Longitudinal study of socioeconomic factors, stress-related biomarkers, and aggressive prostate cancer

Principal Investigator

Name
Kathryn Barry

Degrees
Ph.D., M.P.H.

Institution
University of Maryland, Baltimore

Position Title
Tenure-Track Assistant Professor

Email
kbarry@som.umaryland.edu

About this CDAS Project

Study
PLCO (Learn more about this study)

Project ID
2026-0158

Initial CDAS Request Approval
Jun 17, 2026

Title
Longitudinal study of socioeconomic factors, stress-related biomarkers, and aggressive prostate cancer

Summary
Data from our group and others suggest that residence in disadvantaged neighborhoods is associated with a higher likelihood of developing aggressive prostate cancer. Growing data support that chronic stress and downstream effects such as increased inflammation play a role. We previously reported that several neighborhood disadvantage metrics (neighborhood socioeconomic deprivation, racial segregation, and historical redlining) were associated with higher expression of stress-related genes in prostate tumor tissue, including several proinflammatory genes in the Conserved Transcriptional Response to Adversity (CTRA). Other research has indicated a link between neighborhood deprivation and serum protein inflammatory profiles among healthy men. However, many previous studies have been cross-sectional and research is lacking on the role of neighborhood factors in changes in stress-related markers over time using longitudinal designs. Additionally, while some previous studies have considered individual-level socioeconomic status as a potential confounder, there has been little exploration of the independent and joint effects of individual- and neighborhood-level social determinants of health with regard to stress-related biomarkers to understand their relative importance and whether individual-level factors modify associations for neighborhood-level factors. Moreover, despite potential for stress-related markers to enhance the prediction of aggressive prostate cancer, there has been little study of the predictive ability of changing stress-related biomarkers over time and the risk of aggressive prostate cancer.

Here we aim to conduct a nested case-control study of aggressive prostate cancer, leveraging longitudinal blood samples among men in the screening arm of the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. The objective of the proposed study is to evaluate the contributions of individual- and neighborhood-level social determinants of health to changes in stress-related markers (in controls) over time and the predictive value of changing stress-related markers over time for aggressive prostate cancer. The central hypothesis is that individual-level factors (e.g., income, education, marital status, and recent prostate cancer screening) will modify associations for neighborhood disadvantage metrics with stress-related biomarkers and that these stress-related markers will enhance prediction of aggressive prostate cancer beyond use of prostate-specific antigen (PSA) data. We will evaluate RNA expression of stress-related genes in the Conserved Transcriptional Response to Adversity (CTRA) and other stress-related signaling genes (i.e., genes in the serotoninergic, adrenergic, glucocorticoid, dopaminergic, and muscarinic pathways) as in our previous research. Additionally, we will include proteomic immune-related signatures that have been linked with cancer mortality among prostate cancer patients in previous work.

The proposed research will help identify individuals (based on individual and neighborhood characteristics) who are more likely to experience higher stress and worse health outcomes and may benefit from interventions to reduce stress. Additionally, if we find that stress-related markers over time enhance prediction of aggressive prostate cancer beyond PSA as hypothesized, then there will be important applications in improving screening approaches and prostate cancer outcomes.

Aims

Aim1: Multilevel modeling of neighborhood disadvantage, individual-level social determinants of health and access to care, and changes in serum stress-related biomarkers over time.
Hypothesis: Neighborhood disadvantage metrics will be associated with changes in stress-related biomarkers (RNA expression of CTRA genes and protein immune-oncological markers) in serum over time. We also hypothesize that associations will be stronger among men with lower income or education, single marital status, or no recent history of screening (as a marker of reduced access/use of care).

Aim 2: Evaluate predictive value of changing stress-related markers in serum over time for aggressive prostate cancer.
Hypothesis: Changing stress-related markers in serum over time (same markers described in Aim 1) will enhance prediction of aggressive prostate cancer beyond the use of PSA data.

Collaborators

Kathryn Barry (University of Maryland, Baltimore)
Wen-Yi Huang (National Cancer Institute)
Joseph Boyle (Virginia Commonwealth University)
Yuji Zhang (University of Maryland, Baltimore)