American Men Research Articles

Abstract 7412: The relationship between lifestyle factors and polygenic risk score with prostate cancer risk in the Multiethnic Cohort

Abstract Introduction: Behavior modifications for men at high genetic risk of prostate cancer (PCa) have the potential to prevent or delay disease onset. In this study, we evaluated whether the association of a previously developed healthy behavior score with PCa risk varies across levels of genetic susceptibility, as measured by a multi-ancestry polygenic risk score (PRS) in the Multiethnic Cohort (MEC). Methods: We conducted a nested case-control analysis of 6, 096 incident PCa cases and 24, 684 controls among African American (13%), Latino (23%), Japanese American (35%), Native Hawaiian (7%), and White (22%) men in the MEC. Among the PCa cases, 2, 049 were aggressive cases and 776 were lethal cases. We calculated the 2015 Prostate Cancer Behavior Score from the baseline questionnaire, which comprised six modifiable factors (smoking, BMI, physical activity, intake of tomatoes, processed meat, and fatty fish), with each factor scored as 1 for meeting healthy thresholds and 0 otherwise. This score ranged from 0 to 6 with a higher score indicating a healthier behavior pattern. The PRS of 451 risk variants was constructed with weights from the largest multi-ancestry genome-wide association study for PCa. In the overall study and within each racial/ethnic group, we evaluated the association of the behavior score (categorized as 0-2, 3, 4, 5-6) with risk of overall, aggressive, and lethal PCa in logistic regression analyses and assessed interactions between the behavior score and PRS (categorized as 0-50%, 50-75%, and 75-100%) on PCa risk using the likelihood ratio test (LRT). A P < 0.05 was considered statistically significant. Results: Comparing the highest to the lowest category of the behavior score (5-6 vs. 0-2), there was a suggestive 29% (95% CI: 0.47-1.04, P=0.09) lower risk of lethal PCa in the overall study. Although not statistically significant, a similar inverse association was observed in Whites (OR=0.36), Japanese Americans (OR=0.26), and Latinos (OR=0.26) but not in African Americans (OR=1.62). When stratified by PRS category in the overall study, this inverse association appeared to be stronger for men in the 75-100% PRS category (OR=0.55, 95% CI: 0.27-1.04, P=0.07) than those in the lower PRS categories (ORs 0.72-0.97, P >0.9). These differences in the association of behavior score with risk of lethal PCa across PRS categories were not statistically significant (PLRT = 0.56). No interaction was observed between the behavior score and PRS on risk of overall and aggressive PCa. Conclusion: Findings from this multiethnic study provided further support that the 2015 Prostate Cancer Behavior Score was associated with a reduced risk of lethal PCa. However, there was limited evidence that this association was modified by PCa PRS, which could be due to the relatively small number of lethal PCa cases in our study. Further investigations in larger diverse populations are warranted to confirm our findings. Citation Format: Raymond W. Hughley, Anqi Wang, Peggy Wan, Xin Xiong, Wei Xiong, David Bogumil, Song Yi Park, Lynne Wilkens, Loic Le Marchand, David Conti, Christopher Haiman, Fei Chen. The relationship between lifestyle factors and polygenic risk score with prostate cancer risk in the Multiethnic Cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 7412.

Abstract 3617: Distinct immune signature and regulated genes in prostate cancer disparity

