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000178825 1001_ $$00000-0002-5025-4709$$aHuynh-Le, Minh-Phuong$$b0
000178825 245__ $$aProstate cancer risk stratification improvement across multiple ancestries with new polygenic hazard score.
000178825 260__ $$aBasingstoke$$bStockton Press$$c2022
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000178825 500__ $$a2022 Apr;25(4):755-761
000178825 520__ $$aProstate cancer risk stratification using single-nucleotide polymorphisms (SNPs) demonstrates considerable promise in men of European, Asian, and African genetic ancestries, but there is still need for increased accuracy. We evaluated whether including additional SNPs in a prostate cancer polygenic hazard score (PHS) would improve associations with clinically significant prostate cancer in multi-ancestry datasets.In total, 299 SNPs previously associated with prostate cancer were evaluated for inclusion in a new PHS, using a LASSO-regularized Cox proportional hazards model in a training dataset of 72,181 men from the PRACTICAL Consortium. The PHS model was evaluated in four testing datasets: African ancestry, Asian ancestry, and two of European Ancestry-the Cohort of Swedish Men (COSM) and the ProtecT study. Hazard ratios (HRs) were estimated to compare men with high versus low PHS for association with clinically significant, with any, and with fatal prostate cancer. The impact of genetic risk stratification on the positive predictive value (PPV) of PSA testing for clinically significant prostate cancer was also measured.The final model (PHS290) had 290 SNPs with non-zero coefficients. Comparing, for example, the highest and lowest quintiles of PHS290, the hazard ratios (HRs) for clinically significant prostate cancer were 13.73 [95% CI: 12.43-15.16] in ProtecT, 7.07 [6.58-7.60] in African ancestry, 10.31 [9.58-11.11] in Asian ancestry, and 11.18 [10.34-12.09] in COSM. Similar results were seen for association with any and fatal prostate cancer. Without PHS stratification, the PPV of PSA testing for clinically significant prostate cancer in ProtecT was 0.12 (0.11-0.14). For the top 20% and top 5% of PHS290, the PPV of PSA testing was 0.19 (0.15-0.22) and 0.26 (0.19-0.33), respectively.We demonstrate better genetic risk stratification for clinically significant prostate cancer than prior versions of PHS in multi-ancestry datasets. This is promising for implementing precision-medicine approaches to prostate cancer screening decisions in diverse populations.
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000178825 7001_ $$aKarunamuni, Roshan$$b1
000178825 7001_ $$00000-0001-9437-2128$$aFan, Chun Chieh$$b2
000178825 7001_ $$00000-0002-0076-3492$$aAsona, Lui$$b3
000178825 7001_ $$aThompson, Wesley K$$b4
000178825 7001_ $$aMartinez, Maria Elena$$b5
000178825 7001_ $$00000-0002-3698-6241$$aEeles, Rosalind A$$b6
000178825 7001_ $$aKote-Jarai, Zsofia$$b7
000178825 7001_ $$00000-0001-6429-988X$$aMuir, Kenneth R$$b8
000178825 7001_ $$aLophatananon, Artitaya$$b9
000178825 7001_ $$00000-0002-1863-0305$$aSchleutker, Johanna$$b10
000178825 7001_ $$00000-0003-0843-2468$$aPashayan, Nora$$b11
000178825 7001_ $$00000-0003-4646-6247$$aBatra, Jyotsna$$b12
