaction time = 240 min; temperature = 60°C; amount of water = 25 mL; vacuum = 450 mmHg; pH = 7.0; [KPS] = 0.0068 mol L-1; [AAm] = 0.071 mol L-1; [MBA] = 0.138 mol L-1. Thereafter, the optimised molar ratio of AAm AA, AAm AN, and AAm MAA, keeping AAm as the principal monomer, were (0.071+0.037) mol L-1, (0.071+ 0.040) mol L-1, and (0.071+0.051) mol L-1respectively. Synthesised hydrogels were characterised by FT-IR, SEM, XRD, and TGA/DTA/DTG. The swelling capacity of hydrogels was investigated in deionised water. Moreover, the effect of the ionic strength of various cations (Na+, Ba+2, Fe+3, and Sn+4) and cationic charge on the swelling capacity of the hydrogels in different salt solutions was also studied, and the percentage swelling was found to decrease with increased ionic strength and cationic charge.

A functional NPSR1 gene variant and environment shape personality and impulsive action: A longitudinal study

Neuropeptide S and its receptor NPSR1 are involved in the regulation of arousal, attention and anxiety. We examined whether the NPSR1 gene functional polymorphism Asn¹⁰⁷Ile (rs324981, A>T) influences personality, impulsivity, and attention-deficit/hyperactivity disorder (ADHD)-related symptoms in a population-representative sample, and whether any eventual associations depend on age, sex, family relations and stressful life events (SLE). We used self-reports or teachers' ratings for both the younger (n=593) and older (n=583) cohort of the longitudinal Estonian Children Personality, Behaviour and Health Study. Males with the TT genotype displayed more ADHD-related symptoms. Adaptive impulsivity and Extraversion increased the most from age 18 to 25. While highest increases were observed in AA men, TT women exhibited the largest decreases. For participants with the AA genotype, Warmth in family was inversely associated with Neuroticism, and positively associated with Extraversion and Adaptive impulsivity. High exposure to SLE increased impulsivity and ADHD scores in TT genotype subjects. We conclude that the NPSR1 A/T polymorphism is associated with impulsivity, ADHD symptoms and personality, mirroring the activity- and anxiety-mediating role of NPSR1. Heterozygous individuals were the least sensitive to environmental factors, whereas subjects with the AA genotype and TT genotype reacted to different types of environmental adversities.

Racial Disparities in CRP and ESR Levels in Inflammatory Bowel Disease

Purpose: Inflammatory markers, such as C reactive protein (CRP) and erythrocye sedimentation rate (ESR), are often utilized as adjuvant tools in monitoring activity and response in Inflammatory Bowel Disease. Prior studies have strongly linked CRP elevation and Crohn's Disease (CD), less so Ulcerative Colitis (UC), however relatively little is known about racial differences. We analyzed the ESR and CRP results in an African American and Hispanic population with IBD. Methods: We reviewed the charts of IBD patients followed in our clinic and identified 21 UC patients, of which 13 were AA and 8 Hispanic, and 14 with CD, 10 AA and 4 Hispanic, who had simultaneous ESR and CRP measurements. We plotted a scatter gram and calculated the R2 for the 2nd order polynomial regression of the two tests, to evaluate the correlation of CRP and ESR elevation. The patients were further classified descriptively into four quadrants created by arbitrary break points on the scatter gram (ESR=60, CRP=20). They were high ESR (h-ESR), low ESR (l-ESR), high CRP (h-CRP) and low CRP (l-CRP). Results: The calculated coefficient of determination revealed higher covariance of ESR and CRP in UC than CD. In each group the coefficient of determination was higher for AAs than for Hispanics (R2: UC-AA= 0.71, UC-HISP= 0.48, CD-AA= 0.33, and CD-HISP=0.00). In the h-ESR/h-CRP group there were 4 UCs and 1 CD. Four of these were AA and 1 was Hispanic. In the h-ESR/l-CRP group there were 5 UCs and 1 CD. Five patients were AA and 1 was Hispanic. In the l-ESR/h-CRP group 2 had UC and 4 had CD. Three were AA and 4 were Hispanic. In the l-ESR/l-CRP group 10 had UC and 6 had CD. 10 were AA and 6 were Hispanic. Of the 14 CD patients with active disease, one AA man had normal ESR and CRP, while 11 patients had CRP levels significantly more elevated than simultaneous ESR level. In the UC group, of the 8 Hispanics with active UC, 2/8 had normal ESR and CRP and another 5 had comparatively higher CRP than ESR levels. Conclusion: In our small cohort of African Americans and Hispanics with IBD, ESR and CRP were more likely to covary in UC rather than CD, in which ESR was seldom elevated (only 2/14 patients). African Americans with UC had significantly higher ESR levels than Hispanics, who tended to have lower ESRs with CRP elevations. Our data confirms the preferential elevation of CRP over ESR in CD in African Americans and Hispanics and suggests racial differences in inflammatory marker patterns in IBD which may help tailor diagnosis and care.

