Genome-wide association study identifies risk loci for progressive chronic lymphocytic leukemia
Autor: | Colin Shepherd, Nicola J. Sunter, Paul G. Evans, Rachel Piddock, David Allsup, Helen Marr, Scott Marshall, Claire Elstob, Francesco Forconi, Richard S. Houlston, Syed Ashar Rais, Tryfonia Mainou-Fowler, Thahira Rahman, April Sellors, Chris Pepper, Sandrine Jayne, Alison Bentley, Sarah E. Fordham, Christopher Fegan, Anna Schuh, Peter Hillmen, Martin J. S. Dyer, David Oscier, Wei-Yu Lin, James M. Allan, Lynn Cawkwell, Jonathan P. Wallis, Guy Pratt, James R. Bailey, Geoffrey Summerfield, Andrew R. Pettitt, Gordon Strathdee, Elaine Willmore, Hannah Mearns, Pauline Robbe, Timothy M. Barrow |
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Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Oncology Male medicine.medical_specialty Chronic lymphocytic leukaemia Chronic lymphocytic leukemia Science Quantitative Trait Loci General Physics and Astronomy Genome-wide association study Kaplan-Meier Estimate Polymorphism Single Nucleotide General Biochemistry Genetics and Molecular Biology Article Pathogenesis 03 medical and health sciences Prognostic markers 0302 clinical medicine Polymorphism (computer science) immune system diseases Internal medicine hemic and lymphatic diseases Genetic variation Cancer genomics Medicine Humans Genetic Predisposition to Disease Cancer genetics Aged Multidisciplinary business.industry Hazard ratio General Chemistry Middle Aged medicine.disease Prognosis Leukemia Lymphocytic Chronic B-Cell Leukemia 030104 developmental biology 030220 oncology & carcinogenesis Expression quantitative trait loci Multivariate Analysis Disease Progression Genetic markers Female business Genome-Wide Association Study |
Zdroj: | Nature Communications Nature Communications, Vol 12, Iss 1, Pp 1-8 (2021) |
ISSN: | 2041-1723 |
Popis: | 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. The clinical course of chronic lymphocytic leukaemia (CLL) is variable and difficult to predict. Here, the authors conduct a genome wide association study meta-analysis for time to first treatment in CLL patients and report two loci associating with progressive disease. |
Databáze: | OpenAIRE |
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