The racial pandemic experienced by Black American men: Cognitive-behavioral and structural implications.

Background: Disparities in prostate cancer (PrCa) incidence and mortality between African American (AA) and European American (EA) men are partially mediated by underlying disease biology. The goal of this study was to determine how DNA methylation and transcriptomic changes drive PrCa health disparities in AA men. Methods: Transcriptomic alterations potentially mediated by DNA methylation were identified by Illumina arrays and RNA-sequencing in PrCa from 30 AA and 32 EA men. Androgen receptor (AR) protein expression was measured using tissues microarray of matched PrCa tissues from 95 EA and 92 AA men. In vitro, MDA PCa 2a (2a)/MDA PCa 2b (2b) cells derived from an AA man and LNCaP/LaPC-4 cells derived from EA men were stimulated with ionomycin, a calcium ionophore to measure intracellular calcium using fluorescent-based live imaging. Results: Unsupervised hierarchical clustering revealed DNA methylation clusters (Cluster A and Cluster B) with differential methylation of loci that regulate intracellular calcium levels including RYR2, TRPC6, and TRPA1. Increased methylation of calcium regulatory genes in Cluster A was associated with reduced disease-free time (DFT) (21.65 vs 46.71 months, p<0.05) only in AA men with PrCa. RYR2 (-0.122 vs -0.004, p=0.69), TRPC6 (0.006 vs -0.639, p=0.06) and TRPA1 (-0.070 vs -0.269, p<0.05) transcript levels were lower in Cluster A compared to Cluster B. These data suggest DNA methylation can regulate expression of calcium regulating genes. In vitro, we found AA PrCa derived 2b cells have reduced RNA levels of RYR2, TRPV6 and CALB1 compared to EA PrCa derived LNCaP cells. Reduced transcription can result in lower protein expression and thus activity of calcium regulatory genes. To test this, we stimulated cells with ionomycin and found a rapid increase in intracellular calcium in 2a/2b cells (within 60 seconds) compared to LNCaP/LAPC-4 cells (120-300 seconds). This suggests that decreased transcription correlates to reduced buffering capacity of calcium regulatory genes. Others have shown that increased intracellular calcium reduces AR protein levels. Therefore, we analyzed AR protein expression in a subset of tumors from Cluster A and B. AR levels were lower in adjacent non-tumor and tumor tissue in these overlapping samples. AR low PrCa are associated with basal like features and respond poorly to androgen deprivation therapy. Therefore, we analyzed the PAM50 basal/luminal gene sets and AR target genes and found differentially expression of these genes in AA PrCa derived 2b and EA PrCa derived LNCaP cells. Conclusions: Our study shows that AA men with PrCa have epigenetically dysregulated calcium signaling that is associated with worse DFT. Our ongoing work seeks to identify how these alterations regulate AR expression and thus basal/luminal features. Our long- term goal is to establish novel molecular subtypes using calcium-AR-basal/luminal features that can guide design of rationale therapies in a subset of AA men with PrCa. Citation Format: Swathi Ramakrishnan, Xuan Peng, Eduardo C. Gomez, Kristopher Attwood, Ivan V. Maly, Wilma A. Hoffmann, Wendy Huss, Gissou Azabdaftari, Li Yan, Jianmin Wang, Anna Woloszynska. Intracellular calcium regulates androgen receptor expression and basal-luminal features in prostate cancer from African American men [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-134.