Abstract Prostate cancer is a biologically and clinically diverse disease, with incidence and mortality rates varying significantly among different racial and ethnic groups. In African American (AA) men, the incidence of prostate cancer is approximately 60% higher, and the mortality rate is two to three times greater compared to Caucasian American (CA) men. These disparities are complex and encompass various biological and social determinants, including genetic predisposition, comorbid conditions, socioeconomic status, and environmental influences. The interplay of these elements has a clear association with disease outcomes. Recent research highlights the role of the tumor immune landscape and its associated genes in regulating prostate cancer biology at every stage of progression, ultimately impacting patient outcomes. We hypothesize that variations in immune cell gene signatures within tumors across different racial groups may influence prostate cancer outcomes. To investigate this, we analyzed transcriptomic data from 35 radical prostatectomy specimens obtained from treatment-naive patients, comprising 20 AA men and 15 CA men with prostate cancer. This analysis focused on the gene expression profiles of primary prostate tumors and adjacent normal tissues. We specifically selected immune-related genes to assess the immune-oncological differences between AA and CA prostate tumors, utilizing bioinformatics platforms such as EPIC, xCell, and IPA. To evaluate race-specific differential gene expression, we employed a rank test, and the effect of each gene’s expression on overall survival was further analyzed using a univariate Cox regression model. Prostate tumors in AA patients exhibit significant enrichment in the tumor microenvironment and a distinct gene immune profile compared to those in CA men. In AA patients we observed elevated z-scores in pathways such as CREB signaling, Th1 and Th2 pathways, dendritic cell maturation, IL-17 signaling, TREM1 signaling, and cytokine production in macrophage and T Helper cells mediated by IL-17A and IL-17F. We also noted increased cytokine levels in epithelial cells influenced by IL-17A and IL-17F. Conversely, pathways like PD-1, PD-L1, ILK, IL-3, chemokine signaling, adrenomedullin, erythropoietin signaling, IGF-1, VEGF, and B-cell receptor signaling exhibited low z-scores in AA prostate tumors. Additionally, our analysis identified 13 major immune cell types, and 27 genes significantly associated with immune cell infiltration in AA prostate cancer. The expression levels of ARSL, BAALC, CCL23, EPHA2, IGFL2, KRT5, NTM, and NDP (p < 0.05) were linked to overall survival in AA prostate cancer patients. Taken together, prostate cancer in AA patients demonstrates a unique immune repertoire and gene profile, characterized by significant enrichment in pro-inflammatory immune pathways that correlate with poorer outcomes. Citation Format: Shiv Shankar Verma, Pingfu Fu, Gregory T MacLennan, Lee E Ponsky, Chen-Han Wilfred Wu, Jonathan E Shoag, Sanjay Gupta. Distinct immune signature and regulated genes in prostate cancer disparity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3617.

Abstract 4743: Defining the impact of anti-androgen pathway inhibitors on ABI1, dendritic spines and mouse behavior

Abstract Prostate cancer (PCa) is the most commonly diagnosed cancer and the second leading cause of cancer-related deaths among American men. Following radiation therapy and surgery, patients are often treated with androgen deprivation therapy (ADT) or anti-androgen drugs to suppress tumor growth, as prostate cancer is highly androgen-dependent. However, emerging evidence highlights significant cognitive side effects, including dementia and behavioral changes, associated with anti-androgen treatments. While clinical trials are investigating these ‘treatment-induced’ cognitive deficits, the underlying mechanisms remain poorly understood. Our previous work revealed that the Androgen Receptor (AR) regulates Abelson Protein 1 (ABI1) expression in prostate tumors. ABI1, a key stabilizer of the WAVE complex, plays a critical role in actin polymerization and cytoskeletal reorganization. In dendritic spines, ABI1 supports the dynamic remodeling of the cytoskeleton essential for synaptic plasticity, a fundamental process underlying learning and memory. Disruption of ABI1 in hippocampal neurons results in abnormal dendritic spine morphology and impaired synapse formation, but there are no genetic studies on the role of Abi1 in cognitive performance in mouse models. Androgen deprivation, through surgical castration or ADT, has been shown to impair memory and behavior in mice. Given that ABI1 expression is downregulated by anti-AR therapy in prostate tumors, we hypothesize that ABI1 is similarly regulated by androgens in dendritic spines. We propose that AR suppression by ADT leads to reduced ABI1 expression in dendritic spines, contributing to cognitive and behavioral impairments in patients undergoing ADT. To test this hypothesis, we utilized a novel Abi1-selective knockout mouse model developed in our lab to explore the effects of ABI1 disruption on dendritic spines and behavior. Additionally, we compared dendritic spine morphology and ABI1 levels in the hippocampi of mice treated with anti-AR drugs, such as enzalutamide, or subjected to surgical castration. These results are being analyzed alongside findings from mice with genetic ABI1 disruption. This study provides critical insights into the role of ABI1 in dendritic spine dynamics and synaptic plasticity, uncovering a potential mechanistic link between ADT and cognitive dysfunction. Our findings aim to define the molecular basis of treatment-related cognitive deficits in PCa patients and may guide the development of strategies to mitigate these side effects. Citation Format: Anna Seidl, Kevin M. Lin, Maria A. Ortiz, Leszek Kotula. Defining the impact of anti-androgen pathway inhibitors on ABI1, dendritic spines and mouse behavior [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4743.

