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 conducted 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 overexpressed specifically in PCa from AAM relative to EAM and 132 were overexpressed in PCa from EAM relative to AAM. Furthermore, systems-level analyses highlight the relevant signaling pathways and functions associated with the EAM- or AAM-specific overexpressed gene sets, for example, 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.

A Biopsy-based 17-gene Genomic Prostate Score Predicts Recurrence After Radical Prostatectomy and Adverse Surgical Pathology in a Racially Diverse Population of Men with Clinically Low- and Intermediate-risk Prostate Cancer

“…Several studies have highlighted molecular differences in PCa in AA and Caucasian men [22] including prevalence of transmembrane protease, serine 2/v-ets avian erythroblastosis virus E26 oncogene homolog (TMPRSS2-ERG) fusions [23] and phosphatase and tensin homolog (PTEN) deletions [24], and gene expression patterns [25]. Studies also suggest that increased androgen signaling is seen in AA men [26].…”

Trends in the Incidence of Fatal Prostate Cancer in the United States by Race

“…Genetics and the tumor microenvironment may explain a majority of racial disparities seen in prostate cancer. [25,26] Fine-mapping in men of African ancestry in the 8q24 region, which is known to harbor multiple prostate cancer susceptibility risk variants, has identified three new ancestry-specific risk variants. [27]…”

The Role of Inflammation in Prostate Cancer

“…Similar findings to the Glasgow studies are apparent in studies aiming to determine why men of African American (AA) race are two to three times more likely to die from prostate cancer that European Americans (EA) (Horner et al 2009). Gene expression microarray studies of prostate cancer tissues from AA and EA men have consistently shown overexpression of gene sets involving inflammation pathways in AA samples (Powell et al 2013;Reams et al 2009;Wallace et al 2008). This includes differentially expressed gene clustering in pathways involved in immune response, interleukins, and cytokine signaling and overexpression of specific genes such as IL-6, IL-8, and IL-1β (Powell et al 2013;Reams et al 2009;Wallace et al 2008).…”