A Rare Case of Colorectal Peripheral T-Cell Lymphoma Associated with Mycosis Fungoides

Purpose: ‘Mycosis Fungoides' (MF) is an indolent T cell lymphoma, involving primarily skin with rare extracutaneous, or visceral involvement occurring in advanced stages of the disease. Gastrointestinal system involvement is very rare and it is associated with significant morbidity and mortality secondary to various complications. We are describing a case of “Peripheral T-Cell Lymphoma” involving the rectum and the colon diagnosed on a screening colonoscopy in a patient with a history of Mycosis Fungoides. A 66-year-old AA man with h/o of HTN, dyslipidemia, and mycosis fungoides was referred by his dermatologist for a screening colonoscopy. He denied any symptoms including weight loss, rectal bleeding, melena, hematemesis or altered bowel movements. His physical exam was notable for diffuse hypopigmented and hyperpigmented patches over the skin, primarily hands and feet. There was no evidence of splenomegaly or lymphadenopathy. He was lost to follow up for five years after a decade of stable disease. He was started on clobetasol topical ointment and narrow band UVB therapy. Colonoscopy showed a large ulcerated mass with greenish black exudate occupying 50-74% of the circumference of the rectum, extending 5cm from entry site up to 17cm. The biopsy showed colonic mucosa diffusely infiltrated by large atypical lymphoid cells with varied size, hyperchromatic nuclei and small nucleoli. Flow cytometry showed abnormal clonal T cell proliferation and stained positive for CD3, CD4, CD5 and rarely for CD8 suggestive of peripheral T cell lymphoma. A molecular study for TCR Gamma rearrangement performed on the previous lymph node biopsy and the current rectal specimen showed identical clonal peaks indicating that the process in the rectum likely represents transformation of the patient's cutaneous T cell lymphoma. A month later, he was admitted to the hospital with severe pain and swelling in his right lower extremity. He was found to be having a diffuse systemic involvement of T cell lymphoma of plural fluid, right thigh, inguinal lymphnodes, and CNS. His prognosis was assessed to be very poor and he was sent to hospice care based on his wishes for comfort care.Figure: No Caption available.

The prevalence of lower urinary tract symptoms (LUTS) and overactive bladder (OAB) by racial/ethnic group and age: Results from OAB‐POLL

