International Journal of Molecular Sciences (Apr 2023)
Do GWAS-Identified Risk Variants for Chronic Lymphocytic Leukemia Influence Overall Patient Survival and Disease Progression?
- Antonio José Cabrera-Serrano,
- José Manuel Sánchez-Maldonado,
- Rob ter Horst,
- Angelica Macauda,
- Paloma García-Martín,
- Yolanda Benavente,
- Stefano Landi,
- Alyssa Clay-Gilmour,
- Yasmeen Niazi,
- Blanca Espinet,
- Juan José Rodríguez-Sevilla,
- Eva María Pérez,
- Rossana Maffei,
- Gonzalo Blanco,
- Matteo Giaccherini,
- James R. Cerhan,
- Roberto Marasca,
- Miguel Ángel López-Nevot,
- Tzu Chen-Liang,
- Hauke Thomsen,
- Irene Gámez,
- Daniele Campa,
- Víctor Moreno,
- Silvia de Sanjosé,
- Rafael Marcos-Gragera,
- María García-Álvarez,
- Trinidad Dierssen-Sotos,
- Andrés Jerez,
- Aleksandra Butrym,
- Aaron D. Norman,
- Mario Luppi,
- Susan L. Slager,
- Kari Hemminki,
- Yang Li,
- Sonja I. Berndt,
- Delphine Casabonne,
- Miguel Alcoceba,
- Anna Puiggros,
- Mihai G. Netea,
- Asta Försti,
- Federico Canzian,
- Juan Sainz
Affiliations
- Antonio José Cabrera-Serrano
- Genomic Oncology Area, GENYO, Centre for Genomics and Oncological Research: Pfizer/University of Granada/Andalusian Regional Government, PTS, 18016 Granada, Spain
- José Manuel Sánchez-Maldonado
- Genomic Oncology Area, GENYO, Centre for Genomics and Oncological Research: Pfizer/University of Granada/Andalusian Regional Government, PTS, 18016 Granada, Spain
- Rob ter Horst
- CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria
- Angelica Macauda
- Genomic Epidemiology Group, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
- Paloma García-Martín
- Hospital Campus de la Salud, PTS, 18016 Granada, Spain
- Yolanda Benavente
- Catalan Institute of Oncology, Bellvitge Biomedical Research Institute (IDIBELL), 08908 Barcelona, Spain
- Stefano Landi
- Department of Biology, University of Pisa, 56126 Pisa, Italy
- Alyssa Clay-Gilmour
- Department of Epidemiology & Biostatistics, Arnold School of Public Health, University of South Carolina, Greenville, SC 29208, USA
- Yasmeen Niazi
- Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), 69120 Heidelberg, Germany
- Blanca Espinet
- Molecular Cytogenetics Laboratory, Pathology Department, Hospital del Mar, 08003 Barcelona, Spain
- Juan José Rodríguez-Sevilla
- Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
- Eva María Pérez
- Hospital Campus de la Salud, PTS, 18016 Granada, Spain
- Rossana Maffei
- Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, AOU Policlinico, 41124 Modena, Italy
- Gonzalo Blanco
- Molecular Cytogenetics Laboratory, Pathology Department, Hospital del Mar, 08003 Barcelona, Spain
- Matteo Giaccherini
- Department of Biology, University of Pisa, 56126 Pisa, Italy
- James R. Cerhan
- Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN 55905, USA
- Roberto Marasca
- Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, AOU Policlinico, 41124 Modena, Italy
- Miguel Ángel López-Nevot
- Immunology Department, Virgen de las Nieves University Hospital, 18014 Granada, Spain
- Tzu Chen-Liang
- Hematology Department, Morales Meseguer University Hospital, 30008 Murcia, Spain
- Hauke Thomsen
- MSB Medical School Berlin, D-14197 Berlin, Germany
- Irene Gámez
- Hematology Department, Morales Meseguer University Hospital, 30008 Murcia, Spain
- Daniele Campa
- Department of Biology, University of Pisa, 56126 Pisa, Italy
- Víctor Moreno
- Catalan Institute of Oncology, Bellvitge Biomedical Research Institute (IDIBELL), 08908 Barcelona, Spain
- Silvia de Sanjosé
- Catalan Institute of Oncology, Bellvitge Biomedical Research Institute (IDIBELL), 08908 Barcelona, Spain
- Rafael Marcos-Gragera
- Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), University of Barcelona, 08908 Barcelona, Spain
- María García-Álvarez
- Department of Hematology, University Hospital of Salamanca (HUS/IBSAL), CIBERONC and Cancer Research Institute of Salamanca-IBMCC (USAL-CSIC), 37007 Salamanca, Spain
- Trinidad Dierssen-Sotos
- Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), University of Barcelona, 08908 Barcelona, Spain
- Andrés Jerez
- Department of Hematology, Experimental Hematology Unit, Vall d’Hebron Institute of Oncology (VHIO), University Hospital Vall d’Hebron, 08035 Barcelona, Spain
- Aleksandra Butrym
- Department of Cancer Prevention and Therapy, Medical University of Wrocław, 50-556 Wrocław, Poland
- Aaron D. Norman
- Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN 55905, USA
- Mario Luppi
- Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, AOU Policlinico, 41124 Modena, Italy
- Susan L. Slager
- Division of Computational Genomics, Mayo Clinic, Rochester, MN 85054, USA
- Kari Hemminki
- Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
- Yang Li
- Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands
- Sonja I. Berndt
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20814, USA
- Delphine Casabonne
- Catalan Institute of Oncology, Bellvitge Biomedical Research Institute (IDIBELL), 08908 Barcelona, Spain
- Miguel Alcoceba
- Department of Hematology, University Hospital of Salamanca (HUS/IBSAL), CIBERONC and Cancer Research Institute of Salamanca-IBMCC (USAL-CSIC), 37007 Salamanca, Spain
- Anna Puiggros
- Molecular Cytogenetics Laboratory, Pathology Department, Hospital del Mar, 08003 Barcelona, Spain
- Mihai G. Netea
- Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands
- Asta Försti
- Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), 69120 Heidelberg, Germany
- Federico Canzian
- Genomic Epidemiology Group, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
- Juan Sainz
- Genomic Oncology Area, GENYO, Centre for Genomics and Oncological Research: Pfizer/University of Granada/Andalusian Regional Government, PTS, 18016 Granada, Spain
- DOI
- https://doi.org/10.3390/ijms24098005
- Journal volume & issue
-
Vol. 24,
no. 9
p. 8005
Abstract
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 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.
Keywords
- chronic lymphocytic leukemia
- overall survival
- TTFT
- genetic variants
- susceptibility
- polygenic risk score
