Kevin J. Gleason

Supplementary Table S8 shows the gene-ontology enrichment results for differentially methylated CpGs identified in all genomic regions in African American and European American men

Supplementary Figure S4 shows the distribution of the post-QC CpGs across EPIC Infinium I and Infinium II assays, chromosomes, and genomic regions including CpG islands and transcription start sites.

Supplementary Table S5 shows genes identified in both AA and EA, based on differentially methylated CpGs that were previously identified as differentially methylated in Prostate Cancer.

Supplementary Figure S1 shows the results of a Principal Component Analysis of participant SNP genotypes, demonstrating separate clusters of those with African American and European American ancestry.

Supplementary Figure S2 shows a Principal Component Analysis of DNA methylation in the benign and tumor tissue of African American and European American individuals, demonstrating tissue type as the largest source of variation (A&B). Additionally, it shows that within tumor samples PC1 is associated with Gleason Score (C).

Supplementary Figure S6 shows the distribution of differentially methylated CpGs across the genome in African Americans and European Americans compared with the overall probe distribution of the tested EPIC array CpGs.

Supplementary Figure S5 shows a dendogram demonstrating the initial clustering analysis based on all post-QC probes in which there is sample clustering by tissue type.

Supplementary Table S11 shows the regional distribution of differentially methylated CpGs between African American and European American men in Tumor and Benign Tissue compared with the regional CpG distribution of the overall EPIC array

Supplementary Table S9 shows gene-ontology enrichment results for hypomethylated differentially methylated CpGs identified the promoter region of African American and European American men

Background:African American (AA) men are at increased risk of prostate cancer compared with European American (EA) men. 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 patients with prostate cancer. We generated genome-wide array-based DNAm data and conducted differential methylation analyses comparing tumor and benign tissues in each ancestry group. We then examined the predictive ability of our identified sites and differential methylation by ancestry group.Results:We identified 90,747 and 98,929 differentially methylated CpGs 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 (AUC > 0.9), with differentially methylated CpGs in one ancestry accurately predicting tumor versus 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.