To estimate the prevalence of LUTS and OAB in a large, ethnically diverse US study. This cross-sectional, population-representative survey was conducted via the Internet in the US among 10,000 men and women aged 18-70 (2,000 African-Americans [AA], 2,000 Hispanics, 6,000 whites). The LUTS tool assessed how often participants experienced LUTS during the past 4 weeks on a five-point Likert scale. OAB was defined by the presence of urinary urgency ≥ "sometimes" or ≥ "often," and/or the presence of urgency urinary incontinence (UUI). Descriptive statistics were used to evaluate group differences. Logistic regression analyses were conducted to examine the impact of racial/ethnic group on OAB. Response rate, 56.7%. Prevalent LUTS included terminal dribble and nocturia across gender, post-micturition leaking (men), and stress incontinence (women). Prevalence of OAB ≥ "sometimes" and ≥ "often" were 17% and 8% in men and 30% and 20% in women--with significantly higher rates among AA men and women. A similar trend was found for UUI among men (AA, 10%; Hispanic and whites, 6%), while AA and white women had higher prevalence of UUI (19%) as compared to Hispanic women (16%). In logistic regression analyses, AA and Hispanic men and women were significantly more likely than whites to have OAB despite having lower prevalence of self-reported comorbid conditions and risk factors. LUTS and OAB are highly prevalent in both men and women and increase with advancing age. Further, racial/ethnic group is a robust predictor of OAB in men and women.

Abstract P030: Variations in Cardiovascular Risk Among Different Clinical Presentations of Metabolic Syndrome in the REasons for Geographic And Racial Differences in Stroke (REGARDS) Study

Background: Some individuals classified as having metabolic syndrome (MetSyn) are centrally obese while others are not with unclear implications for cardiovascular (CV) risk. Methods: REGARDS is following 30,239 individuals ≥45 years of age living in 48 states recruited from 2003-7. MetSyn risk factors were defined using the AHA/NHLBI/IDF harmonized criteria with central obesity being defined as ≥88 cm in women and ≥102 cm in men. Participants with and without central obesity were stratified by whether they met &gt;2 or ≤2 of the other 4 MetSyn criteria, resulting in the creation of 4 groups. To ascertain CV events, participants are telephoned every 6 months with expert adjudication of potential events following national consensus recommendations and based on medical records, death certificates, and interviews with next-of-kin or proxies. Acute coronary heart disease (CHD) was defined as definite or probable myocardial infarction or acute CHD death. To determine the association between these 4 groups and incident acute CHD, we constructed Cox proportional hazards models in those free of CHD at baseline by race/gender group, adjusting for sociodemographic variables. Results: A total of 20,018 individuals with complete data on MetSyn components were free of baseline CHD. Mean age was 64+/−9 years, 58% were women, and 42% were African American. Over a mean follow-up of 3.4 (maximum 5.9) years, there were 442 acute CHD events. In the non-centrally obese with&gt;2 other risk factors, risk for CHD was higher for all but AA men, though significant only for white men. In contrast, in the centrally obese with &gt;2 other risk factors, risk was doubled for women, but only non-significantly and modestly increased for men. Only AA women with central obesity and ≤2 other risk factors had increased CHD risk (Table). Conclusion: The CHD risk associated with the MetSyn varies by the presence of central obesity as well as the race and gender of the individual.

Y chromosome lineages in men of west African descent.

The early African experience in the Americas is marked by the transatlantic slave trade from ∼1619 to 1850 and the rise of the plantation system. The origins of enslaved Africans were largely dependent on European preferences as well as the availability of potential laborers within Africa. Rice production was a key industry of many colonial South Carolina low country plantations. Accordingly, rice plantations owners within South Carolina often requested enslaved Africans from the so-called “Grain Coast” of western Africa (Senegal to Sierra Leone). Studies on the African origins of the enslaved within other regions of the Americas have been limited. To address the issue of origins of people of African descent within the Americas and understand more about the genetic heterogeneity present within Africa and the African Diaspora, we typed Y chromosome specific markers in 1,319 men consisting of 508 west and central Africans (from 12 populations), 188 Caribbeans (from 2 islands), 532 African Americans (AAs from Washington, DC and Columbia, SC), and 91 European Americans. Principal component and admixture analyses provide support for significant Grain Coast ancestry among African American men in South Carolina. AA men from DC and the Caribbean showed a closer affinity to populations from the Bight of Biafra. Furthermore, 30–40% of the paternal lineages in African descent populations in the Americas are of European ancestry. Diverse west African ancestries and sex-biased gene flow from EAs has contributed greatly to the genetic heterogeneity of African populations throughout the Americas and has significant implications for gene mapping efforts in these populations.

