{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T08:22:49Z","timestamp":1765354969089,"version":"build-2065373602"},"reference-count":18,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,4,28]],"date-time":"2023-04-28T00:00:00Z","timestamp":1682640000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union\u2019s Horizon 2020 research and innovation program","award":["856620","PI17\/02256","PI20\/01845","PY20\/01282","P50 CA97274","R01 CA92153"],"award-info":[{"award-number":["856620","PI17\/02256","PI20\/01845","PY20\/01282","P50 CA97274","R01 CA92153"]}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III and FEDER","doi-asserted-by":"publisher","award":["856620","PI17\/02256","PI20\/01845","PY20\/01282","P50 CA97274","R01 CA92153"],"award-info":[{"award-number":["856620","PI17\/02256","PI20\/01845","PY20\/01282","P50 CA97274","R01 CA92153"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Consejer\u00eda de Transformaci\u00f3n Econ\u00f3mica, Industria, Conocimiento y Universidades y FEDER","award":["856620","PI17\/02256","PI20\/01845","PY20\/01282","P50 CA97274","R01 CA92153"],"award-info":[{"award-number":["856620","PI17\/02256","PI20\/01845","PY20\/01282","P50 CA97274","R01 CA92153"]}]},{"name":"US National Cancer Institute","award":["856620","PI17\/02256","PI20\/01845","PY20\/01282","P50 CA97274","R01 CA92153"],"award-info":[{"award-number":["856620","PI17\/02256","PI20\/01845","PY20\/01282","P50 CA97274","R01 CA92153"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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 &lt; 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 &lt; 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.<\/jats:p>","DOI":"10.3390\/ijms24098005","type":"journal-article","created":{"date-parts":[[2023,4,28]],"date-time":"2023-04-28T10:51:52Z","timestamp":1682679112000},"page":"8005","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Do GWAS-Identified Risk Variants for Chronic Lymphocytic Leukemia Influence Overall Patient Survival and Disease Progression?"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0346-7960","authenticated-orcid":false,"given":"Antonio Jos\u00e9","family":"Cabrera-Serrano","sequence":"first","affiliation":[{"name":"Genomic Oncology Area, GENYO, Centre for Genomics and Oncological Research: Pfizer\/University of Granada\/Andalusian Regional Government, PTS, 18016 Granada, Spain"},{"name":"Instituto de Investigaci\u00f3n Biosanitaria IBs.Granada, 18012 Granada, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4651-3675","authenticated-orcid":false,"given":"Jos\u00e9 Manuel","family":"S\u00e1nchez-Maldonado","sequence":"additional","affiliation":[{"name":"Genomic Oncology Area, GENYO, Centre for Genomics and Oncological Research: Pfizer\/University of Granada\/Andalusian Regional Government, PTS, 18016 Granada, Spain"},{"name":"Instituto de Investigaci\u00f3n Biosanitaria IBs.Granada, 18012 Granada, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rob","family":"ter Horst","sequence":"additional","affiliation":[{"name":"CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angelica","family":"Macauda","sequence":"additional","affiliation":[{"name":"Genomic Epidemiology Group, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paloma","family":"Garc\u00eda-Mart\u00edn","sequence":"additional","affiliation":[{"name":"Hospital Campus de la Salud, PTS, 18016 Granada, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1422-4614","authenticated-orcid":false,"given":"Yolanda","family":"Benavente","sequence":"additional","affiliation":[{"name":"Catalan Institute of Oncology, Bellvitge Biomedical Research Institute (IDIBELL), 08908 Barcelona, Spain"},{"name":"Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), University of Barcelona, 08908 Barcelona, Spain"},{"name":"CIBER Epidemiolog\u00eda y Salud P\u00fablica (CIBERESP), 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8364-6357","authenticated-orcid":false,"given":"Stefano","family":"Landi","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Pisa, 56126 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alyssa","family":"Clay-Gilmour","sequence":"additional","affiliation":[{"name":"Department of Epidemiology & Biostatistics, Arnold School of Public Health, University of South Carolina, Greenville, SC 29208, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasmeen","family":"Niazi","sequence":"additional","affiliation":[{"name":"Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), 69120 Heidelberg, Germany"},{"name":"Hopp Children\u2019s Cancer Center (KiTZ), 69120 Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4294-8145","authenticated-orcid":false,"given":"Blanca","family":"Espinet","sequence":"additional","affiliation":[{"name":"Molecular Cytogenetics Laboratory, Pathology Department, Hospital del Mar, 08003 Barcelona, Spain"},{"name":"Translational Research on Hematological Neoplasms Group, Cancer Research Program, Institut Hospital del Mar d\u2019Investigacions M\u00e8diques (IMIM), 08003 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4741-7925","authenticated-orcid":false,"given":"Juan Jos\u00e9","family":"Rodr\u00edguez-Sevilla","sequence":"additional","affiliation":[{"name":"Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eva 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Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9627-4978","authenticated-orcid":false,"given":"Anna","family":"Puiggros","sequence":"additional","affiliation":[{"name":"Molecular Cytogenetics Laboratory, Pathology Department, Hospital del Mar, 08003 Barcelona, Spain"},{"name":"Translational Research on Hematological Neoplasms Group, Cancer Research Program, Institut Hospital del Mar d\u2019Investigacions M\u00e8diques (IMIM), 08003 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mihai G.","family":"Netea","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands"},{"name":"Department for Immunology & Metabolism, Life and Medical Sciences Institute (LIMES), University of Bonn, 53115 Bonn, 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