학술논문
Do GWAS-Identified Risk Variants for Chronic Lymphocytic Leukemia Influence Overall Patient Survival and Disease Progression?
Document Type
article
Author
Antonio José Cabrera-Serrano; José Manuel Sánchez-Maldonado; Rob ter Horst; Angelica Macauda; Paloma García-Martín; Yolanda Benavente; Stefano Landi; Alyssa Clay-Gilmour; Yasmeen Niazi; Blanca Espinet; Juan José Rodríguez-Sevilla; Eva María Pérez; Rossana Maffei; Gonzalo Blanco; Matteo Giaccherini; James R. Cerhan; Roberto Marasca; Miguel Ángel López-Nevot; Tzu Chen-Liang; Hauke Thomsen; Irene Gámez; Daniele Campa; Víctor Moreno; Silvia de Sanjosé; Rafael Marcos-Gragera; María García-Álvarez; Trinidad Dierssen-Sotos; Andrés Jerez; Aleksandra Butrym; Aaron D. Norman; Mario Luppi; Susan L. Slager; Kari Hemminki; Yang Li; Sonja I. Berndt; Delphine Casabonne; Miguel Alcoceba; Anna Puiggros; Mihai G. Netea; Asta Försti; Federico Canzian; Juan Sainz
Source
International Journal of Molecular Sciences, Vol 24, Iss 9, p 8005 (2023)
Subject
Language
English
ISSN
1422-0067
1661-6596
1661-6596
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.