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- Title
Do GWAS-Identified Risk Variants for Chronic Lymphocytic Leukemia Influence Overall Patient Survival and Disease Progression?
- Authors
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
- 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.
- Subjects
CHRONIC lymphocytic leukemia; OVERALL survival; DISEASE progression; DISEASE risk factors; RECEIVER operating characteristic curves
- Publication
International Journal of Molecular Sciences, 2023, Vol 24, Issue 9, p8005
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms24098005