Genetic risk model could guide prostate cancer screening
medwireNews: A polygenic hazard score that evaluates an individual’s age-related risk for developing prostate cancer could help guide personalized decision making about prostate-specific antigen (PSA) screening, say researchers.
They analyzed data from a development cohort of 31,747 men enrolled in 21 studies of the PRACTICAL consortium to select 54 single nucleotide polymorphisms associated with a diagnosis of prostate cancer, and combined these with the individual’s genotype to generate the polygenic hazard score.
The score was a significant predictor of age at the onset of aggressive prostate cancer, defined as any neoplasm requiring treatment as per the US National Comprehensive Cancer Network guidelines (including Gleason score ≥7, stage T3–T4, PSA ≥10 ng/mL, or nodal or distant metastases). This was true for both the development cohort and the validation cohort, which comprised 6411 participants of the ProtecT trial.
Furthermore, men with a high polygenic hazard score (>98th centile) had a significant 2.9-fold increased risk for developing aggressive prostate cancer relative to those with an average score (30–70th centile).
The team notes in The BMJ that “[a]s the score is representative of a man’s fixed genetic risk, it can be calculated once, long before onset of [prostate cancer], and substantially inform the decision of whether he should undergo [prostate cancer] screening.”
However, Tyler Seibert (University of California, San Diego, La Jolla, USA) and collaborators point out that like other genetic prediction tools, the polygenic hazard score was not specific for aggressive prostate cancer alone, and significantly predicted the age of occurrence of both any prostate cancer and very aggressive prostate cancer (defined as any of Gleason score ≥8, stage T3–T4, or nodal or distant metastases).
Nonetheless they believe that the score could help to target screening efforts toward those men at highest risk for early-onset or aggressive prostate cancer needing treatment.
Interestingly, although screening decisions in the clinic are often based on a family history of prostate cancer, inclusion of this parameter did not improve the predictive ability of the polygenic hazard score for either aggressive or any prostate cancer in the validation set. But Seibert et al caution that this could be due to the relatively small size of the validation cohort.
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