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@ARTICLE{HuynhLe:178825,
author = {M.-P. Huynh-Le and R. Karunamuni and C. C. Fan and L. Asona
and W. K. Thompson and M. E. Martinez and R. A. Eeles and Z.
Kote-Jarai and K. R. Muir and A. Lophatananon and J.
Schleutker and N. Pashayan and J. Batra and H. Grönberg and
D. E. Neal and B. G. Nordestgaard and C. M. Tangen and R. J.
MacInnis and A. Wolk and D. Albanes and C. A. Haiman and R.
C. Travis and W. J. Blot and J. L. Stanford and L. A. Mucci
and C. M. L. West and S. F. Nielsen and A. S. Kibel and O.
Cussenot and S. I. Berndt and S. Koutros and K. D. Sørensen
and C. Cybulski and E. M. Grindedal and F. Menegaux and J.
Y. Park and S. A. Ingles and C. Maier and R. J. Hamilton and
B. S. Rosenstein and Y.-J. Lu and S. Watya and A. Vega and
M. Kogevinas and F. Wiklund and K. L. Penney and C. D. Huff
and M. R. Teixeira and L. Multigner and R. J. Leach and H.
Brenner$^*$ and E. M. John and R. Kaneva and C. J.
Logothetis and S. L. Neuhausen and K. De Ruyck and P. Ost
and A. Razack and L. F. Newcomb and J. H. Fowke and M.
Gamulin and A. Abraham and F. Claessens and J. E. Castelao
and P. A. Townsend and D. C. Crawford and G. Petrovics and
R. H. N. van Schaik and M.-É. Parent and J. J. Hu and W.
Zheng and I. S. S. Committee and I. G. Mills and O. A.
Andreassen and A. M. Dale and T. M. Seibert},
collaboration = {UKGPCS collaborators and APCB and N. P. Investigators and
Collaborators and C. P. Investigators and P. S. S. Committee
and P. Consortium},
title = {{P}rostate cancer risk stratification improvement across
multiple ancestries with new polygenic hazard score.},
journal = {Prostate cancer and prostatic diseases},
volume = {25},
number = {4},
issn = {1365-7852},
address = {Basingstoke},
publisher = {Stockton Press},
reportid = {DKFZ-2022-00289},
pages = {755-761},
year = {2022},
note = {2022 Apr;25(4):755-761},
abstract = {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 $[95\%$ 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.},
cin = {C070 / HD01 / C120},
ddc = {610},
cid = {I:(DE-He78)C070-20160331 / I:(DE-He78)HD01-20160331 /
I:(DE-He78)C120-20160331},
pnm = {313 - Krebsrisikofaktoren und Prävention (POF4-313)},
pid = {G:(DE-HGF)POF4-313},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:35152271},
doi = {10.1038/s41391-022-00497-7},
url = {https://inrepo02.dkfz.de/record/178825},
}