000178825 7001_ $$00000-0002-1073-2753$$aGrönberg, Henrik$$b13
000178825 7001_ $$aNeal, David E$$b14
000178825 7001_ $$00000-0002-1954-7220$$aNordestgaard, Børge G$$b15
000178825 7001_ $$aTangen, Catherine M$$b16
000178825 7001_ $$aMacInnis, Robert J$$b17
000178825 7001_ $$00000-0001-7387-6845$$aWolk, Alicja$$b18
000178825 7001_ $$aAlbanes, Demetrius$$b19
000178825 7001_ $$aHaiman, Christopher A$$b20
000178825 7001_ $$00000-0002-9571-0763$$aTravis, Ruth C$$b21
000178825 7001_ $$aBlot, William J$$b22
000178825 7001_ $$aStanford, Janet L$$b23
000178825 7001_ $$aMucci, Lorelei A$$b24
000178825 7001_ $$00000-0002-0839-3449$$aWest, Catharine M L$$b25
000178825 7001_ $$aNielsen, Sune F$$b26
000178825 7001_ $$aKibel, Adam S$$b27
000178825 7001_ $$aCussenot, Olivier$$b28
000178825 7001_ $$aBerndt, Sonja I$$b29
000178825 7001_ $$aKoutros, Stella$$b30
000178825 7001_ $$00000-0002-4902-5490$$aSørensen, Karina Dalsgaard$$b31
000178825 7001_ $$aCybulski, Cezary$$b32
000178825 7001_ $$aGrindedal, Eli Marie$$b33
000178825 7001_ $$00000-0003-3363-6411$$aMenegaux, Florence$$b34
000178825 7001_ $$aPark, Jong Y$$b35
000178825 7001_ $$aIngles, Sue A$$b36
000178825 7001_ $$aMaier, Christiane$$b37
000178825 7001_ $$aHamilton, Robert J$$b38
000178825 7001_ $$aRosenstein, Barry S$$b39
000178825 7001_ $$00000-0001-6174-6621$$aLu, Yong-Jie$$b40
000178825 7001_ $$aWatya, Stephen$$b41
000178825 7001_ $$00000-0002-7416-5137$$aVega, Ana$$b42
000178825 7001_ $$00000-0002-9605-0461$$aKogevinas, Manolis$$b43
000178825 7001_ $$00000-0002-4623-0544$$aWiklund, Fredrik$$b44
000178825 7001_ $$aPenney, Kathryn L$$b45
000178825 7001_ $$aHuff, Chad D$$b46
000178825 7001_ $$00000-0002-4896-5982$$aTeixeira, Manuel R$$b47
000178825 7001_ $$00000-0003-3205-8568$$aMultigner, Luc$$b48
000178825 7001_ $$aLeach, Robin J$$b49
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000178825 7001_ $$aJohn, Esther M$$b51
000178825 7001_ $$aKaneva, Radka$$b52
000178825 7001_ $$aLogothetis, Christopher J$$b53
000178825 7001_ $$aNeuhausen, Susan L$$b54
000178825 7001_ $$aDe Ruyck, Kim$$b55
000178825 7001_ $$00000-0002-2203-4848$$aOst, Piet$$b56
000178825 7001_ $$aRazack, Azad$$b57
000178825 7001_ $$aNewcomb, Lisa F$$b58
000178825 7001_ $$00000-0003-3803-8162$$aFowke, Jay H$$b59
000178825 7001_ $$00000-0003-2431-7910$$aGamulin, Marija$$b60
000178825 7001_ $$00000-0003-0024-3339$$aAbraham, Aswin$$b61
000178825 7001_ $$aClaessens, Frank$$b62
000178825 7001_ $$aCastelao, Jose Esteban$$b63
000178825 7001_ $$aTownsend, Paul A$$b64
000178825 7001_ $$00000-0002-6437-6248$$aCrawford, Dana C$$b65
000178825 7001_ $$00000-0003-3732-284X$$aPetrovics, Gyorgy$$b66
000178825 7001_ $$avan Schaik, Ron H N$$b67
000178825 7001_ $$00000-0002-4196-3773$$aParent, Marie-Élise$$b68
000178825 7001_ $$aHu, Jennifer J$$b69
000178825 7001_ $$00000-0003-1226-070X$$aZheng, Wei$$b70
000178825 7001_ $$aUKGPCS collaborators$$b71$$eCollaboration Author
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000178825 7001_ $$aMills, Ian G$$b79
000178825 7001_ $$aAndreassen, Ole A$$b80
000178825 7001_ $$aDale, Anders M$$b81
000178825 7001_ $$00000-0002-4089-7399$$aSeibert, Tyler M$$b82
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