Background: Secondary to their comparable racial and socio-demographic background, African American (AA) men and women with breast cancer are expected to have similar outcomes. However, there is a paucity of data demonstrating gender-specific differences in breast cancer across racial/ethnic groups. Our objective is to investigate potential differences between AA men, AA women and White men with breast cancer by evaluating risk factors using a population-based tumor registry. Methods: A retrospective review of the Surveillance Epidemiology and End Results (SEER) database from 1988 to 2008 was conducted. We identified AA men and AA women aged 20 years or older with a primary breast cancer diagnosis or in whom the index breast cancer is the first cancer. A similar group of White men were included to serve for comparison. All available treatment modalities were reviewed. Bivariate analysis of patient characteristics, tumor grade, stage, hormonal assay, and treatment modality was performed using Chi squared test. Survival was estimated and Cox proportional model was used to investigate survival differences comparing AA men, AA women and White men (with AA men as reference), adjusting for age, year of diagnosis, tumor characteristics, as well as treatment received. Subset analyses were done within stage strata. Results: We reviewed 62 758 patient records comprising 506 (0.81%) AA male, 59 234 (94.38%) AA female and 3 018 (4.81%) White males. Most were 50 years or older (57.5%), married (39.4%), had invasive ductal carcinoma (61.9%) and localized disease (42.5%). Mean age at diagnosis was 59 (±11), 55 (±12) and 63 (±11) years for AA males, AA females and White males, respectively. Men were more likely to have moderately differentiated tumors (37.6% and 40.4% for AA males and White males, respectively) compared to AA women who were more likely to have poorly differentiated tumors (39.2%) (p<.001). AA males had more regional disease (39.5%) compared to AA females and White males who had more localized disease (42.6% and 41.5%, respectively). Incidence of distant metastasis was highest among AA men (10.9%) compared to their AA female (6.10%) and White male (5.8%) counterparts (p<.001). Men received more modified radical mastectomies (61.2% and 62.6% for AAs and Whites, respectively) and women had more partial mastectomies (56.4%). The 5- and 10-year survival was 78% (95% CI .73-.82) and 66% (95% CI .59-.72) for AA men, 80% (95% CI .80-.81) and 73% (95% CI .72-.73) for AA women, 88% (95% CI .86-.89) and 79% (95% CI .77-.81) for White men. Overall, White men were 24% less likely to die from breast cancer compared to AA men (HR 0.76; 95% CI .62-0.94), while the survival difference was not significant when compared to AA women (HR: 0.98; 95% CI: 0.81-1.19). Similarly, among patients with regional disease, White men had significantly better survival (HR: 0.63; 95% CI: 0.46-0.48) compared to AA men. Conclusion: Using a large population-based database, our study demonstrates absence of gender specific difference in breast cancer survival among African Americans. However, AA men were found to have larger tumors, worse stage, and despite presenting with similar grade and receiving similar treatment as White males, had worse outcome. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-12-05.

The recently published article by Tang et al,1 who investigated treatment choices among men with prostate cancer (PCa) presenting at a multidisciplinary (MultiD) clinic in comparison with nationwide trends (from the Surveillance, Epidemiology, and End Results [SEER] database), was of great interest to us. Their results revealed similar treatment trends in the MultiD clinic and SEER cohorts, whereas definitive treatment decreased with age, later diagnosis, and low-risk disease. They found differences in the high-risk patient cohorts, where MultiD patients were more likely to undergo definitive treatment than SEER patients. However, the result that was of most interest to us involved the differences in treatment choices among African American men within the 2 cohorts. We hope to further discuss these interesting results and its future implications with the authors and the readers of Cancer. In the MultiD clinics, being an African American man was associated with increased use of definitive therapy in comparison with white men (odds ratio [OR] for brachytherapy, 1.17; OR for external-beam radiation therapy, 1.41; OR for prostatectomy, 1.52; all P values <.01). This finding was consistent in the SEER cohort, where being an African American male was associated with increased use of definitive therapy, although the magnitude of association was less. Within the MultiD cohort, older African American men with low-risk disease opted for nondefinitive therapy at a significantly higher rate than white men. This difference was not seen within the SEER cohort, where African American and white patients were treated with nondefinitive therapy at approximately equal frequencies across all age groups. The intermediate- and high-risk African American groups in the MultiD clinic received definitive therapy more often than their white counterparts, and this was in contrast to the SEER cohort, in which intermediate- and high-risk African Americans received definitive therapy less often than the white patients. First, it is important to note that the racial differences in PCa mortality are among some of the most severe in all of oncology.2 African American men have been found to present at a younger age with more aggressive cancer and to have higher mortality from PCa in comparison with white men.3 In addition, factors such as ineffective patient-provider communication4 and increased medical mistrust5 are cited more frequently by African American patients and are known to affect treatment adherence, choices, and ultimately outcomes.6 In an unpublished analysis of our institutional database, we found that biopsy-naive white men were more likely to undergo magnetic resonance imaging–ultrasound fusion biopsy for the initial PCa evaluation in comparison with African American men, who were more likely to undergo 12-core systematic biopsy alone; this provided evidence that the racial disparities in PCa extend into the initial biopsy method used for cancer detection. This is where the advent of MultiD clinics, which aim to provide more comprehensive, individualized treatment options as well as an increase in shared decision making between patient and provider, may have utility in improving outcomes for African American men with PCa. The use of MultiD clinics in the initial management of PCa leads to high patient satisfaction, improves patients' appreciation (because they feel better informed), promotes active participation and shared decision making, and strongly influences patients' final decision on treatment.7 MultiD prostate clinics have been found to lead to high rates of treatment decision alteration and increased adherence to National Comprehensive Cancer Network guidelines,8 as also seen in the study by Tang et al,1 in which older African American men with low-risk disease at their MultiD clinic opted for nondefinitive therapy at a higher rate and African American men with intermediate- and high-risk disease opted for definitive therapy at a higher rate in comparison with white counterparts from the SEER database. It is possible that the altered treatment choices by African American men in this study were due to a combination of patients being more involved in their own care, being more educated about their treatment options, and being more trusting of their providers as a result of the MultiD prostate clinic. To our knowledge, this is one of the first studies that provides evidence of MultiD clinics leading to altered treatment choices between African American and white men in PCa management in comparison with national trends. Because of the known racial differences in PCa, the growing number of treatment options available, and the increasing utilization of MultiD clinics for PCa management, we believe that this study may be the first of many future studies showing the utility of MultiD clinics in altering treatment choices among African American men and ultimately helping to decrease the racial disparities seen in PCa. No specific funding was disclosed. The authors made no disclosures.

