TY  - JOUR
AU  - Huynh-Le, Minh-Phuong
AU  - Karunamuni, Roshan
AU  - Fan, Chun Chieh
AU  - Asona, Lui
AU  - Thompson, Wesley K
AU  - Martinez, Maria Elena
AU  - Eeles, Rosalind A
AU  - Kote-Jarai, Zsofia
AU  - Muir, Kenneth R
AU  - Lophatananon, Artitaya
AU  - Schleutker, Johanna
AU  - Pashayan, Nora
AU  - Batra, Jyotsna
AU  - Grönberg, Henrik
AU  - Neal, David E
AU  - Nordestgaard, Børge G
AU  - Tangen, Catherine M
AU  - MacInnis, Robert J
AU  - Wolk, Alicja
AU  - Albanes, Demetrius
AU  - Haiman, Christopher A
AU  - Travis, Ruth C
AU  - Blot, William J
AU  - Stanford, Janet L
AU  - Mucci, Lorelei A
AU  - West, Catharine M L
AU  - Nielsen, Sune F
AU  - Kibel, Adam S
AU  - Cussenot, Olivier
AU  - Berndt, Sonja I
AU  - Koutros, Stella
AU  - Sørensen, Karina Dalsgaard
AU  - Cybulski, Cezary
AU  - Grindedal, Eli Marie
AU  - Menegaux, Florence
AU  - Park, Jong Y
AU  - Ingles, Sue A
AU  - Maier, Christiane
AU  - Hamilton, Robert J
AU  - Rosenstein, Barry S
AU  - Lu, Yong-Jie
AU  - Watya, Stephen
AU  - Vega, Ana
AU  - Kogevinas, Manolis
AU  - Wiklund, Fredrik
AU  - Penney, Kathryn L
AU  - Huff, Chad D
AU  - Teixeira, Manuel R
AU  - Multigner, Luc
AU  - Leach, Robin J
AU  - Brenner, Hermann
AU  - John, Esther M
AU  - Kaneva, Radka
AU  - Logothetis, Christopher J
AU  - Neuhausen, Susan L
AU  - De Ruyck, Kim
AU  - Ost, Piet
AU  - Razack, Azad
AU  - Newcomb, Lisa F
AU  - Fowke, Jay H
AU  - Gamulin, Marija
AU  - Abraham, Aswin
AU  - Claessens, Frank
AU  - Castelao, Jose Esteban
AU  - Townsend, Paul A
AU  - Crawford, Dana C
AU  - Petrovics, Gyorgy
AU  - van Schaik, Ron H N
AU  - Parent, Marie-Élise
AU  - Hu, Jennifer J
AU  - Zheng, Wei
AU  - Committee, IMPACT Study Steering
AU  - Mills, Ian G
AU  - Andreassen, Ole A
AU  - Dale, Anders M
AU  - Seibert, Tyler M
TI  - Prostate cancer risk stratification improvement across multiple ancestries with new polygenic hazard score.
JO  - Prostate cancer and prostatic diseases
VL  - 25
IS  - 4
SN  - 1365-7852
CY  - Basingstoke
PB  - Stockton Press
M1  - DKFZ-2022-00289
SP  - 755-761
PY  - 2022
N1  - 2022 Apr;25(4):755-761
AB  - 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
LB  - PUB:(DE-HGF)16
C6  - pmid:35152271
DO  - DOI:10.1038/s41391-022-00497-7
UR  - https://inrepo02.dkfz.de/record/178825
ER  -