@misc{10481/82716,
year = {2023},
month = {4},
url = {https://hdl.handle.net/10481/82716},
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},
organization = {Horizon 2020	856620},
organization = {Instituto de Salud Carlos III
Spanish Government},
organization = {Marie Curie Actions	PI17/02256
PI20/01845},
organization = {Consejeria de Transformacion Economica, Industria, Conocimiento y Universidades y FEDER	PY20/01282},
organization = {United States Department of Health & Human Services
National Institutes of Health (NIH) - USA
NIH National Cancer Institute (NCI)	P50 CA97274
R01 CA92153},
publisher = {MDPI},
keywords = {Chronic lymphocytic leukemia},
keywords = {Overall survival},
keywords = {Genetic variants},
keywords = {Susceptibility},
keywords = {Polygenic risk scoring},
title = {Do GWAS-Identified Risk Variants for Chronic Lymphocytic Leukemia Influence Overall Patient Survival and Disease Progression?},
doi = {10.3390/ijms24098005},
author = {Cabrera Serrano, Antonio José and Sáinz Pérez, Juan},
}