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Polygenic risk score for ulcerative colitis predicts immune checkpoint inhibitor-mediated colitis

Author

Listed:
  • Pooja Middha

    (University of California San Francisco)

  • Rohit Thummalapalli

    (Memorial Sloan Kettering Cancer Center)

  • Michael J. Betti

    (Vanderbilt University Medical Center)

  • Lydia Yao

    (Vanderbilt University Medical Center)

  • Zoe Quandt

    (University of California San Francisco
    University of California San Francisco)

  • Karmugi Balaratnam

    (Princess Margaret Cancer Centre)

  • Cosmin A. Bejan

    (Vanderbilt University Medical Center)

  • Eduardo Cardenas

    (University of California San Francisco)

  • Christina J. Falcon

    (Fiona and Stanley Druckenmiller Center for Lung Cancer Research, Memorial Sloan Kettering Cancer Center)

  • David M. Faleck

    (Memorial Sloan Kettering Cancer Center)

  • Matthew A. Gubens

    (University of California San Francisco
    University of California San Francisco)

  • Scott Huntsman

    (University of California San Francisco)

  • Douglas B. Johnson

    (Vanderbilt University Medical Center)

  • Linda Kachuri

    (Stanford University School of Medicine
    Stanford University of Medicine)

  • Khaleeq Khan

    (Princess Margaret Cancer Centre)

  • Min Li

    (University of California San Francisco)

  • Christine M. Lovly

    (Vanderbilt University Medical Center and Vanderbilt Ingram Cancer Center)

  • Megan H. Murray

    (Vanderbilt University Medical Center)

  • Devalben Patel

    (Princess Margaret Cancer Centre)

  • Kristin Werking

    (Vanderbilt University Medical Center)

  • Yaomin Xu

    (Vanderbilt University Medical Center)

  • Luna Jia Zhan

    (Princess Margaret Cancer Centre)

  • Justin M. Balko

    (Vanderbilt University Medical Center)

  • Geoffrey Liu

    (Princess Margaret Cancer Centre
    Temerty School of Medicine
    University of Toronto)

  • Melinda C. Aldrich

    (Vanderbilt University Medical Center)

  • Adam J. Schoenfeld

    (Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center)

  • Elad Ziv

    (University of California San Francisco
    University of California San Francisco
    University of California San Francisco
    University of California San Francisco)

Abstract

Immune checkpoint inhibitor-mediated colitis (IMC) is a common adverse event of treatment with immune checkpoint inhibitors (ICI). We hypothesize that genetic susceptibility to Crohn’s disease (CD) and ulcerative colitis (UC) predisposes to IMC. In this study, we first develop a polygenic risk scores for CD (PRSCD) and UC (PRSUC) in cancer-free individuals and then test these PRSs on IMC in a cohort of 1316 patients with ICI-treated non-small cell lung cancer and perform a replication in 873 ICI-treated pan-cancer patients. In a meta-analysis, the PRSUC predicts all-grade IMC (ORmeta=1.35 per standard deviation [SD], 95% CI = 1.12–1.64, P = 2×10−03) and severe IMC (ORmeta=1.49 per SD, 95% CI = 1.18–1.88, P = 9×10−04). PRSCD is not associated with IMC. Furthermore, PRSUC predicts severe IMC among patients treated with combination ICIs (ORmeta=2.20 per SD, 95% CI = 1.07–4.53, P = 0.03). Overall, PRSUC can identify patients receiving ICI at risk of developing IMC and may be useful to monitor patients and improve patient outcomes.

Suggested Citation

  • Pooja Middha & Rohit Thummalapalli & Michael J. Betti & Lydia Yao & Zoe Quandt & Karmugi Balaratnam & Cosmin A. Bejan & Eduardo Cardenas & Christina J. Falcon & David M. Faleck & Matthew A. Gubens & S, 2024. "Polygenic risk score for ulcerative colitis predicts immune checkpoint inhibitor-mediated colitis," Nature Communications, Nature, vol. 15(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-023-44512-4
    DOI: 10.1038/s41467-023-44512-4
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