%0 Journal Article
%A Cabrera-Serrano, Antonio José
%A Sánchez-Maldonado, José Manuel
%A Ter Horst, Rob
%A Macauda, Angelica
%A García-Martín, Paloma
%A Benavente, Yolanda
%A Landi, Stefano
%A Clay-Gilmour, Alyssa
%A Niazi, Yasmeen
%A Espinet, Blanca
%A Rodríguez-Sevilla, Juan José
%A Pérez, Eva María
%A Maffei, Rossana
%A Blanco, Gonzalo
%A Giaccherini, Matteo
%A Cerhan, James R
%A Marasca, Roberto
%A López-Nevot, Miguel Ángel
%A Chen-Liang, Tzu
%A Thomsen, Hauke
%A Gámez, Irene
%A Campa, Daniele
%A Moreno, Víctor
%A de Sanjosé, Silvia
%A Marcos-Gragera, Rafael
%A García-Álvarez, María
%A Dierssen-Sotos, Trinidad
%A Jerez, Andrés
%A Butrym, Aleksandra
%A Norman, Aaron D
%A Luppi, Mario
%A Slager, Susan L
%A Hemminki, Kari
%A Li, Yang
%A Berndt, Sonja I
%A Casabonne, Delphine
%A Alcoceba, Miguel
%A Puiggros, Anna
%A Netea, Mihai G
%A Försti, Asta
%A Canzian, Federico
%A Sainz, Juan
%T Do GWAS-Identified Risk Variants for Chronic Lymphocytic Leukemia Influence Overall Patient Survival and Disease Progression?
%J International journal of molecular sciences
%V 24
%N 9
%@ 1422-0067
%C Basel
%I Molecular Diversity Preservation International
%M DKFZ-2023-00972
%P 8005
%D 2023
%X 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.
%K Adult
%K Humans
%K Leukemia, Lymphocytic, Chronic, B-Cell: genetics
%K Genome-Wide Association Study
%K Risk Factors
%K Disease Progression
%K Genetic Predisposition to Disease
%K Polymorphism, Single Nucleotide
%K TTFT (Other)
%K chronic lymphocytic leukemia (Other)
%K genetic variants (Other)
%K overall survival (Other)
%K polygenic risk score (Other)
%K susceptibility (Other)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:37175717
%2 pmc:PMC10178669
%R 10.3390/ijms24098005
%U https://inrepo02.dkfz.de/record/276066