Intake of Grains and Dietary Fiber and Prostate Cancer Aggressiveness by Race

Purpose. To examine the associations among intake of refined grains, whole grains and dietary fiber and aggressiveness of prostate cancer in African Americans (AA, n = 930) and European Americans (EA, n = 993) in a population-based, case-only study (The North Carolina-Louisiana Prostate Cancer Project, PCaP). Methods. Prostate cancer aggressiveness was categorized as high, intermediate or low based on Gleason grade, PSA level and clinical stage. Dietary intake was assessed utilizing the NCI Diet History Questionnaire. Logistic regression (comparing high to intermediate/low aggressive cancers) and polytomous regression with adjustment for potential confounders were used to determine odds of high prostate cancer aggressiveness with intake of refined grains, whole grains and dietary fiber from all sources. Results. An inverse association with aggressive prostate cancer was observed in the 2nd and 3rd tertiles of total fiber intake (OR = 0.70; 95% CI, 0.50–0.97 and OR = 0.61; 95% CI, 0.40–0.93, resp.) as compared to the lowest tertile of intake. In the race-stratified analyses, inverse associations were observed in the 3rd tertile of total fiber intake for EA (OR = 0.44; 95% CI, 0.23–0.87) and the 2nd tertile of intake for AA (OR = 0.57; 95% CI, 0.35–0.95). Conclusions. Dietary fiber intake was inversely associated with aggressive prostate cancer among both AA and EA men.

Impact of race on biochemical disease recurrence after prostate brachytherapy

Understanding racial differences in disease presentation and response to therapy is necessary for the effective treatment and control of prostate cancer. In this study, the authors examined the influence of race on biochemical disease-free survival (BDFS) among men who received prostate brachytherapy. In total, 2301 men were identified who had a minimum follow-up of 24 months and had received low-dose-rate brachytherapy for prostate cancer at the Mount Sinai Medical Center from June 1990 to October 2008. Patient factors, with specific emphasis on patient race, were analyzed with respect to freedom from biochemical failure (FFbF). Kaplan-Meier analyses, life-tables, and log-rank tests were used to identify variables that were predictive of 10-year FFbF. In this series, a total of 2268 patients included 81% Caucasians, 12% African Americans, 6% Hispanics, and 1% Asians. The 10-year actuarial FFbF rate was 70% for AA men and 84% for all others (P = .002). Between Caucasian men and AA men, the 10-year FFbF rate was 83% versus 70%, respectively (P = .001).There was no significant difference in 10-year FFbF between Caucasian men and Hispanic men (83% vs 86%, respectively; P = .6). The 10-year FFbF rate for Hispanic men and AA men was 86% versus 70%, respectively (P = .062). A greater percentage of AA men presented with higher prostate-specific antigen levels (PSA) (>10 ng/mL; 44% vs 21%; P < .001) and, thus, with higher risk disease (24% vs 15%; P < .001) compared with Caucasian men. Among the men with low-risk disease, the 10-year FFbF rate was 90% for Caucasian men and 76% for AA men (P = .041). The 10-year BDFS rate for patients who received brachytherapy alone was 86% for Caucasian men and 61% for AA men (P = .001); however, this difference was not observed when brachytherapy was combined with androgen-deprivation therapy(ADT) with or without supplemental external-beam radiotherapy (EBRT). Multivariate analysis revealed that PSA (P = .024), Gleason score (P < .001), the biologic effective dose (P < .001), EBRT (P = .002), ADT (P = .03), and AA race (P = .037) were significant predictors of 10-year FFbF. No significant differences was observed in overall survival, cause-specific survival, or distant metastasis-free survival between racial groups. AA race appeared to be an independent negative predictor of BDFS after prostate brachytherapy, and this result may highlight the need for more aggressive therapy in this patient population.

