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

   


Authors: Middha, P.; Thummalapalli, R.; Betti, M. J.; Yao, L.; Quandt, Z.; Balaratnam, K.; Bejan, C. A.; Cardenas, E.; Falcon, C. J.; Faleck, D. M.; Princess Margaret Lung Group; Gubens, M. A.; Huntsman, S.; Johnson, D. B.; Kachuri, L.; Khan, K.; Li, M.; Lovly, C. M.; Murray, M. H.; Patel, D.; Werking, K.; Xu, Y.; Zhan, L. J.; Balko, J. M.; Liu, G.; Aldrich, M. C.; Schoenfeld, A. J.; Ziv, E.
Article Title: Polygenic risk score for ulcerative colitis predicts immune checkpoint inhibitor-mediated colitis
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. © The Author(s) 2024.
Journal Title: Nature Communications
Volume: 15
ISSN: 2041-1723
Publisher: Nature Publishing Group  
Date Published: 2024-01-01
Start Page: 2568
Language: English
DOI: 10.1038/s41467-023-44512-4
PROVIDER: scopus
PMCID: PMC10966072
PUBMED: 38531883
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85188567933&doi=10.1038%2fs41467-023-44512-4&partnerID=40&md5=28a968e62c47e5136bf1a39226b5e979
Notes: The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PubMed record and PDF -- Source: Scopus
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MSK Authors
  1. Adam Jacob Schoenfeld
    133 Schoenfeld
  2. David M. Faleck
    51 Faleck
  3. Christina Jade Falcon
    44 Falcon
  4. Rohit Thummalapalli
    23 Thummalapalli
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