A study evaluates the polygenic risk score for prostate cancer risk prediction. VUMC Reporter

Lee Macmillan

Prostate cancer polygenic risk score (PRS) has limited utility in enhancing prostate cancer screening, according to new paper study was announced in JAMA Internal Medicine.

Researchers at Vanderbilt University Medical Center are investigating whether the prostate cancer PRS, an indicator of an individual’s “burden” of genetic mutations associated with prostate cancer, can improve risk prediction compared to available clinical risk calculators. led a study to assess whether PRS for prostate cancer improved the detection of all prostate cancers but not the prediction of aggressive cancers.

According to the American Cancer Society, prostate cancer is the second leading cause of cancer-related death in men. About 1 in 8 men will be diagnosed with prostate cancer in his lifetime.

Although screening strategies based on prostate-specific antigen (PSA) and other factors have been developed, biopsies often find low-grade cancers with minimal risk and no need for treatment.

“Low-grade prostate cancer diagnosis contributes to increased medical costs, patient anxiety, and invasive procedures with the potential for serial biopsies,” he said. Kelly Shaffer, MD, MSCI, Assistant Professor of Medicine, Division of Hematology and Oncology, and co-first author of the new report. “There is a strong interest in identifying biomarkers and tools to better distinguish advanced cancers from low-grade tumors to guide decision-making regarding prostate biopsies.”

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

“Incorporating polygenic risk scores that measure the burden of these risk-associated variants may improve risk prediction models,” he said. Jonathan MosleyMD, PhD, Associate Professor of Medicine in the Department of Clinical Pharmacology, and senior corresponding author of the study.

“We compared the performance of the extensively validated multiethnic prostate cancer PRS with a modern and widely used clinical tool, the PBCG risk calculator, to risk stratify individuals for advanced prostate cancer. bottom.

The Prostate Biopsy Collaborative Group (PBCG) Risk Calculator uses age, PSA, digital rectal exam findings, family history, and family history to assess the risk of 1) any cancer and 2) any cancer in men undergoing an initial prostate biopsy. Estimate the probability of finding an aggressive cancer.

Schaffer and co-first author MingjianPhD, a staff scientist in the Department of Biomedical Informatics, led a retrospective study involving 655 men of African and European ancestry aged 40-80 years without prostate cancer who underwent prostate biopsy. Participants were selected from BioVU, VUMC’s DNA biobank linked to anonymized electronic medical records.

The researchers found that adding PRS to the PBCG predictor improved discrimination of all cancers, but not advanced cancers.

The findings suggest that “this prostate cancer PRS has limited current clinical utility for guiding the decision to perform a diagnostic biopsy and is inferior to current clinical tools.” said Mosley.

The authors noted that the strength of their study was the use of a modern PRS based on multiancestral GWAS, and that the study had a wider ancestry group and clinically relevant age range compared to previous studies. It states that it is to include groups.

“Although only 8% of our population are of African ancestry, we intend to use these data to contribute to an important and evolving literature that includes groups often underrepresented in genetic research. We included it for the purpose,” said Schaffer. “As PRS evolves in the field, research that includes racially diverse populations is essential to prevent the current inequities in genomics from escalating.

“Researchers at Vanderbilt University have participated in numerous projects related to PRS and disease risk. Studies like these are critical to assessing whether new clinical tools actually enhance care.” are emphasizing.”

other authors of JAMA Internal Medicine Reporting includes John Shelley and Jeffrey Tosoian, MD, MPH from VUMC, Linda Kachuri, PhD, and John Witte, PhD from Stanford University. This research was supported by the National Institutes of Health (grant grants GM130791, CA241410). VUMC’s BioVU is Supported Institutionally funded, privately funded, and federally funded.