Prostate cancer antigen 3 and genetic risk score as markers for the detection of prostate cancer in the Chinese population

collected for each patient before biopsy. The study was approved by the Institutional Ethics Review Board at Huashan Hospital and written informed consent was completed for each patient. Because the Hologic PCA3 kit is not currently available in China, urine PCA3 RNA level was measured using an in-house qPCR method and its level was normalized by urine levels of PSA mRNA. PCA3 level was calculated using ∆Ct = Ct PCA3 − Ct PSA. 8 Twenty-nine PCa risk-associated SNPs discovered from GWAS and confirmed in the Chinese population (P < 0.05) were genotyped using MassARRAY A GRS was calculated for each subject based on their genotypes at these 29 SNPs and weighted by odd ratios of these SNPs derived from an external study. 10 Association of PCa diagnosis with PCA3, GRS, and other clinical variables were tested using both univariate and multivariate analyses. Total PSA, PCA3, free to total PSA ratio, and GRS were log-transformed prior to statistical tests. The key demographic and clinical variables for the 99 patients in the cohort, as well as their association with PCa risk, are presented in Table 1. Based on univariate analysis, higher PCA3 (P = 0.0002), higher total PSA (P = 0.0002), higher GRS (P = 0.0008), lower free to total PSA ratio (P = 0.007), and smaller prostate volume (P = 0.0003) were each associated with increased risk for PCa. The performance for discriminating PCa from non-PCa, measured by area under the curve (AUC), was 0.73 for total PSA, 0.77 for PCA3, and 0.70 for GRS. We also examined in detail the added value of PCA3 and GRS to total PSA in discriminating prostate biopsy outcomes (Table 2). Compared to Model 1 with total PSA alone where AUC was 0.73, the AUC increased to 0.81 for Model 2 with total PSA and GRS (P = 0.05), and to 0.84 for Model 3 with total PSA and PCA3 (P = 0.01). The AUC for Model 4 with all three variables (total PSA, GRS and PCA3) was further increased to 0.86, although the improvement was not statistically significant over Model 2 (P = 0.08) or Model 3 (P = 0.34). When all six variables were considered together in a multivariate analysis, only three variables were independently associated with PCa risk from a multivariate analysis; total PSA (P = 0.001), prostate volume (P = 0.0001), and PCA3 (P = 0.027). The AUC of the best …