Abstract 1709: Cyanobacteria-derived RNA aptamer supports prostate cancer hormone sensitivity

Prostate cancer (PCa) hormone therapy resistance is the second leading cause of cancer death among American men. Multiple mechanisms inherent to the disease can lead to castrate-resistance, including those that mediate lineage plasticity. We have reported that inhibiting AR signaling can increase glutamine (L-Gln) secretion by cancer-associated fibroblasts (CAF). L-Gln-free media significantly limits PCa cell growth. However, targeting L-Gln metabolism or transporters provides limited benefit. On the other hand, non-metabolizable L-Gln analogues like 6-Diazo-5-oxo-l-norleucine (DON) and DRP104 have shown promising antitumor effects. We reasoned that extracellular interruption of L-Gln uptake could be a therapeutic strategy that bypasses metabolic adaptation of a specific enzyme or transporter, especially if it could be tumor-selective. To target L-Gln, we explored cyanobacteria-structured non-coding RNA riboswitches, which are typically associated with metabolite-binding for gene regulation. Riboswitches in cyanobacteria that sense L-Gln through an aptamer motif, glnA, were chosen due to their stability and high specificity. Since L-Gln concentrations in bacteria can be higher than those in the tumor microenvironment, we optimized an RNA aptamer binding affinity through structural analysis, computer modeling, and in vitro and in vivo testing. The optimized aptamer depleted L-Gln from PCa cells by both L-Gln sequestration and the recruitment of extracellular glutaminase activity, serving as an allosteric activator. Glutamine depletion reduced FOXM1 transcriptional occupancy on the FGF8 promoter, known mediator of PCa castrate resistance. Further tumor targeting was achieved by functionalizing gold nanoparticles with the aptamer. The L-Gln-depleting aptamer, with demonstrated serum stability, limited the proliferation, and lineage plasticity of the castrate resistant prostate tumors alone and in combination therapy with AR antagonists, enzalutamide and apalutamide in subcutaneous and orthotopic mouse models. A point mutation in the binding pocket of the 56mer rendered the aptamer ineffective in L-Gln binding, FGF8 regulation, and had a limited impact on tumor growth. Superiority of the functionalized nanoparticle targeting was demonstrated in an orthotopic PCa model over the un-targeted aptamer in reducing tumor weight. The studies demonstrated elevated L-Gln can be necessary and sufficient for castrate resistance, as its depletion sensitizes prostatic tumors to AR inhibition. Citation Format: Carlos David Cruz-Hernandez, Bethany Smith, Sandrine Billet, Manish Thiruvalluvan, Gabrielle Gonzalez, Neil Bhowmick. Cyanobacteria-derived RNA aptamer supports prostate cancer hormone sensitivity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1709.

Abstract 3910: Patient-derived conditionally reprogrammed cells in prostate cancer research

Abstract Prostate cancer (PCa) remains a leading cause of mortality among American men, with metastatic and recurrent disease posing significant therapeutic challenges due to a limited comprehension of the underlying biological processes governing disease initiation, dormancy, and progression. The conventional use of PCa cell lines has proven inadequate in elucidating the intricate molecular mechanisms driving PCa carcinogenesis, hindering the development of effective treatments. To address this gap, patient-derived primary cell cultures have been developed and play a pivotal role in unraveling the pathophysiological intricacies unique to PCa in each individual, offering valuable insights for translational research. This review explores the applications of the conditional reprogramming (CR) cell culture approach, showcasing its capability to rapidly and effectively cultivate patient-derived normal and tumor cells. The CR strategy facilitates the acquisition of stem cell properties by primary cells, precisely recapitulating the human pathophysiology of PCa. This nuanced understanding enables the identification of novel therapeutics. Specifically, our discussion encompasses the utility of CR cells in elucidating PCa initiation and progression, unraveling the molecular pathogenesis of metastatic PCa, addressing health disparities, and advancing personalized medicine. Coupled with the tumor organoid approach and patient-derived xenografts (PDXs), CR cells present a promising avenue for comprehending cancer biology, exploring new treatment modalities, and advancing precision medicine in the context of PCa. Citation Format: Abdalla Elbialy, Akshay Sood, Shang-Jui Wang, Peng Wang, Jenny Li, Xuefeng Liu. Patient-derived conditionally reprogrammed cells in prostate cancer research [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3910.

Abstract 3604: Diabetes and prostate cancer-specific mortality in the Multiethnic Cohort Study: Looking deeper into diagnostic timing and disease duration

