Abstract
PurposeThe 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.MethodsWe 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.ResultsOf 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).ConclusionsThe 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.
Highlights
Transrectal ultrasound guided biopsy of the prostate is the gold standard to establish the diagnosis of prostate cancer among prescreened men
We showed that single nucleotide polymorphisms (SNPs) of the KLK2 gene, which encodes for the human kallikrein-2 (hK2) protein have been shown to be associated with prostate cancer (Nam et al 2003; Nam et al 2006; Nam et al 2009)
Serum hK2 levels were significantly higher among cases than controls, and the rs198977 KLK2 SNP was significantly associated with prostate cancer (Table 1)
Summary
Transrectal ultrasound guided biopsy of the prostate is the gold standard to establish the diagnosis of prostate cancer among prescreened men. We showed that single nucleotide polymorphisms (SNPs) of the KLK2 gene, which encodes for the hK2 protein have been shown to be associated with prostate cancer (Nam et al 2003; Nam et al 2006; Nam et al 2009). To examine whether these factors could be used to determine the presence of cancer among patients at the time of repeat biopsy after an initial negative biopsy, we conducted a prospective study among a cohort of men who had previously undergone biopsy with no evidence of prostate cancer. We conducted decision curve analysis to determine whether these factors related to hK2 provided additional predictive value compared to conventional risk factors
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