Multi-population study of serum protein biomarkers and prostate cancer risk

Principal Investigator

Name
Sonja Berndt

Degrees
Pharm.D., Ph.D.

Institution
National Cancer Institute

Position Title
Senior Investigator

Email
berndts@mail.nih.gov

About this CDAS Project

Study
PLCO (Learn more about this study)

Project ID
2026-0154

Initial CDAS Request Approval
Jun 17, 2026

Title
Multi-population study of serum protein biomarkers and prostate cancer risk

Summary
Prostate cancer is the second most commonly diagnosed cancer in men and a leading cause of male cancer deaths globally. Despite its substantial impact on public health, there is currently no clear evidence-based advice that men can be given to reduce their risk of developing the disease. Established risk factors that include older age, family history, ethnicity, and genetic predisposition are not modifiable and no clear evidence yet exists for the role of other common modifiable risk factors, such as body fatness, diet, and smoking in prostate cancer etiology, limiting options for primary prevention. Moreover, some prostate cancers never progress to clinically significant disease, while others become lethal. Understanding what drives these more dangerous forms of disease is crucial. Identifying the underlying biological pathways may ultimately help us pinpoint new biomarkers or pathways to target in future interventions that could reduce the risk of aggressive disease, especially in multi-ethnic populations who are under-represented in most large biomarker studies. Recent advances in proteomic technologies now allow the measurement of thousands of circulating proteins. Proteins govern many vital cellular functions, and identifying those causally linked to disease may highlight new preventive targets. Recent studies have identified several immune and inflammation-related proteins to be associated with prostate cancer risk, provided new biological information about prostate cancer etiology and the role of immunosurveillance. However, larger studies encompassing multiple populations are needed to fully characterize these findings, discover new protein associations, and elucidate their underlying biological mechanisms for prostate cancer prevention. We propose to conduct a multi-population study to investigate circulating proteins as novel risk factors for prostate cancer. Leveraging epidemiological and biorepository resources across multiple prospective cohorts and cutting-edge proteomic technologies, we aim to uncover the role of circulating proteins in the development of prostate cancer, focusing on proteins that may distinguish aggressive disease from more indolent disease. We will analyze pre-diagnostic plasma samples across multiple different cohorts, including the PLCO Cancer Screening Trial, to identify and validate key protein markers associated with prostate cancer risk, integrate genetic data to assess causal pathways, and develop refined risk prediction models that incorporate protein biomarkers, established risk factors, and multi-omic data.

Aims

Aim 1: To assess the association of proteomics with prostate cancer risk across multiple populations. We will evaluate associations between individual proteins and prostate cancer risk using pre-diagnostic plasma samples from prospective cohorts, including the PLCO Cancer Screening Trial. We will focus on proteins associated with aggressive disease and assess potential effect modification by age at diagnosis, time of blood collection relative to diagnosis, and other risk factors.

Aim 2: To assess the role of genetics as a link between proteomics and prostate cancer risk. We will conduct a protein quantitative trait (pQTL) analysis using existing genome-wide association study data. We will conduct mediation analyses to investigate whether measured proteins mediate the association of genetics with prostate cancer.

Aim 3: To generate integrated risk prediction models for prostate cancer. We will develop risk prediction models, integrating proteomic data with data on rare and common genetics, as well as family history and PSA screening.

Collaborators

Sonja Berndt (National Cancer Institute)
Hyokyoung Hong (National Cancer Institute)
Charles Breeze (National Cancer Institute)