title: Plateau effect of prostate cancer risk-associated SNPs in discriminating prostate biopsy outcomes.
abstract: 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Shancheng
authors.initials: S
authors.lastname: Ren
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Xu
authors.forename: Tie
authors.initials: T
authors.lastname: Zhou
authors.forename: Haowen
authors.initials: H
authors.lastname: Jiang
authors.forename: Haitao
authors.initials: H
authors.lastname: Chen
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.forename: Rong
authors.initials: R
authors.lastname: Na
authors.forename: Limin
authors.initials: L
authors.lastname: Zhang
authors.forename: Yishuo
authors.initials: Y
authors.lastname: Wu
authors.forename: Jielin
authors.initials: J
authors.lastname: Sun
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.forename: Xu
authors.initials: X
authors.lastname: Gao
authors.forename: S Lilly
authors.initials: SL
authors.lastname: Zheng
authors.forename: Chuanliang
authors.initials: C
authors.lastname: Xu
authors.forename: Qiang
authors.initials: Q
authors.lastname: Ding
authors.forename: Yinghao
authors.initials: Y
authors.lastname: Sun
mesh_terms: D000368:Aged; D019540:Area Under Curve; D044466:Asian People / Q000235:genetics; D001706:Biopsy; D002681:China; D015331:Cohort Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology*; D012189:Retrospective Studies; D012307:Risk Factors
keywords: AUC; ChinaPCa; SNPs; biopsy; genetic score; prostate
references.citation: Asian J Androl. 2013 May;15(3):314-22
references.pmid: 23564047
references.citation: Nat Genet. 2010 Sep;42(9):751-4
references.pmid: 20676098
references.citation: Nat Genet. 2008 Mar;40(3):281-3
references.pmid: 18264098
references.citation: N Engl J Med. 2008 Jun 26;358(26):2796-803
references.pmid: 18579814
references.citation: Nat Genet. 2009 Oct;41(10):1055-7
references.pmid: 19767755
references.citation: N Engl J Med. 2012 Mar 15;366(11):981-90
references.pmid: 22417251
references.citation: J Urol. 2013 Aug;190(2):419-26
references.pmid: 23659877
references.citation: Eur Urol. 2012 Dec;62(6):953-61
references.pmid: 22652152
references.citation: Nat Genet. 2008 Mar;40(3):316-21
references.pmid: 18264097
references.citation: Nat Genet. 2012 Feb 26;44(4):426-9, S1
references.pmid: 22366784
references.citation: Biometrics. 1988 Sep;44(3):837-45
references.pmid: 3203132
references.citation: N Engl J Med. 2009 Mar 26;360(13):1310-9
references.pmid: 19297565
references.citation: PLoS One. 2012;7(10):e46454
references.pmid: 23071574
references.citation: Nat Genet. 2009 Oct;41(10):1058-60
references.pmid: 19767752
references.citation: Eur Urol. 2012 Mar;61(3):471-7
references.pmid: 22101116
references.citation: Prostate. 2009 Oct 1;69(14):1565-72
references.pmid: 19562736
references.citation: J Biopharm Stat. 2010 Mar;20(2):415-40
references.pmid: 20309766
references.citation: Nat Genet. 2009 Oct;41(10):1122-6
references.pmid: 19767754
references.citation: Nat Genet. 2008 Oct;40(10):1153-5
references.pmid: 18758462
references.citation: Hum Genet. 2011 Jun;129(6):687-94
references.pmid: 21465221
references.citation: Cancer Res. 2009 Apr 1;69(7):2720-3
references.pmid: 19318570
references.citation: Prostate. 2013 Nov;73(15):1651-9
references.pmid: 23868750
references.citation: J Natl Cancer Inst. 2006 Apr 19;98(8):529-34
references.pmid: 16622122
references.citation: N Engl J Med. 2009 Mar 26;360(13):1320-8
references.pmid: 19297566
references.citation: Eur Urol. 2013 Mar;63(3):585-7
references.pmid: 23245817
references.citation: Nat Genet. 2011 Jun;43(6):570-3
references.pmid: 21602798
references.citation: Nat Genet. 2007 May;39(5):631-7
references.pmid: 17401366
references.citation: Cancer. 2003 Apr 15;97(8):1894-903
references.pmid: 12673715
references.citation: Nat Genet. 2008 Mar;40(3):310-5
references.pmid: 18264096
references.citation: J Natl Cancer Inst. 2007 Dec 19;99(24):1836-44
references.pmid: 18073375
references.citation: Nat Genet. 2013 Apr;45(4):385-91, 391e1-2
references.pmid: 23535732
references.citation: N Engl J Med. 2008 Feb 28;358(9):910-9
references.pmid: 18199855
references.citation: Nat Genet. 2007 Aug;39(8):977-83
references.pmid: 17603485
references.citation: Cancer Epidemiol Biomarkers Prev. 2008 Aug;17(8):2052-61
references.pmid: 18708398
references.citation: Nat Genet. 2007 May;39(5):645-9
references.pmid: 17401363
references.citation: Nat Genet. 2012 Nov;44(11):1231-5
references.pmid: 23023329
references.citation: Int J Cancer. 2010 Dec 15;127(12):2893-917
references.pmid: 21351269
references.citation: Cancer Epidemiol Biomarkers Prev. 2009 Jun;18(6):1815-20
references.pmid: 19505914
references.citation: Genet Epidemiol. 2011 Sep;35(6):549-56
references.pmid: 21769933
references.citation: BJU Int. 2003 Jun;91(9):789-94
references.pmid: 12780833
references.citation: Prostate. 2012 Apr;72(5):577-83
references.pmid: 21796652
references.citation: Eur Urol. 2011 Jul;60(1):21-8
references.pmid: 21295399
references.citation: Prostate. 2013 Nov;73(15):1623-35
references.pmid: 24038036
references.citation: N Engl J Med. 2009 Apr 23;360(17):1701-3
references.pmid: 19369656
references.citation: Cancer Epidemiol Biomarkers Prev. 2012 Mar;21(3):437-44
references.pmid: 22237985
references.citation: Cancer Res. 2009 Jan 1;69(1):10-5
references.pmid: 19117981
references.citation: Nat Genet. 2009 Oct;41(10):1116-21
references.pmid: 19767753
references.citation: Int J Cancer. 2003 Dec 10;107(5):797-803
references.pmid: 14566830
references.citation: Hum Mol Genet. 2011 Oct 1;20(19):3867-75
references.pmid: 21743057
references.citation: Prostate. 2011 Mar 1;71(4):421-30
references.pmid: 20878950
references.citation: Nat Genet. 2006 Jun;38(6):652-8
references.pmid: 16682969
references.citation: Prostate. 2009 Mar 1;69(4):363-72
references.pmid: 19058137
references.citation: Ann Intern Med. 2008 Aug 5;149(3):185-91
references.pmid: 18678845