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Prostate Cancer Analysis Explores Age-Related Risk Linked to Polygenic Risk Score

NEW YORK – The relative risk of developing prostate cancer associated with a polygenic risk score appears to be more pronounced for younger individuals than older ones with the same PRS, new research suggests, although their absolute risk stayed about the same.

"We found significantly greater relative risks for younger men (age 30-55 years) compared with older men (70-88 years)," first and corresponding author Daniel Schaid, a researcher at the Mayo Clinic in Rochester, and his colleagues wrote, even when calculating relative risk in two different ways.

As they reported in the American Journal of Human Genetics, the researchers used a weighted proportional hazards model to determine a prostate cancer PRS for 64,274 men with prostate cancer and 46,432 unaffected controls based on their genotyping profiles. Nearly 83 percent of the participants had European ancestry, they noted, while the remaining participants had African American, Latino, Asian, or Ghanaian ancestry.

"Polygenic risk scores (PRSs) for a variety of diseases have recently been shown to have relative risks that depend on age, and genetic relative risks decrease with increasing age," the authors explained. "A refined understanding of the age dependency of PRSs for a disease is important for personalized risk predictions and risk stratification."

The relative prostate cancer risk associated with a given polygenic score dipped in individuals over 55 years old, particularly in those of European ancestry, the team noted. The results suggested that an individual's age, population ancestry, and family history all come into play when interpreting the risk associated with the prostate cancer PRS.

Nevertheless, the investigators found that the absolute risk of developing prostate cancer, which also depends on the baseline incidence of the cancer at certain ages, did not stray significantly from the risk predictions made with the PRS approach, with or without taking age into account. This suggested that clinicians may not need to delve into the age-, population-, and family-related complications to relative risk when interpreting PRS results and sharing the information with patients in the clinic.

"[F]ollowing the recommendation to convey absolute risks to lay people in order to simplify interpretation of personal risks, we evaluated the impact of a PRS relative risk changing over ages on predicting the future absolute risk of prostate cancer," the authors explained, noting that "even though our results show strong evidence of relative risks due to PRS decreasing with increasing age, predicting future absolute risk while allowing for decreasing relative risk differed little from predictions that assumed a constant relative risk over ages."