Abstract Background: Diabetes is found to be associated with higher cancer-specific mortality for several cancers, but the findings have been conflicting for prostate cancer (PCa). The goal of this study was to evaluate the association between diabetes and PCa-specific mortality (PCSM) in a racial/ethnically diverse population of PCa patients. Methods: The association between diabetes and PCSM was assessed in 10, 464 African American (20.9%), Latino (23.6%), Native Hawaiian (5.4%), Japanese American (28.2%), and non-Hispanic White men (21.9%) diagnosed with incident PCa in the Multiethnic Cohort (MEC). Based on questionnaires and administrative data, diabetes status was defined as non-diabetic, pre-diagnostic diabetic, and post-diagnostic diabetic (relative to PCa diagnosis). In a subsequent analysis, diabetes status was further categorized given the timing of diabetes diagnosis (0-5 or > 5 years pre- or post-diagnosis of PCa). Sub-hazard ratios (SHRs) and 95% confidence intervals (CIs) were estimated using the Fine and Grey subdistribution hazards models, with time since PCa diagnosis as the time metric and adjustments on potential confounders. All analyses were performed in all PCa patients and stratified by tumor stage (localized, advanced) and Gleason score (high-grade, low-grade). Results: During an average follow-up of 8.5 years, 1, 311 (12.5%) men with PCa died of the disease. Compared to men without diabetes, men with pre-diagnostic diabetes had a significantly lower PCSM (SHR=0.73, 95% CI: 0.62-0.86) and the reduction in PCSM appeared to be greater for men with post-diagnostic diabetes (SHR=0.58, 95% CI: 0.48-0.70). Similar trends of the associations for pre- and post-diagnostic diabetes were observed among patients with high-grade (SHR 0.72 vs. 0.51) or advanced (SHR 0.72 vs. 0.56) disease. Among patients with low-grade or localized disease, the inverse associations with PCSM were similar for men with pre- (SHR 0.70-0.76) or post-diagnostic diabetes (SHR 0.65-0.75). Further categorization given the timing of diabetes diagnosis did not lead to differences in trends of the associations for pre- and post-diagnostic diabetes on PCSM among all, high-grade and advanced PCa cases. Among low-grade or localized cases, the inverse association was more evident among those with 5+ years of diabetes before cancer diagnosis and those who became diabetic within 5 years of cancer diagnosis (SHR 0.48-0.69 vs. 0.81-0.91). Statistical significance was defined as P < 0.05. Conclusions: We found that both pre- and post-diagnostic diabetes were significantly associated with a lower PCSM among PCa patients, and the association appeared to be stronger for post-diagnostic diabetes. Further studies are needed to confirm these findings in other multiethnic populations and to understand the mechanisms driving these associations. Citation Format: Wei (Melody) Xiong, David Bogumil, Peggy Wan, Gertraud Maskarinec, David V. Conti, Lynne R. Wilkens, Loïc Le Marchand, Christopher A. Haiman, Fei Chen. Diabetes and prostate cancer-specific mortality in the Multiethnic Cohort Study: Looking deeper into diagnostic timing and disease duration [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3604.

Abstract 4955: Somatic mutation frequency in prostate cancer patients of different ancestries and age of onset

Abstract Background: Prostate cancer (PCa) varies significantly in outcomes based on age of onset and genetic ancestry. Early-onset PCa (EoPCa), diagnosed in men under 55, exhibits aggressive behavior, poor differentiation, and resistance to hormonal therapies, resulting in worse outcomes compared to late-onset PCa (LoPCa). African American (AA) men face more aggressive disease and higher incidence rates than White men with European heritage (EA), even after accounting for socioeconomic factors. Investigating somatic mutations in PCa is essential to understanding disease progression, as the biology of EoPCa remains poorly defined. Comparing mutational frequencies in AA and EA men with EoPCa and LoPCa provides key insights into these disparities and informs targeted interventions. Methods: We analyzed the mutational status of EoPCa and LoPCa in AA and EA patients. We isolated DNA in tumor tissue from FFPE prostatectomy tissues using Qiagen’s FFPE DNA Purification Plus Kit. DNA samples from three patients in each cohort (AA LoPCa, AA EoPCa, EA LoPCa, EA EoPCa) were investigated for 81 somatic mutations across 13 genes using real-time PCR. Mutational analysis was performed with Qiagen’s qBiomarker Prostate Cancer Gene Panel, an assay designed to detect PCa specific sequence alterations. DNA and qBiomarker Probe Master Mix were prepared following the manufacturer’s protocol. Relative fold gene expression was calculated using the 2-∆∆Ct (delta-delta Ct) method, with DNA from normal epithelial prostate tissue serving as the control. Values exceeding a threshold of 4 were considered indicative of mutations. Results: The analysis of somatic mutation frequencies, with their position and substitution, revealed notable differences across race and the combined factors of race and age of onset. Our analysis revealed higher mutation rates in AA patients for CTNNB1 98 C>T (83.3% AA vs. 66.7% in EA) and KRAS 34 G>A (66.7% AA vs. 33.3% in EA), mutations not previously reported as elevated in AA PCa. When examining race and age of onset together, distinct patterns emerged. Among LoPCa patients, the TP53 827 C>T mutation was found in 100% of AA patients compared to 66.7% of EA patients, while the HRAS 35 G>T mutation was present in 33.3% of AA patients but absent in EA patients. In EoPCa, AA patients exhibited higher frequencies of the CTNNB1 101 G>T mutation (33.3% AA vs. 0% in EA) and KRAS 35 G>C mutation (33.3% AA vs. 0% in EA). Conclusion: These mutations, previously unexamined in the context of race and age of onset, highlight disparities in the mutational landscape of PCa. Citation Format: Tara S. Jennings, Anton N. Nguyen, Weiping Chu, Dan Mercola, Farah Rahmatpanah. Somatic mutation frequency in prostate cancer patients of different ancestries and age of onset [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4955.

