1. Do GWAS-Identified Risk Variants for Chronic Lymphocytic Leukemia Influence Overall Patient Survival and Disease Progression?
- Author
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Cabrera-Serrano, A.J., Sánchez-Maldonado, J.M., 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., Sanjosé, S. de, Marcos-Gragera, R., García-Álvarez, M., Dierssen-Sotos, T., Jerez, A., Butrym, A., Norman, A.D., Luppi, M., Slager, S.L., Hemminki, K., Li, Y., Berndt, S.I., Casabonne, D., Alcoceba, M., Puiggros, A., Netea, M.G., Försti, A., Canzian, F., Sainz, J., Cabrera-Serrano, A.J., Sánchez-Maldonado, J.M., 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., Sanjosé, S. de, Marcos-Gragera, R., García-Álvarez, M., Dierssen-Sotos, T., Jerez, A., Butrym, A., Norman, A.D., Luppi, M., Slager, S.L., Hemminki, K., Li, Y., Berndt, S.I., Casabonne, D., Alcoceba, M., Puiggros, A., Netea, M.G., Försti, A., Canzian, F., and Sainz, J.
- Abstract
Contains fulltext : 292738.pdf (Publisher’s version ) (Open Access), 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.
- Published
- 2023