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

Author

Listed:
  • Wei-Yu Lin

    (Newcastle University)

  • Sarah E. Fordham

    (Newcastle University)

  • Nicola Sunter

    (Newcastle University)

  • Claire Elstob

    (Newcastle University)

  • Thahira Rahman

    (Newcastle University)

  • Elaine Willmore

    (Newcastle University)

  • Colin Shepherd

    (Newcastle University)

  • Gordon Strathdee

    (Newcastle University)

  • Tryfonia Mainou-Fowler

    (Newcastle University)

  • Rachel Piddock

    (Newcastle University)

  • Hannah Mearns

    (Newcastle University)

  • Timothy Barrow

    (University of Sunderland)

  • Richard S. Houlston

    (The Institute of Cancer Research)

  • Helen Marr

    (Freeman Hospital)

  • Jonathan Wallis

    (Freeman Hospital)

  • Geoffrey Summerfield

    (Queen Elizabeth Hospital)

  • Scott Marshall

    (City Hospitals Sunderland NHS Trust)

  • Andrew Pettitt

    (University of Liverpool)

  • Christopher Pepper

    (University of Sussex)

  • Christopher Fegan

    (Cardiff University)

  • Francesco Forconi

    (University of Southampton)

  • Martin J. S. Dyer

    (University of Leicester)

  • Sandrine Jayne

    (University of Leicester)

  • April Sellors

    (University of Leicester)

  • Anna Schuh

    (University of Oxford)

  • Pauline Robbe

    (University of Oxford)

  • David Oscier

    (Royal Bournemouth Hospital)

  • James Bailey

    (Hull University Teaching Hospital NHS Trust)

  • Syed Rais

    (Hull University Teaching Hospital NHS Trust)

  • Alison Bentley

    (Hull York Medical School)

  • Lynn Cawkwell

    (University of Hull)

  • Paul Evans

    (St James’ Institute of Oncology)

  • Peter Hillmen

    (Leeds Institute of Medical Research at St James’s, University of Leeds)

  • Guy Pratt

    (University of Birmingham)

  • David J. Allsup

    (Hull University Teaching Hospital NHS Trust
    Hull York Medical School)

  • James M. Allan

    (Newcastle University)

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.

Suggested Citation

  • Wei-Yu Lin & Sarah E. Fordham & Nicola Sunter & Claire Elstob & Thahira Rahman & Elaine Willmore & Colin Shepherd & Gordon Strathdee & Tryfonia Mainou-Fowler & Rachel Piddock & Hannah Mearns & Timothy, 2021. "Genome-wide association study identifies risk loci for progressive chronic lymphocytic leukemia," Nature Communications, Nature, vol. 12(1), pages 1-8, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-020-20822-9
    DOI: 10.1038/s41467-020-20822-9
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