Do GWAS-Identified Risk Variants for Chronic Lymphocytic Leukemia Influence Overall Patient Survival and Disease Progression?
Year: 2023
Type: article
Study design: Observational Study
Abstract: 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.
DOI: 10.3390/ijms24098005
Authors: Antonio José Cabrera-Serrano, José Manuel Sánchez-Maldonado, Rob ter Horst, Angelica Macauda, Paloma García-Martín, Yolanda Benavente, Stefano Landi, Alyssa Clay-Gilmour, Yasmeen Niazi, Blanca Espinet, Juan José Rodríguez-Sevilla, Eva María Pérez, Rossana Maffei, Gonzalo Blanco, Matteo Giaccherini, James R. Cerhan, Roberto Marasca, Miguel Ángel López-Nevot, Tzu Chen-Liang, Hauke Thomsen, Irene Gámez, Daniele Campa, Víctor Moreno, Silvia de Sanjosé, Rafael Marcos-Gragera, María García-Álvarez, Trinidad Dierssen-Sotos, Andrés Jerez, Aleksandra Butrym, Aaron D. Norman, Mario Luppi, Susan L. Slager, Kari Hemminki, Yang Li, Sonja I. Berndt, Delphine Casabonne, Miguel Alcoceba, Anna Puiggros, Mihai G. Netea, Asta Försti, Federico Canzian, Juan Sainz
Institutions: Universidad de Granada, Instituto de Investigación Biosanitaria de Granada, Pfizer-University of Granada-Junta de Andalucía Centre for Genomics and Oncological Research, Austrian Academy of Sciences, CeMM Research Center for Molecular Medicine, German Cancer Research Center, Institut d'Investigació Biomédica de Bellvitge, Institut Català d'Oncologia, Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública, Universitat de Barcelona, University of Pisa, University of South Carolina, Hopp Children's Cancer Center Heidelberg, Deutsches Konsortium für Translationale Krebsforschung, Hospital Del Mar, Hospital del Mar Research Institute, The University of Texas MD Anderson Cancer Center, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria di Modena, Mayo Clinic, Hospital Universitario Virgen de las Nieves, Hospital General Universitario Morales Meseguer, MSB Medical School Berlin, Generalitat de Catalunya, Universitat de Girona, Josep Carreras Leukaemia Research Institute, Departament de Salut, Institut d'Investigació Biomèdica de Girona, Universidad de Salamanca, Instituto de Investigación Biomédica de Salamanca, Centro de Investigación Biomédica en Red de Cáncer, Instituto de Biología Molecular y Celular del Cáncer de Salamanca, Universidad de Cantabria, Vall d'Hebron Hospital Universitari, Vall d'Hebron Institute of Oncology, University of Wrocław, Wroclaw Medical University, Charles University, Radboud University Nijmegen, Radboud University Medical Center, Medizinische Hochschule Hannover, Helmholtz Centre for Infection Research, Centre for Individualised Infection Medicine, Center for Experimental and Clinical Infection Research, National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics, University of Bonn
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,780
Funders: Università Degli Studi di Modena e Reggio Emila, Consejería de Transformación Económica, Industria, Conocimiento y Universidades, European Commission, Radboud Universiteit, Radboud Universitair Medisch Centrum, Università di Pisa, Uniwersytet Medyczny im. Piastów Slaskich we Wroclawiu, National Institutes of Health, Instituto de Salud Carlos III, National Cancer Institute
Awards: ERA Chair Position for Excellent Research in Oncology, G2111860640, G2190235346, G2660289629, Aproximación multi-OMICA para la caracterización de la leucemia mieloide aguda de novo y secundaria: estudio en el contexto del consorcio NuCLEAR y el Grupo Español de Síndromes Mielodisplasicos, G3602838194, G4109967073, G4225195792, G434337789, G6255981358, G6622425196, Molecular Epidemiology of NHL and CLL, G7822233629, G792371430, G8395321922, Lymphoma Specialized Program of Research Excellence (SPORE) in Human Cancer, Mayo Clinic Comprehensive Cancer Center Support Grant
OpenAlex ID: W4367311543