Do gwas-identified risk variants for chronic lymphocytic leukemia influence overall patient survival and disease progression?

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  • dc.contributor.author Cabrera Serrano, Antonio José
  • dc.contributor.author Espinet Solà, Blanca
  • dc.contributor.author Blanco Ares, Gonzalo, 1989-
  • dc.contributor.author Puiggros Metje, Anna Maria
  • dc.contributor.author Sainz, Juan
  • dc.date.accessioned 2024-03-07T07:11:57Z
  • dc.date.available 2024-03-07T07:11:57Z
  • dc.date.issued 2023
  • dc.description.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.
  • dc.description.sponsorship 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.”
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Cabrera-Serrano AJ, Sánchez-Maldonado JM, Ter Horst R, Macauda A, García-Martín P, Benavente Y et al. Do gwas-identified risk variants for chronic lymphocytic leukemia influence overall patient survival and disease progression?. Int J Mol Sci. 2023 Apr 28;24(9):8005. DOI: 10.3390/ijms24098005
  • dc.identifier.doi http://dx.doi.org/10.3390/ijms24098005
  • dc.identifier.issn 1422-0067
  • dc.identifier.uri http://hdl.handle.net/10230/59343
  • dc.language.iso eng
  • dc.publisher MDPI
  • dc.relation.ispartof Int J Mol Sci. 2023 Apr 28;24(9):8005
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/856620
  • dc.rights © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by/4.0/
  • dc.subject.keyword TTFT
  • dc.subject.keyword Chronic lymphocytic leukemia
  • dc.subject.keyword Genetic variants
  • dc.subject.keyword Overall survival
  • dc.subject.keyword Polygenic risk score
  • dc.subject.keyword Susceptibility
  • dc.title Do gwas-identified risk variants for chronic lymphocytic leukemia influence overall patient survival and disease progression?
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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