Polygenic risk score improves prostate cancer risk prediction: results from the Stockholm-1 cohort study

Eur Urol. 2011 Jul;60(1):21-8. doi: 10.1016/j.eururo.2011.01.017. Epub 2011 Jan 18.

Abstract

Background: More than 1 million prostate biopsies are conducted yearly in the United States. The low specificity of prostate-specific antigen (PSA) results in diagnostic biopsies in men without prostate cancer (PCa). Additional information, such as genetic markers, could be used to avoid unnecessary biopsies.

Objective: To determine whether single nucleotide polymorphisms (SNPs) associated with PCa can be used to determine whether biopsy of the prostate is necessary.

Design, settings, and participants: The Stockholm-1 cohort (n = 5241) consisted of men who underwent a prostate biopsy during 2005 to 2007. PSA levels were retrieved from databases and family histories were obtained using a questionnaire. Thirty-five validated SNPs were analysed and converted into a genetic risk score that was implemented in a risk-prediction model.

Results and limitations: When comparing the nongenetic model (based on age, PSA, free-to-total PSA, and family history) with the genetic model and using a fixed number of detected PCa cases, it was found that the genetic model required significantly fewer biopsies than the nongenetic model, with 480 biopsies (22.7%) avoided, at a cost of missing a PCa diagnosis in 3% of patients characterised as having an aggressive disease. However, the overall genetic model does not discriminate between aggressive and nonaggressive cases.

Conclusion: Although the genetic model reduced the number of biopsies more than the nongenetic model, the clinical significance of this finding requires further evaluation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Cohort Studies
  • Humans
  • Male
  • Middle Aged
  • Multifactorial Inheritance
  • Polymorphism, Single Nucleotide
  • Prognosis
  • Prostatic Neoplasms / epidemiology*
  • Prostatic Neoplasms / genetics*
  • Risk Assessment
  • Sweden