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@ARTICLE{CabreraSerrano:276066,
author = {A. J. Cabrera-Serrano and J. M. Sánchez-Maldonado and R.
Ter Horst and A. Macauda$^*$ and P. García-Martín and Y.
Benavente and S. Landi and A. Clay-Gilmour and Y. Niazi$^*$
and B. Espinet and J. J. Rodríguez-Sevilla and E. M. Pérez
and R. Maffei and G. Blanco and M. Giaccherini and J. R.
Cerhan and R. Marasca and M. Á. López-Nevot and T.
Chen-Liang and H. Thomsen and I. Gámez and D. Campa and V.
Moreno and S. de Sanjosé and R. Marcos-Gragera and M.
García-Álvarez and T. Dierssen-Sotos and A. Jerez and A.
Butrym and A. D. Norman and M. Luppi and S. L. Slager and K.
Hemminki$^*$ and Y. Li and S. I. Berndt and D. Casabonne and
M. Alcoceba and A. Puiggros and M. G. Netea and A.
Försti$^*$ and F. Canzian$^*$ and J. Sainz},
title = {{D}o {GWAS}-{I}dentified {R}isk {V}ariants for {C}hronic
{L}ymphocytic {L}eukemia {I}nfluence {O}verall {P}atient
{S}urvival and {D}isease {P}rogression?},
journal = {International journal of molecular sciences},
volume = {24},
number = {9},
issn = {1422-0067},
address = {Basel},
publisher = {Molecular Diversity Preservation International},
reportid = {DKFZ-2023-00972},
pages = {8005},
year = {2023},
abstract = {Chronic lymphocytic leukemia (CLL) is the most common
leukemia among adults worldwide. Although genome-wide
association studies (GWAS) have uncovered the germline
genetic component underlying CLL susceptibility, the
potential use of GWAS-identified risk variants to predict
disease progression and patient survival remains unexplored.
Here, we evaluated whether 41 GWAS-identified risk variants
for CLL could influence overall survival (OS) and disease
progression, defined as time to first treatment (TTFT) in a
cohort of 1039 CLL cases ascertained through the CRuCIAL
consortium. Although this is the largest study assessing the
effect of GWAS-identified susceptibility variants for CLL on
OS, we only found a weak association of ten single
nucleotide polymorphisms (SNPs) with OS (p < 0.05) that did
not remain significant after correction for multiple
testing. In line with these results, polygenic risk scores
(PRSs) built with these SNPs in the CRuCIAL cohort showed a
modest association with OS and a low capacity to predict
patient survival, with an area under the receiver operating
characteristic curve (AUROC) of 0.57. Similarly, seven SNPs
were associated with TTFT (p < 0.05); however, these did not
reach the multiple testing significance threshold, and the
meta-analysis with previous published data did not confirm
any of the associations. As expected, PRSs built with these
SNPs showed reduced accuracy in prediction of disease
progression (AUROC = 0.62). These results suggest that
susceptibility variants for CLL do not impact overall
survival and disease progression in CLL patients.},
keywords = {Adult / Humans / Leukemia, Lymphocytic, Chronic, B-Cell:
genetics / Genome-Wide Association Study / Risk Factors /
Disease Progression / Genetic Predisposition to Disease /
Polymorphism, Single Nucleotide / TTFT (Other) / chronic
lymphocytic leukemia (Other) / genetic variants (Other) /
overall survival (Other) / polygenic risk score (Other) /
susceptibility (Other)},
cin = {C055 / B062 / HD01 / C020},
ddc = {540},
cid = {I:(DE-He78)C055-20160331 / I:(DE-He78)B062-20160331 /
I:(DE-He78)HD01-20160331 / I:(DE-He78)C020-20160331},
pnm = {313 - Krebsrisikofaktoren und Prävention (POF4-313)},
pid = {G:(DE-HGF)POF4-313},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:37175717},
pmc = {pmc:PMC10178669},
doi = {10.3390/ijms24098005},
url = {https://inrepo02.dkfz.de/record/276066},
}