Predictive performance of prostate cancer risk in Chinese men using 33 reported prostate cancer risk-associated SNPs

Abstract

Background: Genome-wide association studies (GWAS) have identified more than 30 single nucleotide polymorphisms (SNPs) that were reproducibly associated with prostate cancer (PCa) risk in populations of European descent. In aggregate, these variants have shown potential to predict risk for PCa in European men. However, their utility for PCa risk prediction in Chinese men is unknown.

Methods: We selected 33 PCa risk-related SNPs that were originally identified in populations of European descent. Genetic scores were estimated for subjects in a Chinese case-control study (1,108 cases and 1,525 controls) based on these SNPs. To assess the performance of the genetic score on its ability to predict risk for PCa, we calculated area under the curve (AUC) of the receiver operating characteristic (ROC) in combination with 10-fold cross-validation.

Results: The genetic score was significantly higher for cases than controls (P = 5.91 × 10(-20)), and was significantly associated with risk of PCa in a dose-dependent manner (P for trend: 4.78 × 10(-18)). The AUC of the genetic score was 0.604 for risk prediction of PCa in Chinese men. When ORs derived from this Chinese study population were used to calculate genetic score, the AUCs were 0.631 for all 33 SNPs and 0.617 when using only the 11 significant SNPs.

Conclusion: Our results indicate that genetic variants related to PCa risk may be useful for risk prediction in Chinese men. Prospective studies are warranted to further evaluate these findings.

Figure 1

The distributions of prostate cancer cases and controls among different scales of genetic score

Figure 2

Receiver operating characteristic (ROC) curves for genetic models. The straight line indicates the null discrimination. Black curve shows the ROC based on the ORs of 33 SNPs from external meta-analysis in sutdies of European descent (CEU 33); Red curve shows the ROC based on the ORs of 33 SNPs in 1,108 cases and 1,525 controls in the current study (CHN 33); Blue curve shows the ROC based on the ORs of 11 significant SNPs in 1,108 cases and 1,525 controls in the current study (CHN 11). And the AUCs for CEU 33, CHN 33, and CHN 11 (0.604, 0.631 and 0.617, respectively) are presented in parentheses in the key.