Do GWAS-Identified Risk Variants for Chronic Lymphocytic Leukemia Influence Overall Patient Survival and Disease Progression?

Autor: Cabrera-Serrano AJ; Genomic Oncology Area, GENYO, Centre for Genomics and Oncological Research: Pfizer/University of Granada/Andalusian Regional Government, PTS, 18016 Granada, Spain.; Instituto de Investigación Biosanitaria IBs.Granada, 18012 Granada, Spain., Sánchez-Maldonado JM; Genomic Oncology Area, GENYO, Centre for Genomics and Oncological Research: Pfizer/University of Granada/Andalusian Regional Government, PTS, 18016 Granada, Spain.; Instituto de Investigación Biosanitaria IBs.Granada, 18012 Granada, Spain., Ter Horst R; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria., Macauda A; Genomic Epidemiology Group, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany., García-Martín P; Hospital Campus de la Salud, PTS, 18016 Granada, Spain., Benavente Y; Catalan Institute of Oncology, Bellvitge Biomedical Research Institute (IDIBELL), 08908 Barcelona, Spain.; Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), University of Barcelona, 08908 Barcelona, Spain.; CIBER Epidemiología y Salud Pública (CIBERESP), 28029 Madrid, Spain., Landi S; Department of Biology, University of Pisa, 56126 Pisa, Italy., Clay-Gilmour A; Department of Epidemiology & Biostatistics, Arnold School of Public Health, University of South Carolina, Greenville, SC 29208, USA., Niazi Y; Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), 69120 Heidelberg, Germany.; Hopp Children's Cancer Center (KiTZ), 69120 Heidelberg, Germany., Espinet B; Molecular Cytogenetics Laboratory, Pathology Department, Hospital del Mar, 08003 Barcelona, Spain.; Translational Research on Hematological Neoplasms Group, Cancer Research Program, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), 08003 Barcelona, Spain., Rodríguez-Sevilla JJ; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Pérez EM; Hospital Campus de la Salud, PTS, 18016 Granada, Spain., Maffei R; Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, AOU Policlinico, 41124 Modena, Italy., Blanco G; Molecular Cytogenetics Laboratory, Pathology Department, Hospital del Mar, 08003 Barcelona, Spain.; Translational Research on Hematological Neoplasms Group, Cancer Research Program, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), 08003 Barcelona, Spain., Giaccherini M; Department of Biology, University of Pisa, 56126 Pisa, Italy., Cerhan JR; Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN 55905, USA., Marasca R; Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, AOU Policlinico, 41124 Modena, Italy., López-Nevot MÁ; Immunology Department, Virgen de las Nieves University Hospital, 18014 Granada, Spain., Chen-Liang T; Hematology Department, Morales Meseguer University Hospital, 30008 Murcia, Spain., Thomsen H; MSB Medical School Berlin, D-14197 Berlin, Germany., Gámez I; Hematology Department, Morales Meseguer University Hospital, 30008 Murcia, Spain., Campa D; Department of Biology, University of Pisa, 56126 Pisa, Italy., Moreno V; Catalan Institute of Oncology, Bellvitge Biomedical Research Institute (IDIBELL), 08908 Barcelona, Spain.; Cancer Prevention and Control Program, Unit of Biomarkers and Susceptibility, Bellvitge Biomedical Research Institute (IDIBELL), Catalan Institute of Oncology, 08907 Barcelona, Spain.; Department of Clinical Sciences, Faculty of Medicine, University of Barcelona, 08907 Barcelona, Spain., de Sanjosé S; Catalan Institute of Oncology, Bellvitge Biomedical Research Institute (IDIBELL), 08908 Barcelona, Spain.; Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), University of Barcelona, 08908 Barcelona, Spain., Marcos-Gragera R; Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), University of Barcelona, 08908 Barcelona, Spain.; Epidemiology Unit and Girona Cancer Registry, Oncology Coordination Plan, Department of Health, Autonomous Government of Catalonia, Catalan Institute of Oncology, Girona Biomedical Research Institute (IdiBGi), 17190 Girona, Spain.; Department of Nursing, Universitat de Girona, 17007 Girona, Spain.; Josep Carreras Leukemia Research Institute, 08916 Girona, Spain., García-Álvarez M; Department of Hematology, University Hospital of Salamanca (HUS/IBSAL), CIBERONC and Cancer Research Institute of Salamanca-IBMCC (USAL-CSIC), 37007 Salamanca, Spain., Dierssen-Sotos T; Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), University of Barcelona, 08908 Barcelona, Spain.; Faculty of Medicine, University of Cantabria, 39011 Santander, Spain., Jerez A; Department of Hematology, Experimental Hematology Unit, Vall d'Hebron Institute of Oncology (VHIO), University Hospital Vall d'Hebron, 08035 Barcelona, Spain., Butrym A; Department of Cancer Prevention and Therapy, Medical University of Wrocław, 50-556 Wrocław, Poland., Norman AD; Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN 55905, USA., Luppi M; Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, AOU Policlinico, 41124 Modena, Italy., Slager SL; Division of Computational Genomics, Mayo Clinic, Rochester, MN 85054, USA.; Division of Hematology, Mayo Clinic, Rochester, MN 55905, USA., Hemminki K; Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.; Faculty of Medicine and Biomedical Center in Pilsen, Charles University in Prague, 30605 Pilsen, Czech Republic., Li Y; Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands.; Centre for Individualised Infection Medicine (CiiM) & TWINCORE, Joint Ventures between the Helmholtz-Centre for Infection Research (HZI) and the Hannover Medical School (MHH), 30625 Hannover, Germany., Berndt SI; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20814, USA., Casabonne D; Catalan Institute of Oncology, Bellvitge Biomedical Research Institute (IDIBELL), 08908 Barcelona, Spain.; Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), University of Barcelona, 08908 Barcelona, Spain., Alcoceba M; Department of Hematology, University Hospital of Salamanca (HUS/IBSAL), CIBERONC and Cancer Research Institute of Salamanca-IBMCC (USAL-CSIC), 37007 Salamanca, Spain., Puiggros A; Molecular Cytogenetics Laboratory, Pathology Department, Hospital del Mar, 08003 Barcelona, Spain.; Translational Research on Hematological Neoplasms Group, Cancer Research Program, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), 08003 Barcelona, Spain., Netea MG; Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands.; Department for Immunology & Metabolism, Life and Medical Sciences Institute (LIMES), University of Bonn, 53115 Bonn, Germany., Försti A; Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), 69120 Heidelberg, Germany.; Hopp Children's Cancer Center (KiTZ), 69120 Heidelberg, Germany., Canzian F; Genomic Epidemiology Group, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany., Sainz J; Genomic Oncology Area, GENYO, Centre for Genomics and Oncological Research: Pfizer/University of Granada/Andalusian Regional Government, PTS, 18016 Granada, Spain.; Instituto de Investigación Biosanitaria IBs.Granada, 18012 Granada, Spain.; Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), University of Barcelona, 08908 Barcelona, Spain.; Department of Biochemistry and Molecular Biology I, Faculty of Sciences, University of Granada (UGR), 18012 Granada, Spain.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2023 Apr 28; Vol. 24 (9). Date of Electronic Publication: 2023 Apr 28.
DOI: 10.3390/ijms24098005
Abstrakt: 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.
Databáze: MEDLINE
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