TY  - JOUR
AU  - Cabrera-Serrano, Antonio José
AU  - Sánchez-Maldonado, José Manuel
AU  - Ter Horst, Rob
AU  - Macauda, Angelica
AU  - García-Martín, Paloma
AU  - Benavente, Yolanda
AU  - Landi, Stefano
AU  - Clay-Gilmour, Alyssa
AU  - Niazi, Yasmeen
AU  - Espinet, Blanca
AU  - Rodríguez-Sevilla, Juan José
AU  - Pérez, Eva María
AU  - Maffei, Rossana
AU  - Blanco, Gonzalo
AU  - Giaccherini, Matteo
AU  - Cerhan, James R
AU  - Marasca, Roberto
AU  - López-Nevot, Miguel Ángel
AU  - Chen-Liang, Tzu
AU  - Thomsen, Hauke
AU  - Gámez, Irene
AU  - Campa, Daniele
AU  - Moreno, Víctor
AU  - de Sanjosé, Silvia
AU  - Marcos-Gragera, Rafael
AU  - García-Álvarez, María
AU  - Dierssen-Sotos, Trinidad
AU  - Jerez, Andrés
AU  - Butrym, Aleksandra
AU  - Norman, Aaron D
AU  - Luppi, Mario
AU  - Slager, Susan L
AU  - Hemminki, Kari
AU  - Li, Yang
AU  - Berndt, Sonja I
AU  - Casabonne, Delphine
AU  - Alcoceba, Miguel
AU  - Puiggros, Anna
AU  - Netea, Mihai G
AU  - Försti, Asta
AU  - Canzian, Federico
AU  - Sainz, Juan
TI  - Do GWAS-Identified Risk Variants for Chronic Lymphocytic Leukemia Influence Overall Patient Survival and Disease Progression?
JO  - International journal of molecular sciences
VL  - 24
IS  - 9
SN  - 1422-0067
CY  - Basel
PB  - Molecular Diversity Preservation International
M1  - DKFZ-2023-00972
SP  - 8005
PY  - 2023
AB  - 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.
KW  - Adult
KW  - Humans
KW  - Leukemia, Lymphocytic, Chronic, B-Cell: genetics
KW  - Genome-Wide Association Study
KW  - Risk Factors
KW  - Disease Progression
KW  - Genetic Predisposition to Disease
KW  - Polymorphism, Single Nucleotide
KW  - TTFT (Other)
KW  - chronic lymphocytic leukemia (Other)
KW  - genetic variants (Other)
KW  - overall survival (Other)
KW  - polygenic risk score (Other)
KW  - susceptibility (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:37175717
C2  - pmc:PMC10178669
DO  - DOI:10.3390/ijms24098005
UR  - https://inrepo02.dkfz.de/record/276066
ER  -