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000276066 1001_ $$00000-0003-0346-7960$$aCabrera-Serrano, Antonio José$$b0
000276066 245__ $$aDo GWAS-Identified Risk Variants for Chronic Lymphocytic Leukemia Influence Overall Patient Survival and Disease Progression?
000276066 260__ $$aBasel$$bMolecular Diversity Preservation International$$c2023
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000276066 520__ $$aChronic 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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000276066 650_7 $$2Other$$aTTFT
000276066 650_7 $$2Other$$achronic lymphocytic leukemia
000276066 650_7 $$2Other$$agenetic variants
000276066 650_7 $$2Other$$aoverall survival
000276066 650_7 $$2Other$$apolygenic risk score
000276066 650_7 $$2Other$$asusceptibility
000276066 650_2 $$2MeSH$$aAdult
000276066 650_2 $$2MeSH$$aHumans
000276066 650_2 $$2MeSH$$aLeukemia, Lymphocytic, Chronic, B-Cell: genetics
000276066 650_2 $$2MeSH$$aGenome-Wide Association Study
000276066 650_2 $$2MeSH$$aRisk Factors
000276066 650_2 $$2MeSH$$aDisease Progression
000276066 650_2 $$2MeSH$$aGenetic Predisposition to Disease
000276066 650_2 $$2MeSH$$aPolymorphism, Single Nucleotide
000276066 7001_ $$00000-0002-4651-3675$$aSánchez-Maldonado, José Manuel$$b1
000276066 7001_ $$aTer Horst, Rob$$b2
000276066 7001_ $$0P:(DE-He78)b791a47b92809f7c54501331f72e0243$$aMacauda, Angelica$$b3$$udkfz
000276066 7001_ $$aGarcía-Martín, Paloma$$b4
000276066 7001_ $$00000-0003-1422-4614$$aBenavente, Yolanda$$b5
000276066 7001_ $$00000-0001-8364-6357$$aLandi, Stefano$$b6
000276066 7001_ $$aClay-Gilmour, Alyssa$$b7
000276066 7001_ $$0P:(DE-He78)0681b959321f574e7ad1869cc3011346$$aNiazi, Yasmeen$$b8$$udkfz
000276066 7001_ $$00000-0002-4294-8145$$aEspinet, Blanca$$b9
000276066 7001_ $$00000-0002-4741-7925$$aRodríguez-Sevilla, Juan José$$b10
000276066 7001_ $$aPérez, Eva María$$b11
000276066 7001_ $$00000-0002-3518-2006$$aMaffei, Rossana$$b12
000276066 7001_ $$00000-0001-6557-3764$$aBlanco, Gonzalo$$b13
000276066 7001_ $$aGiaccherini, Matteo$$b14
000276066 7001_ $$aCerhan, James R$$b15
000276066 7001_ $$00000-0002-6431-6878$$aMarasca, Roberto$$b16
000276066 7001_ $$00000-0002-3465-6062$$aLópez-Nevot, Miguel Ángel$$b17
000276066 7001_ $$aChen-Liang, Tzu$$b18
000276066 7001_ $$aThomsen, Hauke$$b19
000276066 7001_ $$aGámez, Irene$$b20
000276066 7001_ $$aCampa, Daniele$$b21
000276066 7001_ $$00000-0002-2818-5487$$aMoreno, Víctor$$b22
000276066 7001_ $$ade Sanjosé, Silvia$$b23
000276066 7001_ $$00000-0001-9824-3657$$aMarcos-Gragera, Rafael$$b24
000276066 7001_ $$aGarcía-Álvarez, María$$b25
000276066 7001_ $$00000-0002-6127-0077$$aDierssen-Sotos, Trinidad$$b26
000276066 7001_ $$00000-0002-2079-6638$$aJerez, Andrés$$b27
000276066 7001_ $$00000-0002-8199-2018$$aButrym, Aleksandra$$b28
000276066 7001_ $$aNorman, Aaron D$$b29
000276066 7001_ $$aLuppi, Mario$$b30
000276066 7001_ $$aSlager, Susan L$$b31
000276066 7001_ $$0P:(DE-He78)19b0ec1cea271419d9fa8680e6ed6865$$aHemminki, Kari$$b32$$udkfz
000276066 7001_ $$00000-0003-4022-7341$$aLi, Yang$$b33
000276066 7001_ $$aBerndt, Sonja I$$b34
000276066 7001_ $$aCasabonne, Delphine$$b35
000276066 7001_ $$00000-0002-3819-4846$$aAlcoceba, Miguel$$b36
000276066 7001_ $$00000-0001-9627-4978$$aPuiggros, Anna$$b37
000276066 7001_ $$aNetea, Mihai G$$b38
000276066 7001_ $$0P:(DE-He78)f26164c08f2f14abcf31e52e13ee3696$$aFörsti, Asta$$b39$$udkfz
000276066 7001_ $$0P:(DE-He78)5323704270b6393dcea70186ffd86bca$$aCanzian, Federico$$b40$$udkfz
000276066 7001_ $$00000-0002-9355-2423$$aSainz, Juan$$b41
000276066 773__ $$0PERI:(DE-600)2019364-6$$a10.3390/ijms24098005$$gVol. 24, no. 9, p. 8005 -$$n9$$p8005$$tInternational journal of molecular sciences$$v24$$x1422-0067$$y2023
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