Lin, Wei-Yu and Fordham, Sarah E and Sunter, Nicola and Elstob, Claire and Rahman, Thahira and Willmore, Elaine and Shepherd, Colin and Strathdee, Gordon and Mainou-Fowler, Tryfonia and Piddock, Rachel and Mearns, Hannah and Barrow, Timothy and Houlston, Richard S and Marr, Helen and Wallis, Jonathan and Summerfield, Geoffrey and Marshall, Scott and Pettitt, Andrew and Pepper, Christopher and Fegan, Christopher and Forconi, Francesco and Dyer, Martin JS and Jayne, Sandrine and Sellors, April and Schuh, Anna and Robbe, Pauline and Oscier, David and Bailey, James and Rais, Syed and Bentley, Alison and Cawkwell, Lynn and Evans, Paul and Hillmen, Peter and Pratt, Guy and Allsup, David J and Allan, James M (2021) Genome-wide association study identifies risk loci for progressive chronic lymphocytic leukemia. Nature communications, 12 (1). 665-. DOI https://doi.org/10.1038/s41467-020-20822-9
Lin, Wei-Yu and Fordham, Sarah E and Sunter, Nicola and Elstob, Claire and Rahman, Thahira and Willmore, Elaine and Shepherd, Colin and Strathdee, Gordon and Mainou-Fowler, Tryfonia and Piddock, Rachel and Mearns, Hannah and Barrow, Timothy and Houlston, Richard S and Marr, Helen and Wallis, Jonathan and Summerfield, Geoffrey and Marshall, Scott and Pettitt, Andrew and Pepper, Christopher and Fegan, Christopher and Forconi, Francesco and Dyer, Martin JS and Jayne, Sandrine and Sellors, April and Schuh, Anna and Robbe, Pauline and Oscier, David and Bailey, James and Rais, Syed and Bentley, Alison and Cawkwell, Lynn and Evans, Paul and Hillmen, Peter and Pratt, Guy and Allsup, David J and Allan, James M (2021) Genome-wide association study identifies risk loci for progressive chronic lymphocytic leukemia. Nature communications, 12 (1). 665-. DOI https://doi.org/10.1038/s41467-020-20822-9
Lin, Wei-Yu and Fordham, Sarah E and Sunter, Nicola and Elstob, Claire and Rahman, Thahira and Willmore, Elaine and Shepherd, Colin and Strathdee, Gordon and Mainou-Fowler, Tryfonia and Piddock, Rachel and Mearns, Hannah and Barrow, Timothy and Houlston, Richard S and Marr, Helen and Wallis, Jonathan and Summerfield, Geoffrey and Marshall, Scott and Pettitt, Andrew and Pepper, Christopher and Fegan, Christopher and Forconi, Francesco and Dyer, Martin JS and Jayne, Sandrine and Sellors, April and Schuh, Anna and Robbe, Pauline and Oscier, David and Bailey, James and Rais, Syed and Bentley, Alison and Cawkwell, Lynn and Evans, Paul and Hillmen, Peter and Pratt, Guy and Allsup, David J and Allan, James M (2021) Genome-wide association study identifies risk loci for progressive chronic lymphocytic leukemia. Nature communications, 12 (1). 665-. DOI https://doi.org/10.1038/s41467-020-20822-9
Abstract
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<sup>-9</sup>) and 6p (rs3778076, HR = 1.99, 95% CI = 1.55-2.55; P = 5.08 × 10<sup>-8</sup>), 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Aged; Disease Progression; Female; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Kaplan-Meier Estimate; Leukemia, Lymphocytic, Chronic, B-Cell; Male; Middle Aged; Multivariate Analysis; Polymorphism, Single Nucleotide; Prognosis; Quantitative Trait Loci; cancer genetics; cancer genomics; chronic lymphocytic leukaemia; genetic markers; prognostic markers |
| Divisions: | Faculty of Science and Health Faculty of Science and Health > Life Sciences, School of |
| SWORD Depositor: | Unnamed user with email elements@essex.ac.uk |
| Depositing User: | Unnamed user with email elements@essex.ac.uk |
| Date Deposited: | 23 Aug 2024 09:12 |
| Last Modified: | 23 Aug 2024 09:12 |
| URI: | http://repository.essex.ac.uk/id/eprint/34487 |
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