Abstract 1703: Molecular drivers of enzalutamide resistance in prostate cancer: insights into CYP3A5 and associated pathways

Abstract Prostate cancer (PC) disproportionately affects Black/African American (AA) men, who experience higher incidence rates, more aggressive disease, and worse outcomes compared to non-Hispanic White Americans (NHWA). CYP3A5, a cytochrome P450 enzyme, is expressed at higher levels in individuals carrying the *1 variant, prevalent in AAs, compared to the *3 variant, more common in NHWA. Elevated CYP3A5 expression in AAs has been associated with aggressive prostate cancer phenotypes, potentially due to its role in activating androgen receptor (AR) signaling and promoting crosstalk with Wnt signaling pathways. Resistance to AR-targeted therapies, such as enzalutamide, remains a major challenge in metastatic castration-resistant prostate cancer (mCRPC), particularly in aggressive disease subtypes. To investigate mechanisms underlying enzalutamide resistance, we generated resistant PC cell lines of NHWA origin (low CYP3A5-LNCaP) and AA origin (high CYP3A5-MDAPCa2b). In resistant MDAPCa2b cells, RT2 androgen receptor profiler arrays revealed upregulation of MME, SGK1, SNAI, and STEAP, genes implicated in Wnt pathway regulation (SGK1), epithelial-to-mesenchymal transition (SNAI), and enhanced proliferation and migration (STEAP). Additionally, tumor suppressors and regulatory genes, including ADAMTS1, KLK4, MT2A, NDRG1, and TIPARP, were significantly downregulated, suggesting reduced ECM remodeling, oxidative stress responses, and DNA repair capacity in resistant cells. Importantly, CYP3A5 expressions were significantly elevated in resistant MDAPCa2b cells but remained unchanged in resistant LNCaP cells, highlighting a potential link between high CYP3A5 expressions and resistance mechanisms. The upregulation of SGK1, SNAI, and STEAP, alongside the downregulation of ADAMTS1, KLK4, MT2A, NDRG1, and TIPARP, suggests that resistance to enzalutamide involves AR and Wnt signaling, EMT, and loss of tumor suppressive functions. These findings support the hypothesis that the *1 CYP3A5 variant in AAs drives aggressive disease and therapeutic resistance, providing a molecular basis for observed clinical disparities and potential pathways for targeted intervention. Citation Format: Imran Khan Mohammed, Ranjana Mitra. Molecular drivers of enzalutamide resistance in prostate cancer: insights into CYP3A5 and associated pathways [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1703.

Abstract 980: Deaths from cardiovascular disease in rural and African American men with prostate cancer

Abstract 980: Deaths from cardiovascular disease in rural and African American men with prostate cancer

Abstract 1458: Tolerance of SOX2 and BRN2 in prostate cancer cell lines: effects on cell cycle and lineage transformation

Abstract Introduction: Prostate cancer (PCa) is the most prevalent malignancy in American men excluding skin cancer. In metastatic disease, resistance to androgen pathway inhibitors (APIs) is a major obstacle to curative treatment. One such resistance mechanism is the histological transformation from adenocarcinoma to a neuroendocrine (NE) phenotype, driven by transcription factors like SOX2 and BRN2. Of note, SOX2 is typically overexpressed in PCa lacking functional Rb and p53 and can regulate cell cycle proteins including Cyclin D1. These findings warrant an investigation into a potential connection between SOX2, the cell cycle, and tumor suppressors to further establish molecular mechanisms of neuroendocrine differentiation (NED). We also plan to investigate the potential role of BRN2 in this process. Methods: Lentiviral Tet-On® systems were cloned and transduced into the PCa cell lines LNCaP (WT RB1, WT TP53) and DU145 (RB1 -/-, TP53 mutant) for the inducible expression of SOX2 (iSOX2) and BRN2 (iBRN2). In vitro growth assays were performed by plating 5, 000 cells/well in a 96 well plate and adding doxycycline the following day (DOX). Western blots were performed to determine protein expression. Cell cycle analysis was performed by PI staining and flow cytometry. Results: Inducible models showed robust induction of SOX2 or BRN2 after 24h induction. At 4d, iBRN2 cell lines demonstrated NE marker upregulation, specifically synaptophysin. SOX2, but not BRN2, induction decreased Cyclin D1 expression irrespective of Rb and p53 status. Intriguingly, LNCaP iSOX2 cells were less viable following induction and had distinct morphological changes including the loss of their stellate shape. LNCaP iBRN2 cells had less profound, but apparent, changes in morphology. No significant morphological changes were identified in DU145. Cell cycle analysis found a greater percentage of LNCaP iSOX2 cells in the sub-G1 state and a lesser percentage in the G2/M phase versus the empty vector. Conclusions: These results suggest that SOX2 overexpression (OE) may only be tolerated in an Rb and/or p53 deficient setting. Further research will seek to determine if this phenomenon is due to SOX2-induced repression of Cyclin D1. Subsequent experiments will use RB1 and/orTP53 KO cell lines to generate new SOX2 and BRN2 inducible systems. Novel experiments will seek to determine if RB1 and/or TP53 KO increases tolerance to SOX2 OE. Connecting this knowledge of the SOX2 protein to the cell cycle and hormonal signaling in PCa may offer insight into the interplay between emerging cell cycle-targeting therapeutics and the NED process. Citation Format: Connor Purcell, Praveen R. Srinivasan, Shengliang Zhang, Maximilian Pinho-Schwermann, William J. MacDonald, Lanlan Zhou, Andrea Schmidt, Claire Lin, Xiaobing Tian, Tyler J. Roady, Vida Tajiknia, Viva Voong, Wafik El-Deiry. Tolerance of SOX2 and BRN2 in prostate cancer cell lines: effects on cell cycle and lineage transformation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1458.

