Novel genetic risk score may help guide prostate cancer screening decisions

The novel PHS290 genetic risk score successfully stratified a diverse group of prostate cancer patients for their lifetime risk of metastatic or fatal disease, suggesting the tool can inform individualized screening decisions.^1,2

The PHS290 polygenic hazard score is based on 290 genetic variants linked with prostate cancer risk. Results from the study of PHS290, which were shared during the 2022 ASCO Genitourinary Cancers Symposium, showed that patients with a PHS290 score in the top 20% of genetic risk had a 4.41 times higher risk of death compared with patients in the lowest 20%. The overall risk of developing prostate cancer was 5.66 times higher in the top risk group versus the lowest risk group, and the risk of metastatic disease was 4.18 times higher.

The data also revealed that men with African Ancestry had the highest risk of disease metastasis or death versus other ancestral populations.

“Compared to other tests of risk, the scoring algorithm uses nearly 300 variants linked to inherited genetic information, whereas some currently available commercial tests rely on expression of just a dozen or so cancer-related genes and a handful of reference genes,” lead study author Meghana Pagadala, VA Health Care System, La Jolla, California, and an MD/PhD candidate at the University of California, San Diego, stated in an ASCO news release. “One advantage to heritable genetic information is that is does not change through a person’s lifetime, whereas tumor gene expressions can be highly variable and are only available once a man has already developed the disease. This algorithm was developed to predict risk of prostate cancer at different ages.”

The study population was composed of 582,515 participants from the Million Veteran Program (MVP), a genomic database that accrues information from patients treated through the Veterans Administration Health Care System at 63 clinical locations nationwide. The median patient age in the study was 69 years.

When the researchers assessed ancestry and risk, the results showed that those with African ancestry had a 1.84 times greater risk of developing prostate cancer versus individuals of European ancestry. The risks of metastatic disease and death were 2.27 times and 1.97 times higher, respectively. Data for patients with Hispanic ancestry were similar to the European group. The study included individuals of Asian ancestry; however, this population was not big enough to adequately determine risk.

As would be expected, the PHS290 data showed that the risks of both developing prostate cancer and dying of the disease were higher among individuals with a family history of prostate cancer.

“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,” Pagadala, stated. “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.”

Also commenting on the study results in the news release, Robert Dreicer, MD, MS, MACP, FASCO, ASCO Expert in genitourinary cancers, stated, “Current prostate cancer screening recommendations rely on family history as well as race and ethnicity, factors which often 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 been validated in a diverse population.”

References

1. New Genetic Risk Score Stratifies Lifetime Risk of Dying of Prostate Cancer in Diverse Populations. Published online February 14, 2022. Accessed February 16, 2022. https://bit.ly/3JCL993

2. Pagadala M, Lynch JA, Karunamuni R, et al. Evaluating a polygenic hazard score to predict risk of developing metastatic or fatal prostate cancer in the multi-ancestry Million Veteran Program cohort. J Clin Oncol 40, 2022 (suppl 6; abstr 155). doi: 10.1200/JCO.2022.40.6_suppl.155