Prediction of prostate cancer from prostate biopsy in Chinese men using a genetic score derived from 24 prostate cancer risk-associated SNPs

Abstract

Background: Twenty-four prostate cancer (PCa) risk-associated single nucleotide polymorphisms (SNPs) in Chinese men have been cataloged. We evaluated whether these SNPs can independently predict outcomes of prostate biopsy, and improve the predictive performance of existing clinical variables.

Methods: Three hundred eight consecutive patients that underwent prostate biopsy for detection of PCa at Huashan Hospital, Shanghai, China between April 2011 and August 2012 were recruited. Clinical variables such as serum prostate-specific antigen (PSA) levels and peripheral blood samples were collected prior to a 10-core biopsy. A genetic score based on these 24 PCa associated SNPs was calculated for each individual.

Results: Among 308 patients underwent prostate biopsy, 141 (45.8%) were diagnosed with PCa. Genetic score was significantly higher in patients with PCa (median = 1.30) than without (median = 0.89), P = 3.81 × 10(-6). The difference remained significant after adjusting for age and total PSA, P = 0.007. The PCa detection rate increased with increasing genetic score; 26.3%, 43.2%, and 60.0% for men with lower (<0.5), average (0.5-1.5), and higher (>1.5) genetic score, respectively, P(-trend) = 0.0003. For patients with moderately elevated PSA levels (1.6-20 ng/ml), the PCa detection rate was 31.2% overall and was 16.7%, 31.2%, and 40.9% for men with lower (<0.5), average (0.5-1.5), and higher (>1.5) genetic score, respectively, P(-trend) = 0.03. For patients with PSA ≥ 20 ng/ml, however, the PCa detection rates were high (>69%) regardless of genetic score.

Conclusion: A genetic score based on PCa risk-associated SNPs is an independent predictor of prostate biopsy outcomes in Chinese men and may be helpful to determine the need for prostate biopsy among patients within a "gray zone" of PCa risk.

Keywords: ChinaPCa; PSA; SNPs; risk assessment.

Fig. 1

Histogram (a) and box-plot (b) of genetic score derived from 24 known PCa risk-associated SNPs in patients with and without a diagnosis of prostate cancer.

Fig. 2

Prostate cancer detection rate among patients with low, average, andhigh genetic score.

Fig. 3

Prostate cancer detection rate among patients with various PSA levels and genetic score: (a) based on PSA levels, (b) based on genetic score among patients with moderately elevated PSA levels, and (c) based on genetic score among patients with greatly elevated PSA levels.

Fig. 4

Prostate cancer detection rate among patients with various risks for PCa defined by a comprehensive clinical model and genetic score: (a) based on estimated low or high risk for PCa, (b) based on genetic score among patients with low PCa risk, and (c) based on genetic score among patients with low PCa risk.