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Plateau effect of prostate cancer risk‐associated SNPs in discriminating prostate biopsy outcomes
Author(s) -
Ren Shancheng,
Xu Jianfeng,
Zhou Tie,
Jiang Haowen,
Chen Haitao,
Liu Fang,
Na Rong,
Zhang Limin,
Wu Yishuo,
Sun Jielin,
Yang Bo,
Gao Xu,
Zheng S. Lilly,
Xu Chuanliang,
Ding Qiang,
Sun Yinghao
Publication year - 2013
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.22721
Subject(s) - single nucleotide polymorphism , prostate cancer , receiver operating characteristic , prostate biopsy , medicine , snp , biopsy , oncology , prostate , genotype , cancer , biology , genetics , gene
BACKGROUND 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. METHODS 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). RESULTS 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 . CONCLUSION 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.