Abstract 793: Cardiometabolic risk factors among Puerto Rican men with prostate cancer

Abstract Background: Cardiovascular and metabolic disorders are significant contributors to morbidity and mortality among men with prostate cancer. However, few studies characterize the association between cardiometabolic comorbidities and tumor risk in the post-operative space among high-risk groups. Like African American men, Puerto Rican men have a higher risk of developing and dying from prostate cancer than other racial and ethnic groups in the United States. As cardiovascular and metabolic risk factors are highly prevalent in Puerto Rico, we proposed to investigate coordinated risk evaluation of cardiometabolic and oncologic risk in this population. We hypothesized that a subset of cardiometabolic risk factors consistently correlate with clinically defined aggressive disease. Methods: The Puerto Rico Urology Group (PRUG) is the largest group urology practice in Puerto Rico. It currently consists of ten urologists serving the Western, Southern, Central, and Metropolitan regions of Puerto Rico including the island municipalities of Vieques and Culebra. Our cohort (n=388) of patients underwent robotic assisted radical prostatectomy for prostate cancer between 2015 and 2022. Clinical data were extracted from consented patients’ electronic health records with appropriate IRB approval (Ponce Research Institute IRB no. 2210121134, University of Puerto Rico Comprehensive Cancer Center IRB no. 2023-08-111). Post-surgical cancer of the prostate risk assessment (CAPRA-S) was used to stratify tumors and cardiometabolic risk factors were evaluated across tumor risk strata. Results: The majority of study participants had low-risk tumors (238/388, 61.3%), with intermediate tumors accounting for 106/388 (27.3%), and high-risk tumors accounting for 44/388 (11.3%). Higher CAPRA-S score was significantly associated with greater tumor mass (p<0.001), presence of perineural invasion (p<0.001), and presence of hyperlipidemia (p<0.001). Conclusion: The Puerto Rican population represents the second largest Hispanic/Latino subgroup in the United States and has disproportionately high rates of prostate cancer and cardiometabolic comorbidity. Our preliminary findings indicate that the coordinated evaluation of cancer risk in the context of high-risk disease may provide additional insights for clinicians managing prostate cancer among populations with high prevalence of these chronic diseases. These findings provide insights for ongoing studies to evaluate large, multi-institutional cohorts and identify molecular indicators of cardiometabolic risk predictive of prostate cancer aggressiveness among diverse populations. Acknowledgements: This study was supported by funding from the Puerto Rico IDeA Network of Biomedical Research Excellence (PR-INBRE, grant no. 2P20GM103475-21), awarded to C.J.D.O. through the Developmental Research Projects Program. Citation Format: Valeria Torres Matos, Katherine Carrero Figueroa, Noemi Santiago, Julie Dutil, William Roman Torreguitart, Carlos Joel Diaz Osterman. Cardiometabolic risk factors among Puerto Rican men with prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 793.

Countering Deficits: Relational Sanctification, Forgiveness, and Family Functioning Among Older, Romantically Involved African Americans.

