title: Human kallikrein-2 gene and protein expression predicts prostate cancer at repeat biopsy.
abstract: OBJECTIVE
  The human kallikrein-2 (hK2) protein and two single nucleotide polymorphism (SNPs) (rs2664155, rs198977) of the gene are associated with prostate cancer risk. We examined whether hK2 protein and gene SNPs predict prostate cancer at the time of repeat biopsy.
  
  
  METHODS
  We prospectively offered a repeat biopsy to men with a negative prostate biopsy performed for a PSA >4.0 ng/mL or abnormal Digital Rectal Exam (DRE) between 2001-2005. We genotyped and measured serum hK2 levels in 941 men who underwent a repeat prostate biopsy. Logistic regression analyses were conducted to determine the significance of KLK2 SNPs and hK2 levels for predicting cancer at repeat biopsy.
  
  
  RESULTS
  Of the 941 patients, 180 (19.1%) were found to have cancer. The rs198977 SNP was positively associated with cancer at repeat biopsy (OR variant T allele = 1.8, 95% CI: 1.04-3.13, p = 0.049). When combined, the odds ratio for prostate cancer for patients with high hK2 levels and the variant T-allele of rs198977 was 3.77 (95% CI: 1.94-7.32, p < 0.0001), compared to patients with low hK2 levels and the C-allele. The addition of hK2 levels and KLK2 rs198977 to the baseline predictive model did not significantly increase the area under the curve from a baseline model of 0.67 to 0.69 (p = 0.6).
  
  
  CONCLUSIONS
  The KLK2 SNP rs198977 was positively associated with hK2 levels and predicts prostate cancer at the time of repeat prostate biopsy. Further characterization of the KLK2 gene will be needed to determine its clinical utility.
authors.affiliation: Division of Urology, Sunnybrook Health Sciences Centre, Sunnybrook Research Institute, University of Toronto, 2075 Bayview Avenue, Suite MG-406, Toronto, ON M4N 3 M5 Canada.
authors.forename: Raj
authors.initials: R
authors.lastname: Satkunasivam
authors.affiliation: Division of Urology, Sunnybrook Health Sciences Centre, Sunnybrook Research Institute, University of Toronto, 2075 Bayview Avenue, Suite MG-406, Toronto, ON M4N 3 M5 Canada.
authors.forename: William
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Division of Urology, Princess Margaret Hospital, University of Toronto, Toronto, Ontario Canada.
authors.forename: John
authors.initials: J
authors.lastname: Trachtenberg
authors.affiliation: Department of Medical Imaging, Princess Margaret Hospital, University of Toronto, Toronto, Ontario Canada.
authors.forename: Ants
authors.initials: A
authors.lastname: Toi
authors.affiliation: Quantitative Health Sciences, The Cleveland Clinic, Cleveland, Ohio U.S.A.
authors.forename: Changhong
authors.initials: C
authors.lastname: Yu
authors.affiliation: Department of Biochemistry, Mount Sinai Hospital, University of Toronto, Toronto, Ontario Canada.
authors.forename: Eleftherios
authors.initials: E
authors.lastname: Diamandis
authors.affiliation: Quantitative Health Sciences, The Cleveland Clinic, Cleveland, Ohio U.S.A.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Kattan
authors.affiliation: Department of Public Health Sciences, Women's College Hospital, Women's College Research Institute, University of Toronto, Toronto, Ontario Canada.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Narod
authors.affiliation: Division of Urology, Sunnybrook Health Sciences Centre, Sunnybrook Research Institute, University of Toronto, 2075 Bayview Avenue, Suite MG-406, Toronto, ON M4N 3 M5 Canada.
authors.forename: Robert K
authors.initials: RK
authors.lastname: Nam
keywords: Human Kallikrein-2; Nomogram; Prostate cancer; Single nucleotide polymorphisms