Study evaluates polygenic risk score for prostate cancer risk prediction

A prostate cancer polygenic risk score (PRS) has limited utility for enhancing prostate cancer screening, according to a new study published in JAMA Internal Medicine.

Vanderbilt University Medical Center researchers led the study to evaluate whether a prostate cancer PRS, an indicator of an individual’s “burden” of prostate cancer-associated genetic variants, could improve risk prediction compared to an available clinical risk calculator. While the prostate cancer PRS improved detection of all prostate cancers, it did not improve prediction of aggressive cancers, the researchers found.

Prostate cancer is the second leading cause of cancer-associated death in men, according to the American Cancer Society. About one in eight men will be diagnosed with prostate cancer during his lifetime.

Although screening strategies based on prostate-specific antigen (PSA) and other factors have been developed, biopsies often find low-grade cancers that pose minimal risk and do not warrant therapy.

“Low-grade prostate cancer diagnoses contribute to increased health care expenditures, patient anxiety and invasive procedures with potential for serial biopsies,” said Kerry Schaffer, MD, MSCI, assistant professor of Medicine in the Division of Hematology and Oncology and co-first author of the new report. “There is strong interest in identifying biomarkers and tools to better discriminate aggressive cancers from low-grade tumors in order to guide decision-making about prostate biopsies.”

Prostate cancer is a highly heritable disease, and genome-wide association studies (GWAS) have identified numerous common genetic variants associated with increased prostate cancer risk.

“Incorporating polygenic risk scores that measure the burden of these risk-associated variants could improve risk prediction models,” said Jonathan Mosley, MD, PhD, associate professor of Medicine in the Division of Clinical Pharmacology and senior corresponding author of the study.

“We compared the performance of an extensively validated multiethnic prostate cancer PRS against a contemporary and widely utilized clinical tool, the PBCG risk calculator, to risk-stratify individuals for aggressive prostate cancer,” Schaffer said.

The PBCG (Prostate Biopsy Collaborative Group) risk calculator uses age, PSA, digital rectal exam findings, ancestry and family history to estimate the probability of finding 1) any cancer and 2) aggressive cancer in men undergoing a first prostate biopsy.

Schaffer and co-first author Mingjian Shi, PhD, staff scientist in the Department of Biomedical Informatics, led the retrospective study, which included 655 men of African and European ancestries ages 40-80 years without prostate cancer who underwent a prostate biopsy. Participants were drawn from BioVU, VUMC’s DNA biobank linked to de-identified electronic health records.

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