Differential DNA methylation in the benign and cancerous prostate tissue of African American and European American men.

Abstract

Background: African American (AA) men are at increased risk of prostate cancer (PCa) compared to men of European ancestry (EA). Biological mechanisms, including epigenetics, likely contribute to this disparity, but prior studies have been limited by sample size, candidate gene approaches, or lack of epigenome-wide DNA methylation (DNAm) data.

Methods: To improve our understanding of these mechanisms, we compared DNAm features distinguishing tumor and paired histologically benign tissue from 76 AA and 75 EA PCa patients. We measured genome-wide array-based DNAm data and conducted differential methylation analyses comparing tumor and benign tissue in each ancestry group. We then examined the predictive ability of our identified sites and differential methylation by ancestry group in each tissue.

Results: We identified 90,747 and 98,929 differentially methylated CpGs (dmCpGs) in AA and EA respectively with 76,400 common to both groups. We identified 6,267 genes with differentially methylated promoters common to both ancestries and 639 and 1,301 genes unique to AA and EA respectively as well as differentially methylated pathways. Only 10 CpGs were needed to distinguish tumor from benign based on a receiver operating characteristic curve (area under the curve, AUC>0.9), with dmCpGs in one ancestry predicting tumor vs benign in the other group. We also identified ancestry-associated CpGs (89 in tumor, 423 in benign).

Conclusions: Methylation features distinguishing tumor and benign were similar for EA and AA men; however, subtle differences were identified.

Impact: Differences in tumor and ancestry-associated CpGs may reveal differential tumor growth strategies, an important area for future disparities research.