Journal article
Do GWAS-Identified Risk Variants for Chronic Lymphocytic Leukemia Influence Overall Patient Survival and Disease Progression?
International journal of molecular sciences, Vol.24(9), p.8005
04/28/2023
DOI: 10.3390/ijms24098005
PMCID: PMC10178669
PMID: 37175717
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 (
< 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 (
< 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.
Details
- Title: Subtitle
- Do GWAS-Identified Risk Variants for Chronic Lymphocytic Leukemia Influence Overall Patient Survival and Disease Progression?
- Creators
- Antonio José Cabrera-Serrano - Pfizer-University of Granada-Junta de Andalucía Centre for Genomics and Oncological ResearchJosé Manuel Sánchez-Maldonado - Pfizer-University of Granada-Junta de Andalucía Centre for Genomics and Oncological ResearchRob Ter Horst - CeMM Research Center for Molecular MedicineAngelica Macauda - German Cancer Research CenterPaloma García-Martín - Parque Tecnológico de la SaludYolanda Benavente - Institut d'Investigació Biomédica de BellvitgeStefano Landi - University of PisaAlyssa Clay-Gilmour - University of South CarolinaYasmeen Niazi - German Cancer Research CenterBlanca Espinet - Hospital Del MarJuan José Rodríguez-Sevilla - The University of Texas MD Anderson Cancer CenterEva María Pérez - Parque Tecnológico de la SaludRossana Maffei - University of Modena and Reggio EmiliaGonzalo Blanco - Hospital Del MarMatteo Giaccherini - University of PisaJames R Cerhan - Mayo ClinicRoberto Marasca - University of Modena and Reggio EmiliaMiguel Ángel López-Nevot - Hospital Universitario Virgen de las NievesTzu Chen-Liang - Hospital General Universitario Morales MeseguerHauke Thomsen - MSB Medical School BerlinIrene Gámez - Hematology Department, Morales Meseguer University Hospital, 30008 Murcia, SpainDaniele Campa - University of PisaVíctor Moreno - Institut d'Investigació Biomédica de BellvitgeSilvia de Sanjosé - Institut d'Investigació Biomédica de BellvitgeRafael Marcos-Gragera - Centro de Investigación Biomédica en Red de Epidemiología y Salud PúblicaMaría García-Álvarez - Centro de Investigación del CáncerTrinidad Dierssen-Sotos - Centro de Investigación Biomédica en Red de Epidemiología y Salud PúblicaAndrés Jerez - Vall d'Hebron Hospital UniversitariAleksandra Butrym - University of WrocławAaron D Norman - Mayo ClinicMario Luppi - University of Modena and Reggio EmiliaSusan L Slager - Mayo Clinic in FloridaKari Hemminki - German Cancer Research CenterYang Li - Centre for Individualised Infection MedicineSonja I Berndt - National Institutes of HealthDelphine Casabonne - Institut d'Investigació Biomédica de BellvitgeMiguel Alcoceba - Centro de Investigación del CáncerAnna Puiggros - Hospital Del MarMihai G Netea - Radboud University NijmegenAsta Försti - German Cancer Research CenterFederico Canzian - German Cancer Research CenterJuan Sainz - Pfizer-University of Granada-Junta de Andalucía Centre for Genomics and Oncological Research
- Resource Type
- Journal article
- Publication Details
- International journal of molecular sciences, Vol.24(9), p.8005
- DOI
- 10.3390/ijms24098005
- PMID
- 37175717
- PMCID
- PMC10178669
- NLM abbreviation
- Int J Mol Sci
- ISSN
- 1422-0067
- eISSN
- 1422-0067
- Grant note
- PY20/01282 / The Consejería de Salud y Familia de la Junta de Andalucía PI20/01845 / Instituto de Salud Carlos III PI17/02256 / Instituto de Salud Carlos III
- Language
- English
- Date published
- 04/28/2023
- Academic Unit
- Epidemiology
- Record Identifier
- 9984413072502771
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