Despite the significance of romantic relationships in later life, relatively little research has focused on older African Americans, a population highly engaged in religious behaviors. Forgiveness often mediates the relationship between relational sanctification and various positive relational outcomes. This study examined forgiveness as a mediator between relational sanctification and family functioning among older African American couples. It used dyadic data from 194 African American couples aged 50 to 86. The relationships between men's relational sanctification and men's reports of family functioning were partially mediated by men's self-reported ability to forgive their partner (B = .045) and the sum of all men's and women's reported abilities to forgive and perceive forgiveness (B = .124). However, these associations were not statistically significant for women. These findings highlight the growing yet underrecognized need to understand the religiosity of older African American men relative to positive relational outcomes.

Impact of Disclosing to Patients the Use of Antiretroviral Resistance Testing Results for Molecular HIV Surveillance: A Randomized Experiment in 2 National Surveys.

Molecular HIV surveillance (MHS) can be used to help identify and respond to emerging clusters of rapidly spreading HIV transmissions, a practice known as cluster detection and response (CDR). In the United States, MHS relies on HIV gene sequences obtained from routine clinical antiretroviral resistance testing (ARVRT). By law, ARVRT results are reported to public health agencies for MHS and individuals are not asked for their specific consent to do so. This practice has raised ethical concerns, including the lack of consent for, and transparency surrounding, public health uses of these clinical data. Such concerns have spurred debate and could have a chilling effect on the willingness of people living with HIV to agree to ARVRT when recommended clinically and jeopardize the utility of MHS-informed HIV prevention efforts. In response to the lack of routine disclosure of use of ARVRT results for MHS, in 2022, the Presidential Advisory Council on HIV/AIDS (PACHA) issued a resolution calling on the US Centers for Disease Control to "require that providers explain MHS/CDR and the laboratory test results that are collected and used in these surveillance activities to their patients." This study aimed to examine the effect of clinician disclosure of the public health uses of ARVRT results for MHS versus clinician nondisclosure on patient willingness to undergo recommended ARVRT. We conducted a randomized survey experiment examining the effect of clinician disclosure of the public health uses of ARVRT results for MHS versus clinician nondisclosure (the current standard of care) and subsequent discovery of such uses through a "trusted media source" on patient willingness to undergo recommended ARVRT. Study participants were respondents to 1 of 2 national web-based surveys conducted annually in the United States: the American Men's Internet Survey (AMIS) and the Transgender Women's Internet Survey and Testing (TWIST). Overall, 4348 AMIS participants (n=2151 disclosure; n=2197 nondisclosure) and 3314 TWIST participants (n=1670 disclosure; n=1644 nondisclosure) completed survey items regarding the randomly assigned vignettes. The majority were willing to undergo ARVRT regardless of which vignette they saw (1670/2151, 82.7% [AMIS] and 1326/1670, 80.8% [TWIST] in the disclosure group; and 1399/2197, 68% [AMIS] and 1101/1674, 68.45% [TWIST] in the nondisclosure group) after later learning about public health uses of ARVRT results. The majority of respondents expressed willingness to undergo ARVRT even with disclosure of public health uses of these data, but willingness markedly decreased when learning about these uses after the fact, highlighting the importance of transparency in MHS programs. Accordingly, in line with the ethical principle of respect for autonomy and the likelihood that the potential public health benefits of MHS programs will not be compromised, consideration should be given to encouraging clinicians to disclose public health uses of ARVRT at the time ARVRT is recommended.

Of race and romance: A qualitative investigation of queer Asian American men’s romantic relationships with queer Asian American men

Past research has identified that internalized racism affects Asian Americans’ dating preferences; however, fewer studies have sought to examine Asian Americans who choose to date one another. For queer Asian American men, dating fellow Asian American men may represent a rejection of idealizing White men in romantic relational contexts. The present study thus utilized a grounded theory qualitative methodology with a strengths-based approach to understand the lived experiences of queer Asian American men who are currently in romantic relationships with fellow queer Asian American men. Queer Asian American men who are in romantic relationships with other queer Asian American men from across the United States ( N = 10) participated in a semi-structured interview. Analyses identified a four-category empirical framework capturing queer Asian American men’s experiences being in a romantic relationship with fellow queer Asian American men. The core theme, Race and Romance, emphasized factors that motivate queer Asian American men to initiate and sustain romantic relationships with fellow queer Asian American men. The remaining four themes were (i) Factors contributing to dating an Asian American man, (ii) Benefits of dating a fellow queer Asian American man, (iii) Challenges of dating a fellow queer Asian American man, and (iv) Attitudes toward Asian/White interracial relationships. Participants provided insights into how queer Asian American men’s romantic relationships with one another serve as a source of liberation from White supremacy within the broader LGBT+ community.