Background: Men with a family history (FH) of prostate cancer (PCA) and African American (AA) men are at 2 to 7-fold increased risk for the disease. Assessing risk for PCA in these high-risk men has been challenging due to the lack of available genetic testing. The vitamin D and androgen pathways have been studied for years for association to prostate cancer risk with single nucleotide polymorphisms (SNPs) in the vitamin D receptor (VDR) gene and genes encoding enzymes involved in testosterone biosynthesis found to have no substantial association to prostate cancer risk. However, a recent study found an interaction between the FokI SNP in VDR and the V89L SNP in SRD5A2 (converts testosterone to dihydrotestosterone) in non-Hispanic white men. In addition, in Hispanic white men, the V89L SRD5A2 polymorphism and the CDX2 VDR SNP was associated with prostate cancer. We evaluated these particular genetic variants in VDR and SRD5A2 for association to prostate cancer and time to prostate cancer diagnosis in high-risk men enrolled in the Prostate Cancer Risk Assessment Program (PRAP)- a screening and research program with 60% African American participation. Methods: 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, or men with BRCA1/2 mutations. Current criteria for biopsy include PSA &amp;gt; 2.0 ng/mL, PSA 1.5–2.0 ng/mL with free PSA &amp;lt; 25%, any abnormality on digital rectal examination, or PSA velocity of 0.75 ng/mL/year. All biopsies are 12-core under transrectal ultrasound guidance with additional cores taken at physician discretion. Genotyping of SRD5A2 V89L and VDR CDX2 was performed using the Taqman® SNP Genotyping Assay (Applied Biosystems) per manufacturer's instructions. Pyrosequencing methods were used for the FokI SNP in VDR as Taqman assays did not produce reliable results. Standard statistical methods were used to determine allele and genotype distributions by race. Cox models were used to determine time to PCA diagnosis. Results: 661 PRAP men had genotype data available for FokI and V89L, while 380 men had genotype data for CDX2 and V89L. Among 236 AA men with at least one follow-up visit included in the FokI-V89L analysis, a significant interaction was seen between FokI and V89L genotypes after adjusting for age and PSA at entry (p=0.01). Hazard ratio estimates for AA men with the FokI CC genotype and V89L LV/LL genotypes vs. VV was 2.51 (95% CI 1.07–5.90). No interaction was seen between FokI and V89L genotypes among 194 Caucasian men, where FokI genotype alone was found to have a significant association to PCA (Hazard Ratio for FokI TT/CT vs CC = 0.29, 95% CI 0.14–0.62). No significant association to PCA was seen for CDX2 either alone or in combination with V89L for AA and Caucasian men in this analysis. Conclusions: FokI CC in VDR and V89L LV/LL in SRD5A2 appear to be informative of time to PCA diagnosis and risk for PCA in AA men undergoing PCA screening. FokI TT/CT genotype appears to have a protective effect in Caucasian men for PCA. Further study is warranted. Citation Information: Cancer Prev Res 2010;3(1 Suppl):A9.

