title: Association of prostate cancer risk alleles with unfavourable pathological characteristics in potential candidates for active surveillance.
abstract: OBJECTIVE
  • To assess whether the carrier status of 35 risk alleles for prostate cancer (CaP) is associated with having unfavourable pathological features in the radical prostatectomy specimen in men with clinically low risk CaP who fulfil commonly accepted criteria as candidates for active surveillance.
  
  
  METHODS
  • We studied men of European ancestry with CaP who fulfilled the commonly accepted clinical criteria for active surveillance (T1c, prostate-specific antigen <10 ng/mL, biopsy Gleason ≤6, three or fewer positive cores, ≤50% tumour involvement/core) but instead underwent early radical prostatectomy. • We genotyped these men for 35 CaP risk alleles. We defined 'unfavourable' pathological characteristics to be Gleason ≥7 and/or ≥ pT2b in their radical prostatectomy specimen.
  
  
  RESULTS
  • In all, 263 men (median age 60 [46-72] years) fulfilled our selection criteria for active surveillance, and 58 of 263 (22.1%) were found to have 'unfavourable' pathological characteristics. • The frequencies of three CaP risk alleles (rs1447295 [8q24], P= 0.004; rs1571801 [9q33.2], P= 0.03; rs11228565 [11q13], P= 0.02) were significantly higher in men with 'unfavourable' pathological characteristics. • Two other risk alleles were proportionately more frequent (rs10934853 [3q21], P= 0.06; rs1859962 [17q24], P= 0.07) but did not achieve nominal statistical significance. • Carriers of any one of the significantly over-represented risk alleles had twice the likelihood of unfavourable tumour features (P= 0.03), and carriers of any two had a sevenfold increased likelihood (P= 0.001). • Receiver-operator curve analysis demonstrated an area under the curve of 0.66, suggesting that the number of single nucleotide polymorphisms carried provided discrimination between men with 'favourable' and 'unfavourable' tumour features in their prostatectomy specimen.
  
  
  CONCLUSIONS
  • In potential candidates for active surveillance, certain CaP risk alleles are more prevalent in patients with 'unfavourable' pathological characteristics in their radical prostatectomy specimen.
authors.affiliation: Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Barry B
authors.initials: BB
authors.lastname: McGuire
authors.affiliation: Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Brian T
authors.initials: BT
authors.lastname: Helfand
authors.affiliation: Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Shilajit
authors.initials: S
authors.lastname: Kundu
authors.affiliation: Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Qiaoyan
authors.initials: Q
authors.lastname: Hu
authors.affiliation: Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Banks
authors.affiliation: Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Phillip
authors.initials: P
authors.lastname: Cooper
authors.affiliation: Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: William J
authors.initials: WJ
authors.lastname: Catalona
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D002877:Chromosomes, Human / Q000235:genetics; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D018579:Patient Selection; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000628:therapy; D012307:Risk Factors; D057832:Watchful Waiting
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