Related Experiment Video
Updated: Jun 29, 2025
06:24
Author Spotlight: Liujunzi Decoction as a Traditional Chinese Treatment for Coloproctitis Cancer
Published on: October 13, 2023
883
Polygenic risk score for ulcerative colitis predicts immune checkpoint inhibitor-mediated colitis
Pooja Middha1, Rohit Thummalapalli2, Michael J Betti3
1Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
Nature Communications
|March 27, 2024
Summary
Genetic susceptibility to ulcerative colitis (UC), measured by polygenic risk scores (PRS_UC), predicts immune checkpoint inhibitor-mediated colitis (IMC) in cancer patients. This finding may help identify individuals at higher risk for developing IMC during immunotherapy.
Area of Science:
- Oncology
- Immunology
- Genetics
Background:
- Immune checkpoint inhibitors (ICIs) can cause immune checkpoint inhibitor-mediated colitis (IMC), a frequent adverse event.
- Genetic predisposition to inflammatory bowel diseases like Crohn's disease (CD) and ulcerative colitis (UC) may influence IMC risk.
Approach:
- Developed polygenic risk scores for CD (PRS_CD) and UC (PRS_UC) in cancer-free individuals.
- Validated PRS_CD and PRS_UC in cohorts of ICI-treated non-small cell lung cancer (n=1316) and pan-cancer patients (n=873).
- Conducted meta-analysis to assess the predictive value of PRS for IMC development.
Key Points:
- Polygenic risk score for UC (PRS_UC) significantly predicts all-grade and severe IMC.
- PRS_UC demonstrated a stronger association with severe IMC in patients receiving combination ICIs.
- Polygenic risk score for CD (PRS_CD) showed no association with IMC.
Conclusions:
- PRS_UC can identify patients receiving ICI therapy who are at increased risk of developing IMC.
- Utilizing PRS_UC may aid in patient monitoring and potentially improve outcomes for patients undergoing ICI treatment.
Related Concept Videos
01:27Inflammatory Bowel Disease I: Ulcerative Colitis
179
Introduction
Inflammatory bowel disease, or IBD, encompasses a group of disorders characterized by chronic inflammation or ulceration of the gastrointestinal tract.
Risk Factors
The exact cause of IBD remains unclear, although it is believed to be due to a mix of genetic, environmental, microbial, and immune factors. Genetic factors are significant in determining susceptibility to IBD, with family history being a critical risk factor. Individuals with a first-degree relative who has IBD are at...
Inflammatory bowel disease, or IBD, encompasses a group of disorders characterized by chronic inflammation or ulceration of the gastrointestinal tract.
Risk Factors
The exact cause of IBD remains unclear, although it is believed to be due to a mix of genetic, environmental, microbial, and immune factors. Genetic factors are significant in determining susceptibility to IBD, with family history being a critical risk factor. Individuals with a first-degree relative who has IBD are at...
179
01:29Drugs for Treatment of Ulcerative Colitis in IBD
138
Ulcerative colitis is a chronic inflammatory condition primarily affecting the colon and rectum. The primary drugs used in the treatment of ulcerative colitis are aminosalicylates. They exhibit anti-inflammatory and immunosuppressive properties. They modulate inflammatory mediators and inhibit the activity of nuclear factor κB (NF-κB). Aminosalicylates also reduce inflammation by inhibiting prostaglandin and leukotriene production and decreasing neutrophil chemotaxis and superoxide...
138
01:30Inflammatory Bowel Disease III: Diagnostic Studies and Management I-Nutritional Therapy
331
Various diagnostic tests are employed in the diagnostic process for Inflammatory Bowel Disease (IBD), particularly to differentiate between Crohn's disease and ulcerative colitis.
Diagnostic studies
A colonoscopy is the definitive screening test, distinguishing ulcerative colitis from other colon diseases with similar symptoms. During a colonoscopy test, inflamed mucosa with exudate ulcerations can be observed, and biopsies are taken to determine the histologic characteristics of the...
Diagnostic studies
A colonoscopy is the definitive screening test, distinguishing ulcerative colitis from other colon diseases with similar symptoms. During a colonoscopy test, inflamed mucosa with exudate ulcerations can be observed, and biopsies are taken to determine the histologic characteristics of the...
331
01:30Peptic Ulcer Disease I: Introduction
168
Peptic Ulcer Disease (PUD) is characterized by mucosal excavation in the esophagus, stomach, pylorus, or duodenum. It can manifest as acute or chronic based on the extent and duration of mucosal involvement.
An acute ulcer, marked by superficial erosion and minimal inflammation, swiftly resolves upon identifying and addressing the underlying cause. In contrast, a chronic ulcer persists, potentially eroding through the muscular wall and forming fibrous tissue.
Peptic ulcers can also be...
An acute ulcer, marked by superficial erosion and minimal inflammation, swiftly resolves upon identifying and addressing the underlying cause. In contrast, a chronic ulcer persists, potentially eroding through the muscular wall and forming fibrous tissue.
Peptic ulcers can also be...
168
01:29Drugs for Treatment of Crohn's Disease in IBD Using Immunomodulatory Agents
162
Crohn's disease is an inflammatory bowel disorder marked by chronic inflammation of the GI tract. Various treatment strategies for Crohn's disease are employed, such as immunomodulatory agents, glucocorticoids, and biologics or anti-TNF therapy. Azathioprine (Imuran), a commonly used immunomodulatory drug for Crohn's disease, is converted in the body to mercaptopurine, which inhibits purine biosynthesis and cell proliferation. Both are utilized in severe cases of Inflammatory Bowel...
162
01:30Inflammatory Bowel Disease II: Crohn's Disease
233
Introduction
Inflammatory bowel disease, commonly known as IBD, refers to a collection of disorders that lead to persistent inflammation of the gastrointestinal tract. The two types of IBD are ulcerative colitis, which impacts the colon, and Crohn's disease, which can involve any part of the gastrointestinal segment.
Crohn's disease
Crohn's disease is a chronic, systemic inflammatory bowel disease (IBD) that predominantly affects the gastrointestinal tract. It is marked by...
Inflammatory bowel disease, commonly known as IBD, refers to a collection of disorders that lead to persistent inflammation of the gastrointestinal tract. The two types of IBD are ulcerative colitis, which impacts the colon, and Crohn's disease, which can involve any part of the gastrointestinal segment.
Crohn's disease
Crohn's disease is a chronic, systemic inflammatory bowel disease (IBD) that predominantly affects the gastrointestinal tract. It is marked by...
233