African American men have the highest rates of prostate cancer incidence and mortality in the United States. Understanding underlying reasons for this disparity could identify preventive interventions important to African American men. To determine whether the association of obesity with prostate cancer risk differs between African American and non-Hispanic white men and whether obesity modifies the excess risk associated with African American race. Prospective study of 3398 African American and 22,673 non-Hispanic white men who participated in the Selenium and Vitamin E Cancer Prevention Trial (2001-2011) with present analyses completed in 2014. Total, low-grade (Gleason score <7), and high-grade (Gleason score ≥7) prostate cancer incidence. With a median (interquartile range) follow-up of 5.6 (1.8) years, there were 270, 148, and 88 cases of total, low-, and high-grade prostate cancers among African American men and a corresponding 1453, 898, and 441 cases in non-Hispanic white men, respectively. Although not associated with risk among non-Hispanic white men, BMI was positively associated with an increase in risk among African American men (BMI, <25 vs ≥35: hazard ratio [HR], 1.49 [95% CI, 0.95, 2.34]; P for trend = .03). Consequently, the risk associated with African American race increased from 28% (HR, 1.28 [95% CI, 0.91-1.80]) among men with BMI less than 25 to 103% (HR, 2.03 [95% CI, 1.38-2.98]) among African American men with BMI at least 35 (P for trend = .03). Body mass index was inversely associated with low-grade prostate cancer risk within non-Hispanic white men (BMI, <25 vs ≥35: HR, 0.80 [95% CI, 0.58-1.09]; P for trend = .02) but positively associated with risk within African American men (BMI, <25 vs ≥35: HR, 2.22 [95% CI, 1.17-4.21]; P for trend = .05). Body mass index was positively associated with risk of high-grade prostate cancer in both non-Hispanic white men (BMI, <25 vs ≥35: HR, 1.33 [95% CI, 0.90-1.97]; P for trend = .01) and African American men, although the increase may be larger within African American men, albeit the racial interaction was not statistically significant (BMI, <25 vs ≥35: HR, 1.81 [95% CI, 0.79-4.11]; P for trend = .02). Obesity is more strongly associated with increased prostate cancer risk among African American than non-Hispanic white men and reducing obesity among African American men could reduce the racial disparity in cancer incidence. Additional research is needed to elucidate the mechanisms underlying the differential effects of obesity in African American and non-Hispanic white men.

B54 Background Men with a family history (FH) of prostate cancer (PCA) and African American (AA) men are at 2 to 7-fold increased risk for the disease. Assessing risk for PCA in these high-risk men has been challenging due to the lack of available genetic testing. Recently, five genetic single nucleotide polymorphisms (SNPs) at chromosomal loci 8q and 17q (rs1859962, rs6983267, rs4430796, rs1447295, and rs16901979) were found to have a cumulative increased association with PCA in multiple studies. These genetic variants need to be characterized in screening populations to determine their utility in the early detection of PCA. The Prostate Cancer Risk Assessment Program (PRAP) at Fox Chase Cancer Center is a prospective screening program for high-risk men. Currently there are over 700 participants, and 60% are AA. This study evaluates the clinical characteristics of high-risk men carrying these risk SNPs and time to PCA diagnosis based on the presence of these 8q/17q risk markers. Methods 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. Current criteria for biopsy include PSA &amp;gt; 2.0 ng/mL, PSA 1.5-2.0 ng/mL with free PSA &amp;lt; 25%, any abnormality on digital rectal examination, or PSA velocity of 0.75 ng/mL/year. All biopsies are 12-core under transrectal ultrasound guidance with additional cores taken at physician discretion. Genotyping of SNPs rs1859962, rs6983267, rs4430796, and rs1447295 was performed using the Taqman® SNP Genotyping Assay (Applied Biosystems) per manufacturer’s instructions. Pyrosequencing methods were used for SNP rs16901979 as Taqman assays did not produce reliable results. Standard statistical methods were used to determine allele and genotype distributions by race. Cox models were used to determine time to PCA diagnosis by number of high risk SNPs. Results Genotypes for all five SNPs was able to be determined on 633 PRAP participants of whom 60% were AA. Average follow-up for these participants in PRAP has been 3-4 years. There was a statistically significant difference in the baseline distribution of risk alleles and risk genotypes of these five SNPs within self-reported race groups (p&amp;lt;0.0001). Age-adjusted baseline PSA differed significantly among high-risk Caucasian PRAP participants, with a higher baseline PSA in men carrying the risk genotype at rs4430796 vs. men without the risk genotype at this SNP (p=0.0063). More AA men were found to carry 2-3 and 4-5 risk-associated SNPs than high-risk Caucasian men in PRAP (p&amp;lt;0.0001). Time to PCA diagnosis was evaluated in 332 PRAP participants who had at least one follow-up visit. Among the 210 AA participants with at least one follow-up visit, there was a trend for earlier time to PCA diagnosis for those with 4-5 risk SNPs vs. 0-1 risk SNPs (p=0.059). Hazard ratios for PCA risk increased substantially in AA men with 4-5 SNPs vs. 2-3 SNPs (4.28 vs. 1.84), although this was not significant. No trends were observed for high-risk Caucasian men regarding time to PCA diagnosis. Conclusions Five genetic risk markers at 8q/17q may be useful in tailoring screening approaches in high-risk men, particularly AA men. Further follow-up is needed to firmly determine how these risk markers influence time to PCA diagnosis. Citation Information: Cancer Prev Res 2008;1(7 Suppl):B54.