Abstract 1820: Genetic polymorphisms in microRNA target sites in IL-16 and IL-18 may be informative of time to prostate cancer diagnosis in African American men

Abstract Background: MicroRNAs (miRNAs) have recently been identified as promising markers to study for genetic susceptibility to cancer and have potential clinical utility in prostate cancer (PCA) risk assessment. Single nucleotide polymorphisms (SNPs) in genes encoding miRNA target sites for mRNA may interfere with miRNA binding to the mRNA, leading to aberrant mRNA expression and carcinogenesis. Here, we studied SNPs in 4 genes (ALOX15, IL-16, IL-18, and RAF1) with biologic relevance to PCA that encode mRNA with miRNA target sites. We evaluated these SNPs for association to race and time to PCA diagnosis in men at high risk for PCA (men with a family history [FH] of PCA and African American [AA] men) enrolled in a prospective early detection program to determine their future role in personalizing PCA early detection. Methods: The Prostate Cancer Risk Assessment Program (PRAP) is a prospective screening program for high risk men. PRAP has &amp;gt; 800 participants, and 60% are AA. Average follow-up is 4 years. Eligibility for PRAP includes men ages 35-69 years with one first degree relative with PCA, two second degree relatives with PCA on the same side of the family, any AA man regardless of FH of PCA, and men with BRCA1/2 mutations. Criteria for biopsy and biopsy approach have been reported previously. Genotyping methods included either Taqman® SNP Genotyping Assay (Applied Biosystems) or pyrosequencing. Standard sequencing was performed on 2% of the samples to confirm genotype calls. Standard statistical methods were used to determine risk-genotype distributions. Cox models were used for time to PCA diagnosis by risk genotype. Results: SNP genotypes were available for the following: n=749 for ALOX15, n=754 for RAF1, n=753 for IL-16, and n=766 for IL-18. There was a significant difference in distribution of miRNA target SNPs by race in ALOX15 (p&amp;lt;0.0001), RAF1 (p&amp;lt;0.0001), and IL-18 (p&amp;lt;0.0001). Among 278 AA men with &amp;gt; one follow-up visit, the TT genotype at rs1131445 in IL-16 was found to be significantly associated with earlier time to PCA diagnosis vs. the CC/CT genotypes (p=0.013). Hazard ratio after controlling for age and PSA for TT vs. CC/CT among AA men was 2.27 (p=0.0091). In addition, among 283 AA men with &amp;gt; one follow-up visit, the TT genotype at rs360727 in IL-18 was found to predict earlier time to PCA diagnosis vs CC/CT (p=0.017). Hazard ratio for PCA after controlling for age and PSA for TT vs. CC/CT among AA men was 4.44 (p=0.042). No trends in time to PCA diagnosis were seen among Caucasian men in PRAP for any of the miRNA target SNP genotypes. Conclusions: Genetic polymorphisms in miRNA target sites in IL-16 and IL-18 may be informative of time to PCA diagnosis among AA men enrolled in PCA risk assessment and may help to tailor screening and prevention recommendations in the future. Further study among high-risk men is warranted. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1820. doi:10.1158/1538-7445.AM2011-1820

Abstract B56: Prostate cancer: A health disparity among African American men and the racial differences within nonmalignant prostate tissue pertaining to the differential expression of hZIPI.

