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

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.

Otras publicaciones de la misma revista o congreso con autores/as de la Universidad de Cantabria

 Autoría: Cabrera-Serrano A.J., Sánchez-Maldonado J.M., ter Horst R., Macauda A., García-Martín P., Benavente Y., Landi S., Clay-Gilmour A., Niazi Y., Espinet B., Rodríguez-Sevilla J.J., Pérez E.M., Maffei R., Blanco G., Giaccherini M., Cerhan J.R., Marasca R., López-Nevot M.Á., Chen-Liang T., Thomsen H., Gámez I., Campa D., Moreno V., de Sanjosé S., Marcos-Gragera R., García-Álvarez M., Dierssen-Sotos T., Jerez A., Butrym A., Norman A.D., Luppi

 Fuente: International Journal of Molecular Sciences, 2023, 24, 8005

Editorial: MDPI

 Año de publicación: 2023

Nº de páginas: 11

Tipo de publicación: Artículo de Revista

 DOI: 10.3390/ijms24098005

ISSN: 1661-6596,1422-0067

Autores/as

CABRERA-SERRANO, ANTONIO JOSÉ

SÁNCHEZ-MALDONADO, JOSÉ MANUEL

HORST, ROB TER

MACAUDA, ANGELICA

GARCÍA-MARTÍN, PALOMA

BENAVENTE, YOLANDA

LANDI, STEFANO

GLAY-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