Genome-wide association study identifies risk loci for progressive chronic lymphocytic leukemia.

Autor: Lin WY; Translational and Clinical Research Institute, Newcastle University Centre for Cancer, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK., Fordham SE; Translational and Clinical Research Institute, Newcastle University Centre for Cancer, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK., Sunter N; Translational and Clinical Research Institute, Newcastle University Centre for Cancer, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK., Elstob C; Translational and Clinical Research Institute, Newcastle University Centre for Cancer, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK., Rahman T; Translational and Clinical Research Institute, Newcastle University Centre for Cancer, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK., Willmore E; Translational and Clinical Research Institute, Newcastle University Centre for Cancer, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK., Shepherd C; Translational and Clinical Research Institute, Newcastle University Centre for Cancer, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK., Strathdee G; Translational and Clinical Research Institute, Newcastle University Centre for Cancer, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK., Mainou-Fowler T; Translational and Clinical Research Institute, Newcastle University Centre for Cancer, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK., Piddock R; Translational and Clinical Research Institute, Newcastle University Centre for Cancer, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK., Mearns H; Translational and Clinical Research Institute, Newcastle University Centre for Cancer, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK., Barrow T; Faculty of Health Sciences and Wellbeing, University of Sunderland, Sunderland, UK., Houlston RS; Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK., Marr H; Department of Haematology, Freeman Hospital, Newcastle upon Tyne, UK., Wallis J; Department of Haematology, Freeman Hospital, Newcastle upon Tyne, UK., Summerfield G; Queen Elizabeth Hospital, Gateshead, UK., Marshall S; City Hospitals Sunderland NHS Trust, Sunderland, UK., Pettitt A; University of Liverpool, Liverpool, UK., Pepper C; Brighton and Sussex Medical School, University of Sussex, Brighton, UK., Fegan C; Institute of Cancer and Genetics, School of Medicine, Cardiff University, Cardiff, UK., Forconi F; Cancer Sciences Unit, Cancer Research UK and NIHR Experimental Cancer Medicine Centres, University of Southampton, Southampton, UK., Dyer MJS; The Ernest and Helen Scott Haematological Research Institute, Leicester Cancer Research Centre, University of Leicester, Leicester, UK., Jayne S; The Ernest and Helen Scott Haematological Research Institute, Leicester Cancer Research Centre, University of Leicester, Leicester, UK., Sellors A; The Ernest and Helen Scott Haematological Research Institute, Leicester Cancer Research Centre, University of Leicester, Leicester, UK., Schuh A; University of Oxford, Oxford, UK., Robbe P; University of Oxford, Oxford, UK., Oscier D; Royal Bournemouth Hospital, Bournemouth, UK., Bailey J; Hull University Teaching Hospital NHS Trust, Hull, UK., Rais S; Hull University Teaching Hospital NHS Trust, Hull, UK., Bentley A; Centre for Atherothrombosis and Metabolic Disease, Hull York Medical School, Hull, UK., Cawkwell L; University of Hull, Hull, UK., Evans P; Haematological Malignancy Diagnostic Service Laboratory, St James' Institute of Oncology, Leeds, UK., Hillmen P; Section of Experimental Haematology, Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, UK., Pratt G; University of Birmingham, Birmingham, UK., Allsup DJ; Hull University Teaching Hospital NHS Trust, Hull, UK. hycda1@hyms.ac.uk.; Centre for Atherothrombosis and Metabolic Disease, Hull York Medical School, Hull, UK. hycda1@hyms.ac.uk., Allan JM; Translational and Clinical Research Institute, Newcastle University Centre for Cancer, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK. james.allan@newcastle.ac.uk.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2021 Jan 28; Vol. 12 (1), pp. 665. Date of Electronic Publication: 2021 Jan 28.
DOI: 10.1038/s41467-020-20822-9
Abstrakt: Prognostication in patients with chronic lymphocytic leukemia (CLL) is challenging due to heterogeneity in clinical course. We hypothesize that constitutional genetic variation affects disease progression and could aid prognostication. Pooling data from seven studies incorporating 842 cases identifies two genomic locations associated with time from diagnosis to treatment, including 10q26.13 (rs736456, hazard ratio (HR) = 1.78, 95% confidence interval (CI) = 1.47-2.15; P = 2.71 × 10 -9 ) and 6p (rs3778076, HR = 1.99, 95% CI = 1.55-2.55; P = 5.08 × 10 -8 ), which are particularly powerful prognostic markers in patients with early stage CLL otherwise characterized by low-risk features. Expression quantitative trait loci analysis identifies putative functional genes implicated in modulating B-cell receptor or innate immune responses, key pathways in CLL pathogenesis. In this work we identify rs736456 and rs3778076 as prognostic in CLL, demonstrating that disease progression is determined by constitutional genetic variation as well as known somatic drivers.
Databáze: MEDLINE