Abstract African American men (AA) men suffer far worse from health related issues than any other racial group in America. In today's society, AA men are subjected to a lack of affordable health services, cultural barriers, poverty, employment that doesn't carry health insurance and insufficient medical and social services catering for black men. In nearly 50% of death certificates of prostate cancer (PC) patients, a condition other than PC is listed as the underlying cause of death. PC is the most frequently occurring cancer among men in the US, and is the second leading cause of cancer death. In general, the likelihood of dying of a condition other than from prostate cancer increases with the increase in age at diagnosis. In the United States, men of AA heritage have the highest incidence rate of PC but at a much earlier age than EAs. AA men are twice as likely to develop prostate cancer as well as have a 40% higher death rate from all other cancers or diseases combined. Heart disease is the number one worldwide killer of both men and women in the United States, where it is responsible for 40% of all deaths. We speculate that there is an underlying molecular link found between the development of PC and cardiovascular disease in relation to the mortality rate of AA men. Although the mortality rate of PC is high but currently declining, there still remain an underestimated number of deaths associated with the disease. The content of zinc in the prostate glandular cells is among the highest in the body, serving as an essential trace element responsible for key biological processes. Zinc is essential for a very large number and variety of cellular functions but is also potentially toxic. Zinc homeostasis is therefore dynamically maintained by a variety of transporters and other proteins distributed in distinct cellular and subcellular compartments. The role of zinc, its underlying active function in the development and progression of prostate malignancy and its potential application are contemporary critical issues for the medical/ scientific community. We therefore theorize that the accumulation of zinc and its transportation, specifically hZip1, is down-regulated in the prostate gland of AAs at an earlier age compared to that of their EA counterpart. Through a series of experiments (in situ hybridization/PCR, RT-PCR, differential Zn staining, and X-ray fluorescent spectrometry) we were able to observe the accumulation of zinc and calibrate the expression of hZip1 to determine the differences between similar age groups of AA males and EA males in order to distinguish obscure differences within the stroma and glandular regions of the prostate. Common diseases, such as cancer and cardiovascular disease are a result of the complex interplay of genetic and environmental factors. Virtually all human diseases are the result of the interaction of genetic susceptibility factors and modifiable environmental factors, broadly defined to include infectious, chemical, nutritional and behavioral factors. In AA men, PC has often already advanced to the stage of metastasis when first detected. By providing evidence for reasons why AA men are more susceptible to developing earlier and in the case of aggressiveness, many can be detected and treated in the early stages of expansion and development. Citation Information: Cancer Epidemiol Biomarkers Prev 2010;19(10 Suppl):B56.

Abstract A37: Methodological considerations in comparing first-generation Jamaican black immigrants to U.S.-born black (African-American) men in public health, behavioral, or health disparities research

Abstract Introduction: The findings of the present study resulted from a larger study of African American and Jamaican culture-based attitudes and behaviors regarding prostate cancer and prostate cancer screening. The original study was designed to conduct an in-depth exploration of ethnicity and culture-related pathways by which psychosocial processes may influence prostate cancer knowledge, attitudes, and screening behaviors. To identify and describe the unique cultural norms that influence African American and African Caribbean (Jamaican) men's attitudes and cancer screening practices, we first had to determine if a clear distinction between African American and Jamaican cultures existed between the two black ethnic subgroups. This study describes the process and challenges whereby investigators identified the ethnic and cultural inclusion criteria by which black men would be categorized as African American or Jamaican as well as the exclusion criteria which would preclude men from participating in the larger study of black ethnicity, culture, and prostate cancer knowledge, attitudes, and screening behaviors. Methods: A qualitative research design was used to explore what it meant to be either AA/Black or Jamaican/Black. Investigators conducted face-to-face, semistructured, taped interviews with 36 self-identified AA men and 24 Jamaican black men residing in the southern U.S. The participant's open-ended responses of their perceptions of ethnicity and culture were analyzed using the constant comparative method. The results of the analyses were used to assign study participants to either AA or Jamaican ethnocultural categories. Results: The results of the in-person interviews and analyses revealed qualitative distinctions between AA men born in the U.S. to at least two generations of U.S.-born black parents and first generation Jamaican-born men who resided in the country of Jamaica until at least age 12 and immigrated to the U.S. thereafter. In addition, a subsample of black men who self-identified as Jamaican were able to describe their ability to move effortlessly between the AA and Jamaican cultures depending on the social and political circumstances (these Jamaicans migrated to the U.S. prior to age 12). By contrast, AA men born and residing in the southeastern U.S. did not describe the ability to move in and out of Jamaican cultures. Conclusion: As a result, we concluded that in order to draw clear distinctions between AA and Jamaican cultures, the Jamaican men in our study population would be defined as first-generation Jamaican immigrants to the U.S. who resided in the country of Jamaica until at least age 12. AA men would be U.S.-born to at least two generations of U.S. born black parents and have lived in the U.S. with the exception of military service. Citation Information: Cancer Epidemiol Biomarkers Prev 2010;19(10 Suppl):A37.

