Appendectomy and Colorectal Cancer

Altered Gut Microbiome Composition by Appendectomy Contributes to Colorectal Cancer

Colorectal cancer (CRC) is one of the most common cancer worldwide. Initiation and progression of CRC involve complex interactions among genetic, epigenetic and environmental factors. Given that hereditary and familial CRC only accounts for 2% to 5% of cases, environmental factors are the key triggers of CRC. Emerging evidence has indicated that gut microbes are an important environmental factor promoting CRC development. Gut dysbiosis has been shown to promote colorectal carcinogenesis in mice. Several individual bacterial species, such as the enterotoxigenic Bacteroides fragilis (ETBF), Fusobacterium nucleatum and Peptostreptococcus anaerobius, could exert carcinogenic effects by inducing direct DNA damage, oxidative damage and activating oncogenic signaling pathways. Recent studies have shown that the appendix plays an important role in maintaining homeostasis and biodiversity of gut microbiome by providing an ideal ecological niche for commensal bacteria and production of immunoglobulin A. Considering the key role of microorganisms in gastrointestinal pathophysiology, absence of appendix may result in disruption of microbiome homeostasis, which could potentially influence the risk of developing CRC. In terms of epidemiological evidence, the association of appendectomy with the risk of CRC development has been controversial, and to date no consensus has been attained. Although gut microorganisms could be a crucial pivot between appendectomy and risk of subsequent CRC development, the direct contribution of appendectomy and the underlying mechanisms are still largely unexplored. In this study, we aim to study

1. the association between appendectomy and colorectal cancer, and
2. the role of appendectomy in CRC risk through causing gut microbial dysbiosis.

Study Overview

• Status: Active, not recruiting
• Conditions: Colorectal Cancer; Appendicitis

• Study Type: Observational
• Enrollment (Actual): 180000

Contacts and Locations

Study Locations

• Hong Kong
  • Sha Tin, Hong Kong, 00000
    • Institute of Digestive Disease, The Chinese University of Hong Kong

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

60000 appendectomy cases and 120000 controls

Description

Inclusion Criteria:

• Individuals underwent appendectomy from January 2000 to December 2020

Exclusion Criteria:

1. patients with the age ≤18 years at enrollment;
2. Patients with any malignant diseases or inflammatory bowel disease history before enrollment;
3. Patients with hereditary syndromes of colorectal adenomas or polyps (familial adenomatous polyposis, Lynch syndrome, etc.);
4. Patients that underwent appendectomy for appendiceal neoplasms.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Non-appendectomy controls
Appendectomy cases

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Appendectomy is associated with risk of subsequent CRC incidence	Individuals underwent appendectomy from January 2000 to December 2020 will be retrieved from a population-based database (CDARS) in Hong Kong. For the control group, individuals without appendectomy between 2000 and 2020 based on the same exclusion criteria will be identified from the total population register of CDARS. For each case of appendectomy, we will select two matched referential individuals from the pool based on the year of birth and gender to study the association between appendectomy and CRC risk.	3 years

Collaborators and Investigators

• Sponsor: Chinese University of Hong Kong

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2022
• Primary Completion (Estimated): May 31, 2025
• Study Completion (Estimated): May 31, 2025

Study Registration Dates

• First Submitted: October 8, 2023
• First Submitted That Met QC Criteria: October 14, 2023
• First Posted (Actual): October 19, 2023

Study Record Updates

• Last Update Posted (Actual): October 19, 2023
• Last Update Submitted That Met QC Criteria: October 14, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Infections; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Cecal Diseases; Intraabdominal Infections; Colorectal Neoplasms; Appendicitis
• Other Study ID Numbers: 2022.203

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No