Background: African American (AA) men have the highest mortality rate from prostate cancer compared to men from other races. Differences in the spectrum of somatic genomic alterations in tumors between AA men differs from non-AA men has not been well characterized as relatively few AA men have been included in prostate cancer genomic studies. To address this, we examined 5 publicly-available and commercial genomic datasets containing AA men with prostate cancer to identify novel alterations associated with race. Methods: In a meta-analysis of 4 public datasets, we investigated the mutational frequencies of 14 genes across 252 AA men and 635 non-AA men with primary prostate cancer. We also examined genomic alterations from the tumors of 436 AA men and 3018 EA men with primary or metastatic prostate cancer using the Foundation One assay. Results: We identified mutations in ZFHX3 and focal deletions in ETV3 more frequently in tumors from AA patients. The mutational frequency of TP53 was strongly associated with increasing Gleason grade. Using the commercial assay, we identified alterations in PTEN and TMPRSS2-ERG as less frequent in AA patients compared to non-AA patients in both primary and metastatic tumors. MYC amplifications were more frequent in AA patients with metastatic prostate cancer. Furthermore, we found that genomic alterations in KMT2D and CCND1 were more frequent in primary prostate tumors from AA patients, resulting in differential cell cycle genes and KMT alterations. MYC amplifications were more frequent in AA patients with metastatic prostate cancer. Genomic alterations in DNA repair genes were found at similar frequencies between EA and AA patients. Conclusion: While these results indicate that differences in mutational profiles may exist between racial groups in prostate cancers, additional sequencing studies that profile AA and EA men from the same clinical setting and that are matched for clinical covariates may be needed to confirm these findings. Overall, these results have implications for applying precision cancer medicine in AA prostate cancer patients. Citation Format: Yusuke Koga, Hanbing Song, Zachary Chalmers, Justin Newberg, Garrett Frampton, Joshua Campbell, Franklin Huang. Similarities and differences between genomic profiles of prostate cancers from African American and European American men with implications for precision cancer medicine [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr D120.

Introduction: African American (AA) men experience greater prostate cancer (PC) incidence and mortality compared to European American (EA) men, but the reasons are not fully understood. Some literature has identified connections between neighborhood disadvantage and aggressive PC, and AA men may be more likely to experience these factors than EA men. However, it is unclear if these associations may vary by race. We tested associations of two neighborhood disadvantage measures (neighborhood socioeconomic deprivation and racial segregation) with prostate tumor aggressiveness, overall and separately by race. We hypothesized that they would be positively associated and that associations would be stronger among AA men. Methods: We leveraged data from the University of Maryland Greenebaum Comprehensive Cancer Center Tumor Registry for AA and EA men who were diagnosed with PC from 2004-2021. We geocoded participants’ addresses at diagnosis to determine census tract-based Area Deprivation Index (ADI) and Racial Isolation Index (RI) values. ADI analyses included men diagnosed in 2005 or later (778 AA men and 687 EA men), and RI analyses included men diagnosed in 2009 or later (606 AA men and 454 EA men) based on data availability. We used logistic regression to model the odds of aggressive PC, defined as a Gleason pattern of 4+3 or a total Gleason score &amp;gt;=8, overall and by race. We fit models with scaled ADI or RI as the exposure variable, adjusting for race, age at diagnosis, and year of diagnosis. We also assessed an interaction between each neighborhood measure and race. Results: Median (interquartile range) ADI scores were 118 (101-137) for AA men and 92 (83-102) for EA men, and RI scores were 0.68 (0.35-0.87) for AA men and 0.11 (0.06-0.20) for EA men, indicating greater neighborhood deprivation and AA residential segregation among AA participants. The greatest values for these scores were concentrated in central and west Baltimore. A one-standard deviation (SD) increase in ADI was associated with significantly greater odds of aggressive tumors for AA men (OR=1.28, 95% CI: 1.10, 1.49; p&amp;lt;0.01), but not for EA men (OR=0.85, 95% CI: 0.67, 1.08; p=0.19), and the p-value for interaction (p&amp;lt;0.01) was statistically significant. Similarly, a one-SD increase in RI was significantly associated with aggressive tumors for AA men (OR=1.24, 95% CI: 1.03, 1.49; p=0.03), but not for EA men (OR=1.23, 95% CI: 0.84, 1.80; p=0.29), although the p-value for interaction was not statistically significant. Conclusions: Neighborhood disadvantage was significantly associated with higher odds of aggressive PC. The association of neighborhood deprivation and tumor aggressiveness was stronger among AA men. Additional analyses will consider other measures, including historical redlining, to further evaluate the relationship of neighborhood disadvantage with prostate tumor aggressiveness. Citation Format: Joseph Boyle, Jessica Yau, Jimmie L. Slade, Derrick A. Butts, Jessica Wimbush, Jong Y. Park, Arif Hussain, Eberechukwu Onukwugha, Cheryl L. Knott, David C. Wheeler, Kathryn Hughes Barry. Neighborhood disadvantage and prostate tumor aggressiveness among African American and European American men [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 809.

