Abstract PR007: Neighborhood socioeconomic deprivation, racial segregation, and prostate tumor RNA expression of stress-related genes among African American and European American men

Abstract

Abstract 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<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<0.001; q=0.02). RI scores were positively and significantly associated with expression for 7 genes (p<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<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.