Do GWAS-Identified Risk Variants for Chronic Lymphocytic Leukemia Influence Overall Patient Survival and Disease Progression?

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 pa...

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Detalles Bibliográficos
Autores: Cabrera Serrano, Antonio José, Sánchez Maldonado, José Manuel, Ter Horst, Rob, Macauda, Angelica, García Martín, Paloma, Benavente, Yolanda, Landi, Stefano, Clay-Gilmour, Alyssa, Niazi, Yasmeen, Espinet, Blanca, Rodríguez Sevilla, Juan José, Pérez, Eva María, Maffei, Rossana, Blanco, Gonzalo, Giaccherini, Matteo, Cerhan, James R., Marasca, Roberto, López Nevot, Miguel Ángel, Chen Liang, Tzu, Thomsen, Hauke, Gámez, Irene, Campa, Daniele, Moreno Aguado, Víctor, Sanjosé Llongueras, Silvia de, Marcos Gragera, Rafael, García Álvarez, María, Dierssen Sotos, Trinidad, Jerez, Andrés, Butrym, Aleksandra, Norman, Aaron D., Luppi, Mario, Slager, Susan L., Hemminki, Kari, Li, Yang, Berndt, Sonja I., Casabonne, Delphine, Alcoceba, Miguel, Puiggròs Metje, Anna Maria, Netea, Mihai G., Försti, Asta, Canzian, Federico, Sainz, Juan
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/200907
Acceso en línea:https://hdl.handle.net/2445/200907
Access Level:acceso abierto
Palabra clave:Leucèmia limfocítica crònica
Genètica
Chronic lymphocytic leukemia
Genetics
Descripción
Sumario: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.

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