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| 001 | 276066 | ||
| 005 | 20240918103400.0 | ||
| 024 | 7 | _ | |a 10.3390/ijms24098005 |2 doi |
| 024 | 7 | _ | |a pmid:37175717 |2 pmid |
| 024 | 7 | _ | |a pmc:PMC10178669 |2 pmc |
| 024 | 7 | _ | |a 1422-0067 |2 ISSN |
| 024 | 7 | _ | |a 1661-6596 |2 ISSN |
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| 037 | _ | _ | |a DKFZ-2023-00972 |
| 041 | _ | _ | |a English |
| 082 | _ | _ | |a 540 |
| 100 | 1 | _ | |a Cabrera-Serrano, Antonio José |0 0000-0003-0346-7960 |b 0 |
| 245 | _ | _ | |a Do GWAS-Identified Risk Variants for Chronic Lymphocytic Leukemia Influence Overall Patient Survival and Disease Progression? |
| 260 | _ | _ | |a Basel |c 2023 |b Molecular Diversity Preservation International |
| 336 | 7 | _ | |a article |2 DRIVER |
| 336 | 7 | _ | |a Output Types/Journal article |2 DataCite |
| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1726648418_11602 |2 PUB:(DE-HGF) |
| 336 | 7 | _ | |a ARTICLE |2 BibTeX |
| 336 | 7 | _ | |a JOURNAL_ARTICLE |2 ORCID |
| 336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
| 520 | _ | _ | |a 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. |
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| 588 | _ | _ | |a Dataset connected to CrossRef, PubMed, , Journals: inrepo02.dkfz.de |
| 650 | _ | 7 | |a TTFT |2 Other |
| 650 | _ | 7 | |a chronic lymphocytic leukemia |2 Other |
| 650 | _ | 7 | |a genetic variants |2 Other |
| 650 | _ | 7 | |a overall survival |2 Other |
| 650 | _ | 7 | |a polygenic risk score |2 Other |
| 650 | _ | 7 | |a susceptibility |2 Other |
| 650 | _ | 2 | |a Adult |2 MeSH |
| 650 | _ | 2 | |a Humans |2 MeSH |
| 650 | _ | 2 | |a Leukemia, Lymphocytic, Chronic, B-Cell: genetics |2 MeSH |
| 650 | _ | 2 | |a Genome-Wide Association Study |2 MeSH |
| 650 | _ | 2 | |a Risk Factors |2 MeSH |
| 650 | _ | 2 | |a Disease Progression |2 MeSH |
| 650 | _ | 2 | |a Genetic Predisposition to Disease |2 MeSH |
| 650 | _ | 2 | |a Polymorphism, Single Nucleotide |2 MeSH |
| 700 | 1 | _ | |a Sánchez-Maldonado, José Manuel |0 0000-0002-4651-3675 |b 1 |
| 700 | 1 | _ | |a Ter Horst, Rob |b 2 |
| 700 | 1 | _ | |a Macauda, Angelica |0 P:(DE-He78)b791a47b92809f7c54501331f72e0243 |b 3 |u dkfz |
| 700 | 1 | _ | |a García-Martín, Paloma |b 4 |
| 700 | 1 | _ | |a Benavente, Yolanda |0 0000-0003-1422-4614 |b 5 |
| 700 | 1 | _ | |a Landi, Stefano |0 0000-0001-8364-6357 |b 6 |
| 700 | 1 | _ | |a Clay-Gilmour, Alyssa |b 7 |
| 700 | 1 | _ | |a Niazi, Yasmeen |0 P:(DE-He78)0681b959321f574e7ad1869cc3011346 |b 8 |u dkfz |
| 700 | 1 | _ | |a Espinet, Blanca |0 0000-0002-4294-8145 |b 9 |
| 700 | 1 | _ | |a Rodríguez-Sevilla, Juan José |0 0000-0002-4741-7925 |b 10 |
| 700 | 1 | _ | |a Pérez, Eva María |b 11 |
| 700 | 1 | _ | |a Maffei, Rossana |0 0000-0002-3518-2006 |b 12 |
| 700 | 1 | _ | |a Blanco, Gonzalo |0 0000-0001-6557-3764 |b 13 |
| 700 | 1 | _ | |a Giaccherini, Matteo |b 14 |
| 700 | 1 | _ | |a Cerhan, James R |b 15 |
| 700 | 1 | _ | |a Marasca, Roberto |0 0000-0002-6431-6878 |b 16 |
| 700 | 1 | _ | |a López-Nevot, Miguel Ángel |0 0000-0002-3465-6062 |b 17 |
| 700 | 1 | _ | |a Chen-Liang, Tzu |b 18 |
| 700 | 1 | _ | |a Thomsen, Hauke |b 19 |
| 700 | 1 | _ | |a Gámez, Irene |b 20 |
| 700 | 1 | _ | |a Campa, Daniele |b 21 |
| 700 | 1 | _ | |a Moreno, Víctor |0 0000-0002-2818-5487 |b 22 |
| 700 | 1 | _ | |a de Sanjosé, Silvia |b 23 |
| 700 | 1 | _ | |a Marcos-Gragera, Rafael |0 0000-0001-9824-3657 |b 24 |
| 700 | 1 | _ | |a García-Álvarez, María |b 25 |
| 700 | 1 | _ | |a Dierssen-Sotos, Trinidad |0 0000-0002-6127-0077 |b 26 |
| 700 | 1 | _ | |a Jerez, Andrés |0 0000-0002-2079-6638 |b 27 |
| 700 | 1 | _ | |a Butrym, Aleksandra |0 0000-0002-8199-2018 |b 28 |
| 700 | 1 | _ | |a Norman, Aaron D |b 29 |
| 700 | 1 | _ | |a Luppi, Mario |b 30 |
| 700 | 1 | _ | |a Slager, Susan L |b 31 |
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| 700 | 1 | _ | |a Li, Yang |0 0000-0003-4022-7341 |b 33 |
| 700 | 1 | _ | |a Berndt, Sonja I |b 34 |
| 700 | 1 | _ | |a Casabonne, Delphine |b 35 |
| 700 | 1 | _ | |a Alcoceba, Miguel |0 0000-0002-3819-4846 |b 36 |
| 700 | 1 | _ | |a Puiggros, Anna |0 0000-0001-9627-4978 |b 37 |
| 700 | 1 | _ | |a Netea, Mihai G |b 38 |
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| 700 | 1 | _ | |a Sainz, Juan |0 0000-0002-9355-2423 |b 41 |
| 773 | _ | _ | |a 10.3390/ijms24098005 |g Vol. 24, no. 9, p. 8005 - |0 PERI:(DE-600)2019364-6 |n 9 |p 8005 |t International journal of molecular sciences |v 24 |y 2023 |x 1422-0067 |
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