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

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ICR Authors

Houlston, Richard

Authors

Lin, W-Y
Fordham, SE
Sunter, N
Elstob, C
Rahman, T
Willmore, E
Shepherd, C
Strathdee, G
Mainou-Fowler, T
Piddock, R
Mearns, H
Barrow, T
Houlston, RS
Marr, H
Wallis, J
Summerfield, G
Marshall, S
Pettitt, A
Pepper, C
Fegan, C
Forconi, F
Dyer, MJS
Jayne, S
Sellors, A
Schuh, A
Robbe, P
Oscier, D
Bailey, J
Rais, S
Bentley, A
Cawkwell, L
Evans, P
Hillmen, P
Pratt, G
Allsup, DJ
Allan, JM

Document Type

Journal Article

Date

2021-01-28

Date Accepted

2020-12-16

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 × 10-9) 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.

Citation

Nature communications, 2021, 12 (1), pp. 665 - ?

DOI

10.1038/s41467-020-20822-9

URI

https://repository.icr.ac.uk/handle/internal/4365

Rights

https://creativecommons.org/licenses/by/4.0

Source Title

Publisher

NATURE PORTFOLIO

ISSN

2041-1723

eISSN

2041-1723

Collections

Genetics and Epidemiology

Research Team

Cancer Genomics
Cancer Genomics

Notes