Polygenic risk score for ulcerative colitis predicts immune checkpoint inhibitor-mediated colitis.
prospective_cohort · Level II
Where this comes from
- Record sourced from PubMed, PMID 38531883.
- Also identified by DOI 10.1038/s41467-023-44512-4 and PMC identifier 10966072.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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 (PRS<sub>CD</sub>) and UC (PRS<sub>UC</sub>) 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 PRS<sub>UC</sub> predicts all-grade IMC (OR<sub>meta</sub>=1.35 per standard deviation [SD], 95% CI = 1.12-1.64, P = 2×10<sup>-03</sup>) and severe IMC (OR<sub>meta</sub>=1.49 per SD, 95% CI = 1.18-1.88, P = 9×10<sup>-04</sup>). PRS<sub>CD</sub> is not associated with IMC. Furthermore, PRS<sub>UC</sub> predicts severe IMC among patients treated with combination ICIs (OR<sub>meta</sub>=2.20 per SD, 95% CI = 1.07-4.53, P = 0.03). Overall, PRS<sub>UC</sub> can identify patients receiving ICI at risk of developing IMC and may be useful to monitor patients and improve patient outcomes.
Medical subject headings
- Colitis, Ulcerative
- Carcinoma, Non-Small-Cell Lung
- Lung Neoplasms
- Colitis
- Crohn Disease