title: Polygenic risk score improves prostate cancer risk prediction: results from the Stockholm-1 cohort study.
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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
  
  
  CONCLUSIONS
  Although the genetic model reduced the number of biopsies more than the nongenetic model, the clinical significance of this finding requires further evaluation.
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
authors.forename: Markus
authors.initials: M
authors.lastname: Aly
authors.forename: Fredrik
authors.initials: F
authors.lastname: Wiklund
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Xu
authors.forename: William B
authors.initials: WB
authors.lastname: Isaacs
authors.forename: Martin
authors.initials: M
authors.lastname: Eklund
authors.forename: Mauro
authors.initials: M
authors.lastname: D'Amato
authors.forename: Jan
authors.initials: J
authors.lastname: Adolfsson
authors.forename: Henrik
authors.initials: H
authors.lastname: Grönberg
mesh_terms: D000368:Aged; D015331:Cohort Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D020412:Multifactorial Inheritance; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D018570:Risk Assessment; D013548:Sweden