The status of African American boys and men is of significant concern. This article reviews the literature on African American males within the field of the psychology of men and masculinity. We focus on theory and research that describe African American men's masculinity, and how traditional masculinity and racial identity relate to the health and well-being of African American men. The article provides a context for introducing this special series of articles on African American men that advance our understanding of psychosocial factors associated with the health and well-being of African American men. Gibbs's classic 1988 book, Young, Black, and Male in America: An Endangered Species, brought much needed attention to the status of young African American males and suggested that there had been marked deterioration compared with past generations. Compared with earlier cohorts, young African American males were more likely to be unemployed, involved in the criminal justice system, unwed fathers, and victims of homicide and sui- cide. Almost 25 years later the status of African American boys and men continues to be an issue of significant concern. For example, African American men have the shortest life expectancy of all race/gender groups (National Center for Health Statistics, 2005). In 2006, the rate of new HIV infection for African American men was six times higher than European American men, nearly three times that of Hispanic/Latino men and twice that of African American women (Centers for Disease Control & Prevention, 2010). Further, African American men are six times more likely than European American men to be incarcerated (National Urban League, 2007). Lastly, the growth rate of African American men enrolling in college is the lowest among minority groups in the United States (Harvey, 2003). While these data are discouraging, other research has high- lighted strengths, progress, and psychosocial patterns character- ized by resilience. Compared with the national averages, African American men had lower rates of alcohol use and binge drinking from 2004-2008 (Substance Abuse & Mental Health Service Administration, 2010), and lower rates of mood disorders than both African American women and Whites (Breslau, Su, Kendler, Aguilar-Gaxiola, Kessler, 2005; Brown & Keith, 2003; Robins et

Introduction: African American men have the highest incidence and death rates from prostate cancer in the United States. The insulinlike growth factor (IGF) axis has been implicated in the carcinogenesis of prostate cancer. Several epidemiological studies have shown increased serum concentrations of IGF-1 and alterations of the associated binding proteins-IGFBP-2 and IGFBP-3, as strong risk factors for prostate cancer. This study examined racial differences in risk factors for prostate cancer in a healthy high risk screening population of African American and Caucasian males. The associations between IGF-1, IGFBP-2, IGFBP-3, prostate-specific antigen (PSA), testosterone, body mass index (BMI) and specific dietary macronutrients were examined. Methods: Serum was collected from 461 African American and Caucasian men aged ≥25 years who participated in prostate cancer screening programs located at two university hospitals in Washington, DC. Serum concentrations of IGF-1, IGFBP-2, IGFBP-3, PSA, and testosterone were analyzed using immunoassays from Diagnostic Systems Laboratories (Webster, TX). Height and weight were used to create BMI, which was calculated as weight/height2 (kg/m2). A food-frequency questionnaire was administered over the telephone to 128 study participants who consented. Wilcoxon rank sums test and chi square test examined mean differences and associations with other risk factors. Multiple linear regression analysis was used to examine racial differences in IGF-1, IGFBP-3, IGFBP-2, testosterone, PSA and specific macronutrients, adjusted for covariates such as age and BMI. Results: African American men had significantly lower concentrations of IGFBP-2 (p=0.035), and significantly higher concentrations of IGFBP-3 and testosterone when compared to Caucasian men, p=0.031 and p=0.033 respectively. There were no significant differences found for concentrations of IGF-1 by race. Levels of IGFBP-2 exhibited a significant inverse association with BMI for both races and a positive association with age for Caucasians. African American men had higher mean intakes of total calories, total fat, protein and carbohydrate, but only dietary fat intake was significantly higher when compared to intakes in Caucasian men (p=0.026). Multiple regression analysis revealed no significant relationships between nutrient intake and concentrations of IGF-1, IGFBP-3, IGFBP-2, PSA and testosterone by race. Finally, IGFBP-2 exhibited a significant univariate negative correlation with total calories, protein and total fat, with a somewhat stronger association among Caucasian than African American men. Conclusion: We provide evidence of racial variation in concentrations of IGFBP-2, IGFBP-3 and testosterone, but not for IGF-1. In this sample, African American men had a significantly higher consumption of total dietary fat intake than Caucasians. Further work is needed to determine whether these observations may explain the racial disparity in prostate cancer incidence and mortality in the U.S. Funded by: Department of Defense DAMD17-00-1-0024 Citation Information: Cancer Epidemiol Biomarkers Prev 2010;19(10 Suppl):A78.

