Journal Article

DKFZ-2023-00972

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Do GWAS-Identified Risk Variants for Chronic Lymphocytic Leukemia Influence Overall Patient Survival and Disease Progression?

Cabrera-Serrano, A. J. ; Sánchez-Maldonado, J. M. ; Ter Horst, R. ; Macauda, A.DKFZ* ; García-Martín, P. ; Benavente, Y. ; Landi, S. ; Clay-Gilmour, A. ; Niazi, Y.DKFZ* ; Espinet, B. ; Rodríguez-Sevilla, J. J. ; Pérez, E. M. ; Maffei, R. ; Blanco, G. ; Giaccherini, M. ; Cerhan, J. R. ; Marasca, R. ; López-Nevot, M. Á. ; Chen-Liang, T. ; Thomsen, H. ; Gámez, I. ; Campa, D. ; Moreno, V. ; de Sanjosé, S. ; Marcos-Gragera, R. ; García-Álvarez, M. ; Dierssen-Sotos, T. ; Jerez, A. ; Butrym, A. ; Norman, A. D. ; Luppi, M. ; Slager, S. L. ; Hemminki, K.DKFZ* ; Li, Y. ; Berndt, S. I. ; Casabonne, D. ; Alcoceba, M. ; Puiggros, A. ; Netea, M. G. ; Försti, A.DKFZ* ; Canzian, F.DKFZ* ; Sainz, J.

2023
Molecular Diversity Preservation International Basel

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Please use a persistent id in citations: doi:10.3390/ijms24098005

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.

Keyword(s): Adult (MeSH) ; Humans (MeSH) ; Leukemia, Lymphocytic, Chronic, B-Cell: genetics (MeSH) ; Genome-Wide Association Study (MeSH) ; Risk Factors (MeSH) ; Disease Progression (MeSH) ; Genetic Predisposition to Disease (MeSH) ; Polymorphism, Single Nucleotide (MeSH) ; TTFT ; chronic lymphocytic leukemia ; genetic variants ; overall survival ; polygenic risk score ; susceptibility

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Contributing Institute(s):

1. Genomische Epidemiologie (C055)
2. B062 Pädiatrische Neuroonkologie (B062)
3. DKTK HD zentral (HD01)
4. C020 Epidemiologie von Krebs (C020)

Research Program(s):

1. 313 - Krebsrisikofaktoren und Prävention (POF4-313) (POF4-313)

Appears in the scientific report 2023

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Database coverage:
; ; ; Article Processing Charges ; Clarivate Analytics Master Journal List ; Current Contents - Physical, Chemical and Earth Sciences ; DOAJ Seal ; Ebsco Academic Search ; Essential Science Indicators ; Fees ; IF >= 5 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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