Associating serum testosterone levels with African ancestral prostate cancer health disparities

Serum testosterone levels decrease in the aging male, while the risk for prostate cancer (PCa) increases concomitantly. Higher levels in younger men have been linked with racially driven PCa disparities, with African men disproportionately impacted. In turn, higher levels of serum lipids have been associated with aggressive disease, while racial disparity between serum testosterone, cholesterol and cancer mortality has been suggested. Having previously reported a 2.1-fold increased age-adjusted risk for aggressive PCa in Black South African over Black American men, we determined the serum testosterone and associated lipid levels in 250 Black South African men either with or without clinicopathologically diagnosed disease. Observing no associations with serum lipid levels, Black South Africans presented with testosterone levels between 1.24 (< 60 years) and 1.3-fold (≥ 60 years) greater than Black Americans. Notably, a rapid drop in total-, bioavailable- and free testosterone levels in men 65 years or older was significantly associated with PCa risk (P = 0.0057, 0.009 and 0.005, respectively), while irrespective of age, further associated with advanced disease (P = 0.004, 0.0012 and 0.0036, respectively). These preliminary data provide insights into the potential role of androgens in driving PCa health disparities, with important consequence for tailoring treatment for Black men.

Deadly mass methanol poisoning in Laos

In November 2024, a suspected methanol poisoning event in Vang Vieng, Laos, made international headlines after two Australian women had fallen ill. The two women were last seen well on 12 November before being found by concerned hotel staff at the ‘Nana Backpacker Hostel’ when they did not leave their room the following day. On the same day, two Danish females were found unconscious in their rooms and were transported to a hospital in Vientiane, where they were declared deceased. By 21 November, both the Australian women and a British female were declared deceased. Then, an American man died after being found with bottles of empty and unopened spirits by his bedside. The mass poisoning event hospitalised at least 11 other people and prompted an investigation by the Lao authorities. Police identified a factory outside Vientiane where the suspected tainted alcohol was being produced and arrested the owner on 1 December. A further three staff from the hostel were also arrested on the same day in connection with the deadly poisoning. Subsequently, Tiger Vodka and Tiger Whiskey have been banned from sale across the country. Methanol poisoning events are not uncommon. Many deadly poisoning events have occurred across the globe in recent years. In many countries where home production or artisanal small-scale production of alcoholic beverages is traditional, this distillation process can lead to dangerous bootleg alcohol being produced. Furthermore, counterfeit alcohol is often sold around the globe and bought unknowingly. There is no public early warning surveillance system capturing global methanol poisonings and alerting public health officials to investigate and implement public health measures. Given the widespread problem, it would be timely to consider establishing such a system.

Exploring empathy and patient-centered communication behaviors of third-year medical students during a clinical skills examination.

Exploring empathy and patient-centered communication behaviors of third-year medical students during a clinical skills examination.

Eating disorders among an online sample of Canadian and American boys and men.

Eating disorders among an online sample of Canadian and American boys and men.

Trends and Disparities in Prostate Cancer Mortality in the United States (1999-2020).

Trends and Disparities in Prostate Cancer Mortality in the United States (1999-2020).

A Remote Physical Activity Intervention Tailored to Rural Men: A Proof-of-Concept Study

ABSTRACT Introduction This study aimed to test the preliminary efficacy and acceptability of a physical activity intervention tailored to rural men. Methods A nationwide sample of rural American men were recruited to participate in a theory-guided, 10-wk, remote physical activity intervention. The intervention was tailored to rural men’s preferences based on findings of a needs assessment study. Steps, muscle-strengthening behaviors, muscular endurance, and psychosocial outcomes were measured at baseline and post-intervention. Likert scales, open-ended survey questions, and focus groups were used to assess acceptability. Continuous data were analyzed using a t-test and Wilcoxon signed-ranked test, and dichotomous variables were analyzed using a McNemar test. Results A total of 27 (39 consented, 27% attrition) mostly White, non-Hispanic rural men completed the intervention. On average, participants completed 8.0 ± 4.4 (out of the 11 provided) modules over the 10-wk intervention period, and 15 participants (56%) completed all 11 modules. The proportion of participants engaging in muscle strengthening behavior increased from 18.5% to 69.2% (P = 0.003). Push-up (P &lt; 0.001), sit-up (P = 0.004), and squat (P &lt; 0.001) tests significantly improved. Behavior regulation (Hedges’ g = 1.23, P &lt; 0.05) and physical activity identity (Hedges’ g = 0.85, P &lt; 0.05) increased from baseline to 10 wk. On average, all features were rated at least somewhat helpful. Conclusions The intervention improved rural men’s muscle strengthening behaviors, muscular endurance, behavioral regulation, and physical activity identity, but not steps. Future studies can expand on this work by improving intervention features, such as greater accountability, and comparing the intervention against a control group.