INTRODUCTION: African American (AA) men experience greater prostate cancer incidence and mortality compared to European American (EA) men. Growing literature supports associations of neighborhood social factors (NSF) including neighborhood socioeconomic deprivation and residential segregation with advanced or aggressive prostate cancer, and AA men may experience these factors to a greater extent than EA men. Here we tested associations of NSF with prostate tumor RNA expression of stress-related genes, hypothesizing that these factors would be related and contribute to prostate tumor aggressiveness. METHODS: We leveraged available transcriptomic data from prostate tumor tissue for AA and EA men with prostate cancer who received radical prostatectomy surgery at the University of Maryland Medical Center. We geocoded each participant’s address at diagnosis, determined the corresponding census tract, and assigned tract-based Area Deprivation Index (ADI) and Racial Isolation Index (RI) scores to each participant. Based on data availability, ADI analyses included men diagnosed in 2005 or later (118 AA men and 43 EA men), and RI analyses included those diagnosed in 2009 or later (110 AA men and 37 EA men). We evaluated 105 stress-related genes, including those in the Conserved Transcriptional Response to Adversity, among others. We fit separate linear regression models for expression of each gene in relation to ADI or RI, respectively. Models were adjusted for race and age and year at surgery. We obtained q-values (p-values adjusted for multiple comparisons) using the Benjamini-Hochberg method. RESULTS: Median (interquartile range) ADI scores were 116 (101-131) for AA men and 91 (83-103) for EA men, and RI scores were 0.68 (0.38-0.87) for AA men and 0.10 (0.05-0.14) for EA men, indicating greater neighborhood deprivation and Black residential segregation among AA participants. The greatest values for these scores were concentrated in central and west Baltimore. ADI scores were positively and significantly (p&amp;lt;0.05) associated with expression for 11 genes. One gene, HTR6 (serotonin pathway), remained significant after multiple comparison adjustment (beta=0.0029, 95% confidence interval: 0.0014-0.0043; p&amp;lt;0.001; q=0.02). RI scores were positively and significantly associated with expression for 7 genes (p&amp;lt;0.05), but findings did not remain significant after multiple comparison adjustment. Four genes, including HTR6, IFIT2 and MX2 (roles in Type I IFN response), and IGLL1 (antibody synthesis) were significantly associated with both ADI and RI (p&amp;lt;0.05). Top findings among AA men only were similar to the overall results (AA and EA men combined). CONCLUSIONS: We identified several genes in stress-related pathways whose expression in prostate tumor tissue was higher among men with higher neighborhood deprivation or higher racial segregation. Additional analyses will consider other neighborhood measures, including historical redlining, to further investigate the role of NSF in prostate tumor RNA expression, tumor aggressiveness, and prostate cancer disparities. Citation Format: Joseph Boyle, Jessica Yau, Jimmie L. Slade, Derrick Butts, Yuji Zhang, Teklu B. Legesse, Ashley Cellini, Kimberly Clark, Jessica Wimbush, Nicholas Ambulos Jr., Jing Yin, Arif Hussain, Eberechukwu Onukwugha, Cheryl L. Knott, David C. Wheeler, Kathryn Hughes Barry. Neighborhood socioeconomic deprivation, racial segregation, and prostate tumor RNA expression of stress-related genes among African American and European American men [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr PR007.

