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000168960 1001_ $$00000-0001-8723-8123$$aKarunamuni, Roshan A$$b0
000168960 245__ $$aAdditional SNPs improve risk stratification of a polygenic hazard score for prostate cancer.
000168960 260__ $$aBasingstoke$$bStockton Press$$c2021
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000168960 520__ $$aPolygenic hazard scores (PHS) can identify individuals with increased risk of prostate cancer. We estimated the benefit of additional SNPs on performance of a previously validated PHS (PHS46).180 SNPs, shown to be previously associated with prostate cancer, were used to develop a PHS model in men with European ancestry. A machine-learning approach, LASSO-regularized Cox regression, was used to select SNPs and to estimate their coefficients in the training set (75,596 men). Performance of the resulting model was evaluated in the testing/validation set (6,411 men) with two metrics: (1) hazard ratios (HRs) and (2) positive predictive value (PPV) of prostate-specific antigen (PSA) testing. HRs were estimated between individuals with PHS in the top 5% to those in the middle 40% (HR95/50), top 20% to bottom 20% (HR80/20), and bottom 20% to middle 40% (HR20/50). PPV was calculated for the top 20% (PPV80) and top 5% (PPV95) of PHS as the fraction of individuals with elevated PSA that were diagnosed with clinically significant prostate cancer on biopsy.166 SNPs had non-zero coefficients in the Cox model (PHS166). All HR metrics showed significant improvements for PHS166 compared to PHS46: HR95/50 increased from 3.72 to 5.09, HR80/20 increased from 6.12 to 9.45, and HR20/50 decreased from 0.41 to 0.34. By contrast, no significant differences were observed in PPV of PSA testing for clinically significant prostate cancer.Incorporating 120 additional SNPs (PHS166 vs PHS46) significantly improved HRs for prostate cancer, while PPV of PSA testing remained the same.
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000168960 7001_ $$00000-0002-5025-4709$$aHuynh-Le, Minh-Phuong$$b1
000168960 7001_ $$aFan, Chun C$$b2
000168960 7001_ $$aThompson, Wesley$$b3
000168960 7001_ $$00000-0002-3698-6241$$aEeles, Rosalind A$$b4
000168960 7001_ $$aKote-Jarai, Zsofia$$b5
000168960 7001_ $$00000-0001-6429-988X$$aMuir, Kenneth$$b6
000168960 7001_ $$aLophatananon, Artitaya$$b7
000168960 7001_ $$aUKGPCS collaborators$$b8$$eCollaboration Author
000168960 7001_ $$00000-0002-1863-0305$$aSchleutker, Johanna$$b9
000168960 7001_ $$aPashayan, Nora$$b10
000168960 7001_ $$00000-0003-4646-6247$$aBatra, Jyotsna$$b11
000168960 7001_ $$aBioResource, APCB$$b12$$eCollaboration Author
000168960 7001_ $$aGrönberg, Henrik$$b13
000168960 7001_ $$aWalsh, Eleanor I$$b14
000168960 7001_ $$aTurner, Emma L$$b15
000168960 7001_ $$aLane, Athene$$b16
000168960 7001_ $$00000-0002-7992-7719$$aMartin, Richard M$$b17
000168960 7001_ $$aNeal, David E$$b18
000168960 7001_ $$aDonovan, Jenny L$$b19
000168960 7001_ $$aHamdy, Freddie C$$b20
000168960 7001_ $$aNordestgaard, Børge G$$b21
000168960 7001_ $$aTangen, Catherine M$$b22
000168960 7001_ $$aMacInnis, Robert J$$b23
000168960 7001_ $$aWolk, Alicja$$b24
000168960 7001_ $$aAlbanes, Demetrius$$b25
000168960 7001_ $$aHaiman, Christopher A$$b26
000168960 7001_ $$aTravis, Ruth C$$b27
000168960 7001_ $$aStanford, Janet L$$b28
000168960 7001_ $$aMucci, Lorelei A$$b29
000168960 7001_ $$aWest, Catharine M L$$b30
000168960 7001_ $$aNielsen, Sune F$$b31
000168960 7001_ $$aKibel, Adam S$$b32
000168960 7001_ $$00000-0002-4623-0544$$aWiklund, Fredrik$$b33
000168960 7001_ $$aCussenot, Olivier$$b34
000168960 7001_ $$aBerndt, Sonja I$$b35
000168960 7001_ $$aKoutros, Stella$$b36
000168960 7001_ $$00000-0002-4902-5490$$aSørensen, Karina Dalsgaard$$b37
000168960 7001_ $$aCybulski, Cezary$$b38
000168960 7001_ $$aGrindedal, Eli Marie$$b39
000168960 7001_ $$aPark, Jong Y$$b40
000168960 7001_ $$aIngles, Sue A$$b41
000168960 7001_ $$aMaier, Christiane$$b42
000168960 7001_ $$aHamilton, Robert J$$b43
000168960 7001_ $$aRosenstein, Barry S$$b44
000168960 7001_ $$aVega, Ana$$b45
000168960 7001_ $$aCommittee, IMPACT Study Steering$$b46
000168960 7001_ $$aCollaborators$$b47$$eCollaboration Author
000168960 7001_ $$aKogevinas, Manolis$$b48
000168960 7001_ $$aPenney, Kathryn L$$b49
000168960 7001_ $$00000-0002-4896-5982$$aTeixeira, Manuel R$$b50
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000168960 7001_ $$aJohn, Esther M$$b52
000168960 7001_ $$aKaneva, Radka$$b53
000168960 7001_ $$aLogothetis, Christopher J$$b54
000168960 7001_ $$aNeuhausen, Susan L$$b55
000168960 7001_ $$aRazack, Azad$$b56
000168960 7001_ $$aNewcomb, Lisa F$$b57
000168960 7001_ $$aInvestigators, Canary PASS$$b58$$eCollaboration Author
000168960 7001_ $$00000-0003-2431-7910$$aGamulin, Marija$$b59
000168960 7001_ $$aUsmani, Nawaid$$b60
000168960 7001_ $$aClaessens, Frank$$b61
000168960 7001_ $$aGago-Dominguez, Manuela$$b62
000168960 7001_ $$aTownsend, Paul A$$b63
000168960 7001_ $$00000-0001-6967-1708$$aRoobol, Monique J$$b64
000168960 7001_ $$aZheng, Wei$$b65
000168960 7001_ $$aCommittee, Profile Study Steering$$b66$$eCollaboration Author
000168960 7001_ $$aMills, Ian G$$b67
000168960 7001_ $$00000-0002-4461-3568$$aAndreassen, Ole A$$b68
000168960 7001_ $$aDale, Anders M$$b69
000168960 7001_ $$00000-0002-4089-7399$$aSeibert, Tyler M$$b70
000168960 7001_ $$aConsortium, PRACTICAL$$b71$$eCollaboration Author
000168960 773__ $$0PERI:(DE-600)2008886-3$$a10.1038/s41391-020-00311-2$$gVol. 24, no. 2, p. 532 - 541$$n2$$p532 - 541$$tProstate cancer and prostatic diseases$$v24$$x1476-5608$$y2021
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