Cystic Artery Pseudoaneurysm: A Rare Cause of Massive GI Bleed

Purpose: A 33-yr-old AA man presented to the EC with nausea and vomiting blood clots that started 12 hrs prior. He had a medical history of HIV and choledocholithiasis for which he had an ERCP with sphincterotomy and laparoscopic cholecystectomy two months prior to admission. His hemoglobin was 5.9 g/dl on arrival. He had significant right upper quadrant abdominal pain. He was admitted to the medical ICU and the GI service was consulted. An initial EGD revealed no source of bleeding, there was blood in the second portion of the duodenum but no active bleeding from the previous sphincterotomy. An ERCP was planned, however, prior to the procedure the patient had massive hematemesis and became hemodynamically unstable necessitating an emergent mesenteric angiography in interventional radiology. Superior mesenteric, inferior mesenteric and celiac axis arteriograms were performed and showed gross extravasation at the region of the stump of the cystic artery. This was successfully embolized and a subsequent angiogram showed no more extravasation. He had no more episodes of bleeding and he was discharged home. Cystic artery pseudoaneurysm which develops following a cholecystectomy and resulting in upper gastrointestinal bleeding is a rare entity, with only four cases described in the literature. The symptoms may appear in the early postoperative period or as late as 120 days after surgery. Among the possible causes is the excessive use of electrocautery during the dissection at the infundibulum of the gallbladder, causing thermal injury to the vascular wall, and erosion of the inner wall of the cystic artery caused by contact with the tip of the metal clip used to occlude the cystic duct. The classical triad of upper gastrointestinal bleeding, pain in the right upper quadrant and obstructive jaundice described by Quincke is present in about a third of the patients. Even though our patient demonstrated gross extravasation of contrast, the presence of a dilated cystic artery stump on angiogram following cholecystectomy is an “ominous sign”, even in the absence of active extravasation of contrast. We present this case of a massive gastrointestinal bleed to highlight the rare entity of cystic artery pseudoaneurysm. Explicit knowledge of the patients past surgical history and a high index of suspicion are needed to successfully diagnose and treat this often life threatening condition. An initial endoscopic evaluation is warranted and if no source is identified than selective arteriography followed then by embolization is the next modality of choice. High index of suspicion and swift transition from endoscopy to angiography has been shown to reduce mortality and morbidity as demonstrated by our case.

Coronary Heart Disease Risk Prediction in the Era of Genome-Wide Association Studies

For DNA-based tests that assess genetic predisposition to coronary heart disease (CHD) to be of clinical value, they need to provide information over and above conventional risk factors (CRFs) currently used in risk algorithms, such as the Framingham Risk Score,1 which incorporates CRFs such as age, gender, blood lipid concentrations, blood pressure, body mass index, family history, and smoking habit. To achieve this, several hurdles must be passed. The first challenge is to identify a set of common single-nucleotide polymorphisms (SNPs) at loci associated with CHD risk. Over the last 10 to 15 years, this has been done by use of a “candidate gene” approach through association studies in prospective analysis or case-control studies, ie, comparing SNP genotype or allele frequency between groups of individuals with CHD and healthy subjects. Several of the genes, chosen because of their key role in processes that predispose to atherosclerosis, have meta-analysis–confirmed effects on risk of CHD,2 the best example of which is the APOE gene, which encodes apolipoprotein E, with 3 common isoforms that are associated with strong effects on plasma lipids and more modest effects on risk of CHD.3 This “hypothesis-driven” search for useful genetic variants provides the foundation for the development of genetic CHD risk profiles, and in the last 2 years, it has been enhanced by technical advances that have allowed “hypothesis-free” genome-wide association studies (GWASs), primarily in a case-control setting. Although the list of identified CHD-risk loci and SNPs will clearly grow, we have at least the basis to start the examination of their potential clinical utility. The second set of challenges is to obtain a robust estimate of the size of the risk effects associated with these SNPs. This requires population-based prospective studies to avoid bias, because estimates in the case-control setting, although efficient for …

