TY - JOUR
T1 - Do GWAS-Identified Risk Variants for Chronic Lymphocytic Leukemia Influence Overall Patient Survival and Disease Progression?
AU - Cabrera-Serrano, Antonio José
AU - Sánchez-Maldonado, José Manuel
AU - ter Horst, Rob
AU - Macauda, Angelica
AU - García-Martín, Paloma
AU - Benavente, Yolanda
AU - Landi, Stefano
AU - Clay-Gilmour, Alyssa
AU - Niazi, Yasmeen
AU - Espinet, Blanca
AU - Rodríguez-Sevilla, Juan José
AU - Pérez, Eva María
AU - Maffei, Rossana
AU - Blanco, Gonzalo
AU - Giaccherini, Matteo
AU - Cerhan, James R.
AU - Marasca, Roberto
AU - López-Nevot, Miguel Ángel
AU - Chen-Liang, Tzu
AU - Thomsen, Hauke
AU - Gámez, Irene
AU - Campa, Daniele
AU - Moreno, Víctor
AU - de Sanjosé, Silvia
AU - Marcos-Gragera, Rafael
AU - García-Álvarez, María
AU - Dierssen-Sotos, Trinidad
AU - Jerez, Andrés
AU - Butrym, Aleksandra
AU - Norman, Aaron D.
AU - Luppi, Mario
AU - Slager, Susan L.
AU - Hemminki, Kari
AU - Li, Yang
AU - Berndt, Sonja I.
AU - Casabonne, Delphine
AU - Alcoceba, Miguel
AU - Puiggros, Anna
AU - Netea, Mihai G.
AU - Försti, Asta
AU - Canzian, Federico
AU - Sainz, Juan
N1 - Funding Information:
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.”
Publisher Copyright:
© 2023 by the authors.
PY - 2023/5
Y1 - 2023/5
N2 - 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.
AB - 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.
KW - chronic lymphocytic leukemia
KW - genetic variants
KW - overall survival
KW - polygenic risk score
KW - susceptibility
KW - TTFT
U2 - 10.3390/ijms24098005
DO - 10.3390/ijms24098005
M3 - Article
C2 - 37175717
AN - SCOPUS:85159295515
SN - 1661-6596
VL - 24
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 9
M1 - 8005
ER -