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

Journal

medRxiv : the preprint server for health sciences
Titre abrégé: medRxiv
Pays: United States
ID NLM: 101767986

Informations de publication

Date de publication:
13 Sep 2023
Historique:
pubmed: 9 6 2023
medline: 9 6 2023
entrez: 9 6 2023
Statut: epublish

Résumé

Immune checkpoint inhibitors (ICIs) are a remarkable advancement in cancer therapeutics; however, a substantial proportion of patients develop severe immune-related adverse events (irAEs). Understanding and predicting irAEs is a key to advancing precision immuno-oncology. Immune checkpoint inhibitor-mediated colitis (IMC) is a significant complication from ICI and can have life-threatening consequences. Based on clinical presentation, IMC mimics inflammatory bowel disease, however the link is poorly understood. We hypothesized that genetic susceptibility to Crohn's disease (CD) and ulcerative colitis (UC) may predispose to IMC. We developed and validated polygenic risk scores for CD (PRS

Identifiants

DOI: 10.1101/2023.05.15.23289680 PMID: 37292751 PMC: PMC10246037
pubmed: 37292751
doi: 10.1101/2023.05.15.23289680
pmc: PMC10246037
pii:
doi:

Types de publication

Preprint

Langues

eng

Subventions

Organisme : NIH HHS
ID : S10 OD017985
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000445
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA227466
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA009207
Pays : United States
Organisme : NHLBI NIH HHS
ID : U19 HL065962
Pays : United States
Organisme : NCRR NIH HHS
ID : S10 RR025141
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA251758
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NCI NIH HHS
ID : UG1 CA233259
Pays : United States
Organisme : NICHD NIH HHS
ID : R01 HD074711
Pays : United States
Organisme : NIGMS NIH HHS
ID : RC2 GM092618
Pays : United States
Organisme : NIGMS NIH HHS
ID : P50 GM115305
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA068485
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG006378
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG004798
Pays : United States
Organisme : NCI NIH HHS
ID : K24 CA169004
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA129243
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA253560
Pays : United States
Organisme : NCRR NIH HHS
ID : UL1 RR024975
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS032830
Pays : United States

Auteurs

Pooja Middha (P)

Department of Medicine, University of California San Francisco, San Francisco, CA, USA.

Rohit Thummalapalli (R)

Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.

Michael J Betti (MJ)

Department of Medicine, Division of Genetic Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.

Lydia Yao (L)

Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA.

Zoe Quandt (Z)

Division of Endocrinology and Metabolism, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
Diabetes Center, University of California San Francisco, San Francisco, CA, USA.

Karmugi Balaratnam (K)

Princess Margaret Cancer Centre, Toronto, ON, Canada.

Cosmin A Bejan (CA)

Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN, USA.

Eduardo Cardenas (E)

Department of Medicine, University of California San Francisco, San Francisco, CA, USA.

Christina J Falcon (CJ)

Fiona and Stanley Druckenmiller Center for Lung Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

David M Faleck (DM)

Gastroenterology, Hepatology & Nutrition Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Matthew A Gubens (MA)

Medical Oncology, University of California San Francisco, San Francisco, CA, USA.
Department of Medicine, Weill Cornell Medical Center, New York, NY, USA.

Scott Huntsman (S)

Department of Medicine, University of California San Francisco, San Francisco, CA, USA.

Douglas B Johnson (DB)

Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.

Linda Kachuri (L)

Department of Epidemiology and Population Health, Stanford University School of Medicine, Stanford, CA, USA.
Stanford Cancer Institute, Stanford University of Medicine, Stanford, CA, USA.

Khaleeq Khan (K)

Princess Margaret Cancer Centre, Toronto, ON, Canada.

Min Li (M)

Department of Medicine, University of California San Francisco, San Francisco, CA, USA.

Christine M Lovly (CM)

Department of Medicine, Division of Hematology and Oncology, Vanderbilt University Medical Center and Vanderbilt Ingram Cancer Center, Nashville, TN, USA.

Megan H Murray (MH)

Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA.

Devalben Patel (D)

Princess Margaret Cancer Centre, Toronto, ON, Canada.

Kristin Werking (K)

Department of Thoracic Surgery, Vanderbilt University Medical Center, Nashville, TN, USA.

Yaomin Xu (Y)

Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA.

Luna Jia Zhan (LJ)

Princess Margaret Cancer Centre, Toronto, ON, Canada.

Justin M Balko (JM)

Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.

Geoffrey Liu (G)

Princess Margaret Cancer Centre, Temerty School of Medicine, Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada.

Melinda C Aldrich (MC)

Department of Medicine, Division of Genetic Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.

Adam J Schoenfeld (AJ)

Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, New York, New York.

Elad Ziv (E)

Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
Helen Diller Family Comprehensive Cancer Center, Center for Genes, Environment and Health and Institute for Human Genetics, University of California San Francisco, San Francisco, California.

Classifications MeSH