Shancheng Ren, Jianfeng Xu, and Tie Zhou contributed equally to this work.
Plateau effect of prostate cancer risk-associated SNPs in discriminating prostate biopsy outcomes
Article first published online: 26 AUG 2013
© 2013 Wiley Periodicals, Inc.
Volume 73, Issue 16, pages 1824–1835, December 2013
How to Cite
Ren, S., Xu, J., Zhou, T., Jiang, H., Chen, H., Liu, F., Na, R., Zhang, L., Wu, Y., Sun, J., Yang, B., Gao, X., Zheng, S. L., Xu, C., Ding, Q. and Sun, Y. (2013), Plateau effect of prostate cancer risk-associated SNPs in discriminating prostate biopsy outcomes. Prostate, 73: 1824–1835. doi: 10.1002/pros.22721
- Issue published online: 25 OCT 2013
- Article first published online: 26 AUG 2013
- Manuscript Accepted: 19 JUL 2013
- Manuscript Received: 18 JUN 2013
- National Science Foundation of China. Grant Number: 81101946
- Prostate Cancer Foundation Young Investigator Award
- Shanghai Pujiang Program. Grant Number: 12PJD008
- National Key Basic Research Program Grant 973. Grant Number: 2012CB518301
- Key Project of the National Natural Science Foundation of China. Grant Number: 81130047
- Fudan University “Thousand Talents Program”
- Huashan Hospital
- National Institutes of Health. Grant Number: NCI CA129684
- Science and Technology Commission of Shanghai Municipality. Grant Number: 11410708200
- The National Basic Research Program to Y.S. Grant Number: 2012CB518300
- genetic score;
Additional prostate cancer (PCa) risk-associated single nucleotide polymorphisms (SNPs) continue to be identified. It is unclear whether addition of newly identified SNPs improves the discriminative performance of biopsy outcomes over previously established SNPs.
A total of 667 consecutive patients that underwent prostate biopsy for detection of PCa at Huashan Hospital and Changhai Hospital, Shanghai, China were recruited. Genetic scores were calculated for each patient using various combinations of 29 PCa risk-associated SNPs. Performance of these genetic scores for discriminating prostate biopsy outcomes were compared using the area under a receiver operating characteristic curve (AUC).
The discriminative performance of genetic score derived from a panel of all 29 SNPs (24 previous and 5 new) was similar to that derived from the 24 previously established SNPs, the AUC of which were 0.60 and 0.61, respectively (P = 0.72). When SNPs with the strongest effect on PCa risk (ranked based on contribution to the total genetic variance from an external study) were sequentially added to the models for calculating genetic score, the AUC gradually increased and peaked at 0.62 with the top 13 strongest SNPs. Under the 13-SNP model, the PCa detection rate was 21.52%, 36.74%, and 51.98%, respectively for men with low (<0.5), intermediate (0.5–1.5), and high (>1.5) genetic score, P-trend = 9.91 × 10−6.
Genetic score based on PCa risk-associated SNPs implicated to date is a significant predictor of biopsy outcome. Additional small-effect PCa risk-associated SNPs to be discovered in the future are unlikely to further improve predictive performance. Prostate 73:1824–1835, 2013. © 2013 Wiley Periodicals, Inc.