%0 Journal Article
%A Huynh-Le, Minh-Phuong
%A Karunamuni, Roshan
%A Fan, Chun Chieh
%A Asona, Lui
%A Thompson, Wesley K
%A Martinez, Maria Elena
%A Eeles, Rosalind A
%A Kote-Jarai, Zsofia
%A Muir, Kenneth R
%A Lophatananon, Artitaya
%A Schleutker, Johanna
%A Pashayan, Nora
%A Batra, Jyotsna
%A Grönberg, Henrik
%A Neal, David E
%A Nordestgaard, Børge G
%A Tangen, Catherine M
%A MacInnis, Robert J
%A Wolk, Alicja
%A Albanes, Demetrius
%A Haiman, Christopher A
%A Travis, Ruth C
%A Blot, William J
%A Stanford, Janet L
%A Mucci, Lorelei A
%A West, Catharine M L
%A Nielsen, Sune F
%A Kibel, Adam S
%A Cussenot, Olivier
%A Berndt, Sonja I
%A Koutros, Stella
%A Sørensen, Karina Dalsgaard
%A Cybulski, Cezary
%A Grindedal, Eli Marie
%A Menegaux, Florence
%A Park, Jong Y
%A Ingles, Sue A
%A Maier, Christiane
%A Hamilton, Robert J
%A Rosenstein, Barry S
%A Lu, Yong-Jie
%A Watya, Stephen
%A Vega, Ana
%A Kogevinas, Manolis
%A Wiklund, Fredrik
%A Penney, Kathryn L
%A Huff, Chad D
%A Teixeira, Manuel R
%A Multigner, Luc
%A Leach, Robin J
%A Brenner, Hermann
%A John, Esther M
%A Kaneva, Radka
%A Logothetis, Christopher J
%A Neuhausen, Susan L
%A De Ruyck, Kim
%A Ost, Piet
%A Razack, Azad
%A Newcomb, Lisa F
%A Fowke, Jay H
%A Gamulin, Marija
%A Abraham, Aswin
%A Claessens, Frank
%A Castelao, Jose Esteban
%A Townsend, Paul A
%A Crawford, Dana C
%A Petrovics, Gyorgy
%A van Schaik, Ron H N
%A Parent, Marie-Élise
%A Hu, Jennifer J
%A Zheng, Wei
%A Committee, IMPACT Study Steering
%A Mills, Ian G
%A Andreassen, Ole A
%A Dale, Anders M
%A Seibert, Tyler M
%T Prostate cancer risk stratification improvement across multiple ancestries with new polygenic hazard score.
%J Prostate cancer and prostatic diseases
%V 25
%N 4
%@ 1365-7852
%C Basingstoke
%I Stockton Press
%M DKFZ-2022-00289
%P 755-761
%D 2022
%Z 2022 Apr;25(4):755-761
%X Prostate 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
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:35152271
%R 10.1038/s41391-022-00497-7
%U https://inrepo02.dkfz.de/record/178825