Do GWAS-Identified Risk Variants for Chronic Lymphocytic Leukemia Influence Overall Patient Survival and Disease Progression?
Cabrera Serrano, Antonio José (Instituto de Investigación Sanitaria de Granada)
Sánchez Maldonado, José Manuel (Instituto de Investigación Sanitaria de Granada)
ter Horst, Rob (CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences)
Macauda, Angelica (German Cancer Research Center)
García Martín, Paloma (Hospital Campus de la Salud (Granada))
Benavente, Yolanda (Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública)
Landi, Stefano (Department of Biology. University of Pisa)
Clay-Gilmour, Alyssa (Department of Epidemiology & Biostatistics. Arnold School of Public Health. University of South Carolina)
Niazi, Yasmeen (Hopp Children's Cancer Center)
Espinet, Blanca (Institut Hospital del Mar d'Investigacions Mèdiques)
Rodriguez-Sevilla, Juan Jose (Department of Leukemia. The University of Texas MD Anderson Cancer Center)
Pérez, Eva María (Hospital Campus de la Salud)
Maffei, Rossana (University of Modena and Reggio Emilia)
Blanco, Gonzalo (Institut Hospital del Mar d'Investigacions Mèdiques)
Giaccherini, Matteo (Department of Biology. University of Pisa)
Cerhan, James R. (Department of Quantitative Health Sciences. Mayo Clinic)
Marasca, Roberto (Department of Medical and Surgical Sciences. University of Modena and Reggio Emilia. AOU Policlinico)
Lopez Nevot, Miguel Angel (Hospital Universitario Virgen de las Nieves (Granada))
Chen-Liang, Tzu Hua (Hospital Universitario Morales Meseguer (Múrcia))
Thomsen, Hauke (MSB Medical School Berlin)
Gámez, Irene (Hematology Department. Morales Meseguer University Hospital)
Campa, Daniele (Department of Biology. University of Pisa)
Moreno Aguado, Víctor (Facultat de Medicina. Universitat de Barcelona)
de Sanjosé, Silvia (Universitat de Barcelona)
Marcos-Gragera, Rafael (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
García-Álvarez, María Flor (Instituto de Investigación Biomédica de Salamanca)
Dierssen-Sotos, Trinidad (Universidad de Cantabria)
Jerez, Andrés (Vall d'Hebron Institut d'Oncologia)
Butrym, Aleksandra (Department of Cancer Prevention and Therapy. Medical University of Wrocław)
Norman, Aaron D. (Department of Quantitative Health Sciences. Mayo Clinic)
Luppi, Mario (University of Modena and Reggio Emilia)
Slager, Susan L. (Mayo Clinic)
Hemminki, Kari (Charles University in Prague)
Li, Yang (Hannover Medical School)
Berndt, Sonja I. (National Institutes of Health (Estats Units d'Amèrica))
Casabonne, Delphine (Universitat de Barcelona)
Alcoceba, Miguel (Instituto de Investigación Biomédica de Salamanca)
Puiggros, Anna (Institut Hospital del Mar d'Investigacions Mèdiques)
Netea, Mihai G. (Department for Immunology & Metabolism. University of Bonn)
Försti, Asta (Hopp Children's Cancer Center)
Canzian, Federico (German Cancer Research Center)
Sainz, Juan (Department of Biochemistry and Molecular Biology. Universidad de Granada)

Data:	2023
Resum:	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.
Ajuts:	European Commission. Horizon 2020 856620 Instituto de Salud Carlos III PI17/02256 Instituto de Salud Carlos III PI20/01845
Nota:	This work was supported by the European Union's Horizon 2020 research and innovation program, N° 856620 and by grants from the Instituto de Salud Carlos III and FEDER (Madrid, Spain; PI17/02256 and PI20/01845) and from the Consejería de Transformación Económica, Industria, Conocimiento y Universidades y FEDER (PY20/01282). "The Mayo studies in InterLymph were supported in part by the US National Cancer Institute grants P50 CA97274 and R01 CA92153."
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Chronic lymphocytic leukemia ; Overall survival ; TTFT ; Genetic variants ; Susceptibility ; Polygenic risk score
Publicat a:	International journal of molecular sciences, Vol. 24 Núm. 9 (may 2023) , p. 8005, ISSN 1422-0067

DOI: 10.3390/ijms24098005
PMID: 37175717

11 p, 771.0 KB

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