In the United States, African American (AA) men are at 60% higher risk of developing prostate cancer than European American (EA) men, and AA men are 2.4 times more likely to die from prostate cancer than EA men. Although these disparities are frequently attributed to the greater aggressiveness of prostate cancer among AA men, it is not known what causes that prostate cancer aggressiveness in AA men. To identify germline genetic variation that could explain some of this disparity, our previous admixture mapping study identified a novel region on chromosome 7q31-34 where local ancestry was associated with risk of disease. The main objective of this study is to investigate whether candidate genes in this gene region show differences in protein product expression by cell line origin (AA vs. EA) and by cell line metastatic potential. We specifically examined the expression of three proteins sourced from this gene region through immunoblot analysis, filamin C (FLNC), glutamate receptor metabotropic B (GRM8), and cadherin-like and PC-esterase domain containing 1 (CPED1). The cell lines DU-145, PC3, LNCaP, RWPE1, and WPE1 were derived from biological specimens from EA men, whereas the PCa2b and the RC77T cell lines were sourced from AA men. The RWPE1 and WPE1 cell lines were derived from normal prostate cells, while the remaining cell lines were derived from metastatic prostate cancers. Using immunoblot analysis, we found that GRM8 is expressed at higher levels in the cell lines derived from AA men with prostate cancer compared to those from EA men with prostate cancer. In contrast, FLNC and CPED1 are expressed at higher levels in the cell lines from EA men with prostate cancer compared to those from AA men with prostate cancer. Interestingly, both FLNC and CPED1 expression is also low in the androgen sensitive LNCaP cell line. Importantly, these results are consistent with our fine mapping results in AA men, where the SNP with greatest evidence for association is located. Further, previous studies have demonstrated that the methylation status and mRNA expression of CPED1 and FLNC differed between prostate cancers from AA and EA men. Taken together, these results provide us with a foundation to test the relevance of these genes in prostate cancer growth and metastasis and contribute to our understanding of the molecular differences in prostate cancer between EA and AA men. Citation Format: Casey Wizner, Julie Ruterbusch, Nicole Kubinec, Gregory Dyson, Albert Levin, Julie Boerner, Cathryn Bock. Determination of protein expression of candidate prostate cancer genes from a novel region on chromosome 7 identified in African American men. [abstract]. In: Proceedings of the Ninth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2016 Sep 25-28; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(2 Suppl):Abstract nr B33.

Racial Disparities in Palliative Radiation for African American Men with Metastatic Prostate Cancer

Racial disparities in prostate cancer care: Is adherence to National Comprehensive Cancer Network guidelines good enough for our patients?

86 Background: Although ethnic differences in disease incidence among African American (AA) men may reflect differences in screening behaviors and behavioral and socioeconomic factors, genetic ancestry may be a factor. This study will investigate the association between West African and Native American genetic ancestry and PCa diagnosis. Methods: We enrolled 40-79 year-old men who were undergoing prostate biopsy or routine PSA screening at outpatient urology clinics in Chicago, IL. Blood was drawn at the time of enrollment for the genotyping of 105 ancestry informative markers. West African (WAA), European (EA), and Native American (NAA) genetic ancestry was estimated using the Bayesian Markov Chain-Monte Carlo method implemented in the program STRUCTURE. Univariate analysis was performed by Wilcoxon rank-sum test for continuous variables. Unconditional binary logistic regression models were used to estimate odds ratios for the likelihood of PCa diagnosis and for the odds of having high-risk PCa relative to controls, adjusting for age, body mass index (BMI), alcohol-use, and family history of PCa. Results: 857 men were enrolled; 34.5 % were diagnosed with PCa, 50.9 % were controls and 14.6 % were men with negative prostate biopsies. AAs comprised 27% of the sample. The median was 63 years (IQR 57 – 68). Among AA men, the median genetic WAA proportion was 0.78 (IQR 0.69 – 0.83) and NAA was 0.04 (IQR 0.02 – 0.09). There was no significant difference in genetic WAA among AA men with and without PCa diagnosis (p = 0.54); however, genetic NAA was significantly lower among PCa cases (median 0.034 vs 0.057,p = 0.03) compared to controls. Among EA men, the media NAA was 0.067 (IQR (0.03 – 0.10). Similarly among EA men, genetic NAA was significantly lower among cancer cases (0.04 vs. 0.08, p &lt; 0.001). On logistic regression, WAA ≥ 88% was associated with increased odds of PCa in AA men (OR 2.6 95% CI 1.1 – 6.7). In both AAs (OR 0.5, 95% CI 0.2 – 1.1) and EAs (OR 0.3, 95 % 0.2 – 0.6), men in the highest genetic NAA quintile had a decreased risk of PCa on logistic regression compared to men in the lowest quintile. Conclusions: Our study reveals that NAA is protective against PCa diagnosis among all men. Additionally, AA men with a high degree of WAA demonstrate an increased risk of PCa. Future work will focus on determining the association of known prostate cancer risk SNPs such as the 8q24 regions and genetic ancestry.