Cabrera Serrano, Antonio JoséSánchez Maldonado, José ManuelTer Horst, RobMacauda, AngelicaGarcía Martín, PalomaBenavente, YolandaLandi, StefanoClay-Gilmour, AlyssaNiazi, YasmeenEspinet, BlancaRodríguez Sevilla, Juan JoséPérez, Eva MaríaMaffei, RossanaBlanco, GonzaloGiaccherini, MatteoCerhan, James R.Marasca, RobertoLópez Nevot, Miguel ÁngelChen Liang, TzuThomsen, HaukeGámez, IreneCampa, DanieleMoreno Aguado, VíctorSanjosé Llongueras, Silvia deMarcos Gragera, RafaelGarcía Álvarez, MaríaDierssen Sotos, TrinidadJerez, AndrésButrym, AleksandraNorman, Aaron D.Luppi, MarioSlager, Susan L.Hemminki, KariLi, YangBerndt, Sonja I.Casabonne, DelphineAlcoceba, MiguelPuiggròs Metje, Anna MariaNetea, Mihai G.Försti, AstaCanzian, FedericoSainz, Juan2023-07-192023-07-192023-04-281422-0067https://hdl.handle.net/2445/200907Chronic 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.11 p.application/pdfengcc by (c) Cabrera Serrano, Antonio José et al, 2023http://creativecommons.org/licenses/by/3.0/es/Leucèmia limfocítica crònicaGenèticaChronic lymphocytic leukemiaGeneticsinfo:eu-repo/semantics/article2023-06-22info:eu-repo/semantics/openAccess37175717