Comprehensive Genetic Risk Score May Predict Risk of Developing Metastatic Prostate Cancer or Death From Prostate Cancer Across Diverse Populations

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A new screening tool (called PHS290) that incorporates 290 inherited genetic variants associated with prostate cancer was able to accurately identify people with high vs low lifetime risks of developing metastatic prostate cancer or dying from prostate cancer. These findings of a genetic risk analysis, including almost 600,000 male veterans, will be presented by Pagadala et al at the 2022 ASCO Genitourinary Cancers Symposium (Abstract 155), taking place February 17 to 19 in San Francisco, as well as online.  

Men with PHS290 scores in the top 20% had a 4.4 times higher risk of death compared to those with a genetic risk score in the lowest 20%. The risk of developing prostate cancer or having metastatic prostate cancer was 5.6 times higher and 4.18 times higher for those in the top 20% of risk scores vs those in the lowest 20%, respectively.

Men with African ancestry had a 1.84 times greater risk of developing prostate cancer compared with people of European ancestry. The risk of prostate cancer metastasis was 2.27 times greater and the risk of death from prostate cancer was 1.97 times greater in patients with African ancestry compared to those with European ancestry, respectively.

Implications for Risk Assessment

“While most prior genetic studies have focused on men of European ancestry, our scoring algorithm is a measure of risk of dying of prostate cancer in a diverse population of military veterans,” stated lead author Meghana Pagadala, of the VA Health Care System, La Jolla, California, and an MD/PhD candidate at the University of California, San Diego. “Even accounting for family history and ancestry, the scoring algorithm provided powerful additional information about a man’s risk of death due to prostate cancer.”

Robert Dreicer, MD, MS, MACP, FASCO

Robert Dreicer, MD, MS, MACP, FASCO

Commenting on this study, Robert Dreicer, MD, MS, MACP, FASCO, ASCO Expert in genitourinary cancers, said: “Current prostate cancer screening recommendations rely on family history as well as race and ethnicity factors, which don’t fully capture a person’s risk of developing or dying from prostate cancer. This new study suggests that an extensive genetic risk score could be an effective tool to guide screening decisions by identifying people at high or low risk of developing metastatic prostate cancer. Importantly, this tool has been validated in a diverse population.”

The scoring algorithm is not yet commercially available.

Study Details

The study was based on data from 582,515 men enrolled in the Million Veterans Study comprising men who receive medical care at 1 of the 63 facilities that are part of the Veterans Health Care System in the United States. About 450,000 had European ancestry and 105,000 had African ancestry; the remaining people were of Asian or Hispanic heritage. Median age was 69 years, and all men consented to donate blood for genotyping.

The study protocol called for analysis of age at diagnosis and sequencing data of 290 variants for prostate cancer that increased the risk of death due to the disease. An advantage of this study is that the scoring algorithm relies on almost 300 inherited genetic variants associated with prostate cancer, whereas other genetic studies are based on expression of a dozen or so cancer-related genes and several reference genes.

“Heritable genetic information does not change over a person’s lifetime, whereas tumor gene expressions can be highly variable and are only available once a man has developed the disease. This algorithm was developed to predict the risk of prostate cancer at different ages,” said Dr. Pagadala.

The risks for people of Hispanic ancestry tracked closely with those of European ancestry, while the number of Asian patients was too small to determine a reliable estimate of risk.

Future plans are to study more ancestry-specific prostate cancer risk variants and gain a better understanding of how to incorporate ancestry into estimating genetic risk. The researchers also plan to analyze the interaction of genetic risk and environmental factors.

Disclosure: For full disclosures of the study authors, visit

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