Genes associated with prostate cancer are differentially expressed in African American and European American men

Abstract

Background:Despite more aggressive screening across all demographics and gradual declines in mortality related to prostate cancer (PCa) in the United States, disparities among populations persist. A substantial proportion of African American men (AAM) have a higher overall incidence, earlier age of onset, increased proportion of clinically advanced disease and increased bone metastases and mortality from PCa compared to European American men (EAM). Limited early evidence indicates that underlying causes for disparities may be observed in tumor-specific gene expression programs. Methods:This study used microarray-based methods to measure expression levels for 517 genes that were previously associated with PCa in archived formalin-fixed paraffin embedded (FFPE) specimens; testing the hypothesis that gene expression features of functional consequence to cancer distinguish PCa from AAM and EAM. A t-test was performed comparing AAM to EAM expression levels for each probe on the array. Results:Analysis of 639 tumor samples (270 AAM, 369 EAM) showed that 95 genes were over-expressed specifically in PCa from AAM relative to EAM and 132 were over-expressed in PCa from EAM relative to AAM. Further, systems-level analyses highlight the relevant signaling pathways and functions associated with the EAM or AAM-specific over-expressed gene sets, e.g., inflammation and lipid metabolism. Conclusions:Results here bring further understanding to the potential for molecular differences for PCa in AAM versus EAM. Impact:The results support the notion that therapeutic benefits will be realized when targeted treatments are designed to acknowledge and address a greater spectrum of PCa subtypes and molecular distinctions.