Polygenic risk score and family history independently predict prostate cancer

  • Na R & al.
  • JAMA Netw Open
  • 2 Dec 2019

  • curated by Deepa Koli
  • Univadis Clinical Summaries
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Takeaway

  • Higher genetic risk score (GRS) and positive family history are associated with significant risk for prostate cancer (PCa).

Why this matters

  • Combining family history and GRS can improve patient stratification and screening strategies.

Study design

  • Secondary analysis of 3225 men (aged 50-75 years) from randomized, double-blind, placebo-controlled, 4-year REDUCE trial.
  • The GRS was calculated using established PCa risk-associated single nucleotide polymorphisms.
  • Funding: National Cancer Institute.

Key results

  • PCa detection rate by GRS risk group:
    • 14%, 22%, and 32% in low-, average-, and high-GRS risk groups, respectively (P-trend<.001>
  • PCa detection rate was 27% in men with family history vs 21% in those without (P=.02).
  • PCa diagnosis-free survival (PDFS) was worse in:
    • Men in the higher GRS risk group (χ2=53.3; P-trend<.001>
    • Men with family history of PCa vs no history (73 vs 77 years; χ2=0.59; P<.001>
  • PDFS was significantly worse in men with higher GRS risk groups or family history (χ2=63.0; log-rank P<.001>
  • GRS (β=0.28; P<.001 and family history p showed an independent association with pdfs no interaction was observed between them>2=0.19; P=.91).

Limitations

  • May not be generalizable to non-European men.