What is the clinical evidence from this study?

Study design: Cross-Sectional. Population: Prostate cancer (n=92). Intervention: Residence in a historically redlined neighborhood vs. Residence in a non-redlined neighborhood. Primary outcome: Prostate tumor DNA methylation (DNAm) levels (p=<0.05).

What question did this study set out to answer?

To investigate the association between historical redlining and DNA methylation alterations in prostate tumors among African American men.

April 19, 2026

Abstract LB376: Historical redlining and DNA methylation in prostate tumors

Q: What are the key findings of this study?

Residence in a historically redlined neighborhood was associated with significant prostate tumor DNA methylation differences at 12 CpG sites in African American men (FDR-adjusted p<0.05).

Q: What question did this study set out to answer?

To investigate the association between historical redlining and DNA methylation alterations in prostate tumors among African American men.

Key Result

Residence in a historically redlined neighborhood was associated with significant prostate tumor DNA methylation differences at 12 CpG sites in African American men (FDR-adjusted p<0.05).

Key Points

To investigate the association between historical redlining and DNA methylation alterations in prostate tumors among African American men.
Cross-sectional study of prostate tumor DNA methylation data from African American men with prostate cancer.
Determined historical redlining status using 1930s redlining maps and patient address.
Measured DNA methylation using Illumina's EPIC v2 array and identified differentially methylated regions with bumphunter R package.
Applied linear regression to estimate associations, adjusting for age and year of surgery.
Included 92 African American men with a median age of 60 years at surgery.
Residence in a historically redlined neighborhood was linked with significant DNA methylation changes at 12 CpG sites.
10 out of 12 CpG sites exhibited hypomethylation, particularly notable at the ZDHHC19 gene (mean DNAm: 0.76 redlined vs. 0.92 non-redlined).
One significant differentially methylated region involving hypomethylation of TNXB, associated with tumor progression, was identified.

Study Design

Type

Cross-Sectional (n=92)

Multicenter

Structured PICO

Is residence in a historically redlined neighborhood associated with prostate tumor DNA methylation alterations in African American men with prostate cancer?

Population

92 African American men with prostate cancer who received radical prostatectomy at the University of Maryland Medical Center between 1992-2021, median age 60.

Intervention

Residence in a historically redlined neighborhood (based on 1930s Home Owners' Loan Corporation map of the Baltimore metropolitan area)

Comparator

Residence in a non-redlined neighborhood

Outcome

Prostate tumor DNA methylation (DNAm) alterations at 683,765 CpG sitessurrogate

Residence in historically redlined neighborhoods is associated with specific epigenetic alterations in prostate tumors among African American men, suggesting a biological mechanism linking structural racism to cancer disparities.

Main Result

p-value: p=<0.05

Abstract

Abstract Introduction. Growing literature demonstrates a role of neighborhood disadvantage (ND), which disproportionately affects African American (AA) men, in prostate cancer (PC) disparities by race. One component of ND is historical redlining, which involved the systematic denial of mortgages in certain urban neighborhoods, often based on race. Redlining led to disinvestment and subsequent ND over time, and has been linked with poorer health outcomes in the present day. Epigenetic perturbations related to chronic stress may play a role in these associations. We hypothesized that residing in a formerly redlined neighborhood would be associated with prostate tumor DNA methylation (DNAm) alterations. Methods. This cross-sectional study leveraged prostate tumor DNAm data for AA men with PC who received radical prostatectomy at the University of Maryland Medical Center between 1992-2021. Historical redlining status was determined by intersecting participants' address at diagnosis with the 1930s Home Owners’ Loan Corporation redlining map of the Baltimore metropolitan area. DNAm was measured using Illumina’s EPIC v2 array. After quality control steps, there were 683, 765 CpG sites for analysis. Linear regression models were used to estimate associations between historical redlining and DNAm levels (beta values, ranging from 0-1), adjusting for age at surgery and year of surgery. Differentially methylated regions (DMRs) were identified using the bumphunter R package. Results. We included 92 AA men with a median (interquartile range, IQR) age of 60 (54-63) years at surgery. Eight men (9%) lived in a historically redlined neighborhood. Residence in a redlined neighborhood was significantly associated with DNAm at 12 CpG sites after adjustment for multiple comparisons False Discovery Rate (FDR) -adjusted p0. 05, 10 of which exhibited hypomethylation IQR for difference: (-0. 14, -0. 07). These sites annotated to nine genes: PLEKHG5, KDR, ZDHHC19, ZNF316, ZFYVE21, CDH26, HPCA, FAM228B, PTPRN2. The most significant CpG site (cg11384525) was in ZDHHC19, which plays a role in tumor progression via S-palmitoylation activity (mean DNAm for men in redlined vs. non-redlined neighborhoods: 0. 76 vs. 0. 92; p=6. 4x10-9; FDR-adjusted p=2. 2x10-3). We identified one significant DMR involving hypomethylation of TNXB, which encodes an extracellular matrix glycoprotein that is associated with tumor progression for several cancers, including PC. Discussion. In this study of AA men with PC, tumor DNAm levels at 12 CpG sites were significantly different among men who resided in historically redlined neighborhoods. This study is one of the first to suggest associations of historical redlining with prostate tumor DNAm. Additional research is needed to replicate these findings and further investigate the relationships between the neighborhood environment, epigenetic tumor modifications, and PC disparities to elucidate mechanisms and inform interventions. Citation Format: Joseph Boyle, Camryn Cohen, Derrick Butts, Jimmie L. Slade, Yuji Zhang, Teklu B. Legesse, Ashley Johnson, Kimberly Clark, Jessica Wimbush, Nicholas Ambulos, Jing Yin, Jong Y. Park, Eberechukwu Onukwugha, Arif Hussain, Cheryl L. Knott, Kathryn H. Barry. Historical redlining and DNA methylation in prostate tumors abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts) ; 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86 (8Suppl): Abstract nr LB376.

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