Cabrera Serrano, Antonio JoséEspinet Solà, BlancaBlanco Ares, Gonzalo, 1989-Puiggros Metje, Anna MariaSainz, Juan2024-03-072024-03-072023Cabrera-Serrano AJ, Sánchez-Maldonado JM, Ter Horst R, Macauda A, García-Martín P, Benavente Y et al. Do gwas-identified risk variants for chronic lymphocytic leukemia influence overall patient survival and disease progression?. Int J Mol Sci. 2023 Apr 28;24(9):8005. DOI: 10.3390/ijms240980051422-0067http://hdl.handle.net/10230/59343Chronic 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.application/pdfeng© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).info:eu-repo/semantics/articlehttp://dx.doi.org/10.3390/ijms24098005TTFTChronic lymphocytic leukemiaGenetic variantsOverall survivalPolygenic risk scoreSusceptibilityinfo:eu-repo/semantics/openAccess