Abstract 2712: Heterogeneous nuclear ribonucleoprotein H1 confers transcription and transactivation of androgen receptor: Implications for prostate cancer progression in African American men

Abstract Caucasian American (CA) and other ethnic minority groups. The causes of this ethnic disparity in clinical manifestation and outcome of the disease are not well understood. Here we identified, by employing a combined approach of laser capture microdissected (LCM), suppressive subtractive hybridization (SSH), and custom race-based CaP cDNA microarray on fresh specimens, selective expression of heterogeneous nuclear ribonucleoprotein H1 (hnRNPH1) in prostate tumor cells of AA men in comparison to CA men. An ethnicity-based tissue microarray (TMA) analysis revealed selective nuclear accumulation of hnRNPH1 in tumor cells compared to adjacent normal epithelium and benign prostatic hyperplasia (BPH). We also show that hnRNPH1 up-regulates transcription, physically interact with, and confers hormone-dependent (HD) and independent (HI) transactivation of androgen receptor (AR) in CaP cells. Further, our reporter, ChIP, and EMSA analyses demonstrate hnRNPH1 binds to androgen response elements (AREs) on promoter and enhancer element of PSA gene and the ligand binding domain-encoding exons D, E and H of the AR gene, suggesting it acts as a coactivator of AR in CaP cells. Interestingly, siRNA silencing of hnRNPH1caused growth arrest and enhanced cytotoxicty of Bicalutamide in AR-expressing CaP cells. These findings support a model in which hnRNP H1 is an exclusive auxiliary factor for AR to elicit androgen-specific transcriptional regulation of androgen-regulated genes and drug resistance. Given heterogeneity of CaP and that AR is implicated in androgen independent progression of CaP, the results demonstrate a previously uncharacterized mechanism for AR-hnRNPH1 axis in disease progression and hormone refractory via enhancing HD and HI mediated transcription and transactivation of AR in a subset of prostate tumor cells in AA men. The results not only reveal racial differences in the biology of CaP, but also provide, for the first time, a new frontier for the development of diagnostic, preventive, and/or targeted therapeutic strategies to circumvent disease progression in AA men. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2712.

Cardiovascular Disease Control Through Barbershops: Design of a Nationwide Outreach Program

To review the success of barbershops as vehicles for health promotion and outline the Black Barbershop Health Outreach Program (BBHOP), a rapidly growing, replicable model for health promotion through barbershops. BBHOP was established by clinicians in order to enhance community level awareness of and empowerment for cardiometabolic disorders such as diabetes and cardiovascular disease. At coordinated events utilizing existing infrastructures as well as culturally and gender-specific health promotion, BBHOP volunteers screen for diabetes and hypertension and reinforce lifestyle recommendations for the prevention of cardiometabolic disorders from the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Patrons with abnormal findings are referred to participating physicians or health care facilities. We performed a selective review of the literature in order to place this model for health promotion in the context of previous efforts in barbershops. BBHOP is among several successful programs that have sought to promote health in barbershops. Combining a grassroots organization approach to establishing a broad-based network of volunteers and partner agencies with substantial marketing expertise and media literacy, the BBHOP has screened more than 7000 African American men in nearly 300 barbershops from more than 20 cities across 6 states. The BBHOP is an effective method for community level health promotion and referral for cardio-metabolic diseases, especially for AA men, one of the nation's most vulnerable populations.