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

  1. Middha, Pooja ORCID logo
  2. Thummalapalli, Rohit
  3. Betti, Michael ORCID logo
  4. Yao, Lydia
  5. Quandt, Zoe
  6. Balaratnam, Karmugi
  7. Bejan, Cosmin ORCID logo
  8. Cardenas, Eduardo
  9. Falcon, Christina J.
  10. Faleck, David M.
  11. Princess Margaret Lung Group
  12. Gubens, Matthew A.
  13. Huntsman, Scott
  14. Johnson, Douglas ORCID logo
  15. Kachuri, Linda ORCID logo
  16. Khan, Kaleeq
  17. Li, Min
  18. Lovly, Christine ORCID logo
  19. Murray, Megan H ORCID logo
  20. Patel, Devalben
  21. Werking, Kristin
  22. Xu, Yaomin
  23. Zhan, Luna Jia
  24. Balko, Justin ORCID logo
  25. Liu, Geoffrey
  26. Aldrich, Melinda ORCID logo
  27. Schoenfeld, Adam ORCID logo
  28. Ziv, Elad ORCID logo

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1000 Titel
  • Polygenic risk score for ulcerative colitis predicts immune checkpoint inhibitor-mediated colitis
1000 Autor/in
  1. Middha, Pooja |
  2. Thummalapalli, Rohit |
  3. Betti, Michael |
  4. Yao, Lydia |
  5. Quandt, Zoe |
  6. Balaratnam, Karmugi |
  7. Bejan, Cosmin |
  8. Cardenas, Eduardo |
  9. Falcon, Christina J. |
  10. Faleck, David M. |
  11. Princess Margaret Lung Group |
  12. Gubens, Matthew A. |
  13. Huntsman, Scott |
  14. Johnson, Douglas |
  15. Kachuri, Linda |
  16. Khan, Kaleeq |
  17. Li, Min |
  18. Lovly, Christine |
  19. Murray, Megan H |
  20. Patel, Devalben |
  21. Werking, Kristin |
  22. Xu, Yaomin |
  23. Zhan, Luna Jia |
  24. Balko, Justin |
  25. Liu, Geoffrey |
  26. Aldrich, Melinda |
  27. Schoenfeld, Adam |
  28. Ziv, Elad |
1000 Erscheinungsjahr 2024
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2024-03-26
1000 Erschienen in
1000 Quellenangabe
  • 15(1):2568
1000 Copyrightjahr
  • 2024
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.1038/s41467-023-44512-4 |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10966072/ |
1000 Ergänzendes Material
  • https://www.nature.com/articles/s41467-023-44512-4#Sec23 |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • 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.
1000 Sacherschließung
lokal Cancer genetics
lokal Cancer epidemiology
lokal Non-small-cell lung cancer
lokal Outcomes research
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
  1. https://orcid.org/0000-0001-5503-8215|https://frl.publisso.de/adhoc/uri/VGh1bW1hbGFwYWxsaSwgUm9oaXQ=|https://orcid.org/0000-0001-8394-6202|https://frl.publisso.de/adhoc/uri/WWFvLCBMeWRpYQ==|https://frl.publisso.de/adhoc/uri/UXVhbmR0LCBab2U=|https://frl.publisso.de/adhoc/uri/QmFsYXJhdG5hbSwgS2FybXVnaQ==|https://orcid.org/0000-0001-5107-0584|https://frl.publisso.de/adhoc/uri/Q2FyZGVuYXMsIEVkdWFyZG8=|https://frl.publisso.de/adhoc/uri/RmFsY29uLCBDaHJpc3RpbmEgSi4=|https://frl.publisso.de/adhoc/uri/RmFsZWNrLCBEYXZpZCBNLg==|https://frl.publisso.de/adhoc/uri/UHJpbmNlc3MgTWFyZ2FyZXQgTHVuZyBHcm91cA==|https://frl.publisso.de/adhoc/uri/R3ViZW5zLCBNYXR0aGV3IEEu|https://frl.publisso.de/adhoc/uri/SHVudHNtYW4sIFNjb3R0|https://orcid.org/0000-0002-6390-773X|https://orcid.org/0000-0002-3226-4727|https://frl.publisso.de/adhoc/uri/S2hhbiwgS2FsZWVx|https://frl.publisso.de/adhoc/uri/TGksIE1pbg==|https://orcid.org/0000-0002-3641-6361|https://orcid.org/0000-0002-0131-2626|https://frl.publisso.de/adhoc/uri/UGF0ZWwsIERldmFsYmVu|https://frl.publisso.de/adhoc/uri/V2Vya2luZywgS3Jpc3Rpbg==|https://frl.publisso.de/adhoc/uri/WHUsIFlhb21pbg==|https://frl.publisso.de/adhoc/uri/WmhhbiwgTHVuYSBKaWE=|https://orcid.org/0000-0002-4263-5974|https://frl.publisso.de/adhoc/uri/TGl1LCBHZW9mZnJleQ==|https://orcid.org/0000-0003-3833-8448|https://orcid.org/0000-0002-2644-1416|https://orcid.org/0000-0002-2324-2884
1000 Label
1000 Förderer
  1. National Institutes of Health |
  2. Vanderbilt Institute for Clinical and Translational Research |
  3. National Institute of Diabetes and Digestive and Kidney Diseases |
  4. Larry L. Hillblom Foundation |
  5. Memorial Sloan-Kettering Cancer Center |
1000 Fördernummer
  1. R01-CA227466; K24-CA169004; NIH NCI UG1CA233259; P01CA129243; P30CA068485; T32-CA009207; U01CA253560; R01CA251758; NIH/NCI R01CA227481; NIH/NHLBI R01HL156021
  2. UL1TR002243
  3. K12DK133995
  4. -
  5. P30-CA008748
1000 Förderprogramm
  1. -
  2. -
  3. DiabDocs
  4. Start-Up Grant
  5. Support Grant
1000 Dateien
1000 Förderung
  1. 1000 joinedFunding-child
    1000 Förderer National Institutes of Health |
    1000 Förderprogramm -
    1000 Fördernummer R01-CA227466; K24-CA169004; NIH NCI UG1CA233259; P01CA129243; P30CA068485; T32-CA009207; U01CA253560; R01CA251758; NIH/NCI R01CA227481; NIH/NHLBI R01HL156021
  2. 1000 joinedFunding-child
    1000 Förderer Vanderbilt Institute for Clinical and Translational Research |
    1000 Förderprogramm -
    1000 Fördernummer UL1TR002243
  3. 1000 joinedFunding-child
    1000 Förderer National Institute of Diabetes and Digestive and Kidney Diseases |
    1000 Förderprogramm DiabDocs
    1000 Fördernummer K12DK133995
  4. 1000 joinedFunding-child
    1000 Förderer Larry L. Hillblom Foundation |
    1000 Förderprogramm Start-Up Grant
    1000 Fördernummer -
  5. 1000 joinedFunding-child
    1000 Förderer Memorial Sloan-Kettering Cancer Center |
    1000 Förderprogramm Support Grant
    1000 Fördernummer P30-CA008748
1000 Objektart article
1000 Beschrieben durch
1000 @id frl:6473905.rdf
1000 Erstellt am 2024-03-27T14:38:01.539+0100
1000 Erstellt von 284
1000 beschreibt frl:6473905
1000 Bearbeitet von 317
1000 Zuletzt bearbeitet Tue Apr 02 09:39:17 CEST 2024
1000 Objekt bearb. Tue Apr 02 09:38:59 CEST 2024
1000 Vgl. frl:6473905
1000 Oai Id
  1. oai:frl.publisso.de:frl:6473905 |
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