Improving Colorectal Cancer Early Screening in Portugal: Identification and Validation of Biomarkers of Gut Microbiome in Stool
Trial Snapshot
- Phase
- Not Applicable
- Status
- Recruiting
- Sponsor
- Enrollment
- 30,000
- Locations
- 2
- Primary Endpoint
- Microbiome biomarkers associated with CRC and/or high-risk polyps.
Study Overview
Brief Summary
Colorectal cancer (CRC) is a major public health problem, responsible for 2 million new cases and almost 1 million deaths annually worldwide. In Portugal, as of 2022, CRC is the most common cancer, with 10,575 new cases reported, and the second leading cause of cancer-related mortality, accounting for 4,809 deaths (approximately 14% of all cancer-related deaths). In recent years, there has been an alarming increase in the incidence and mortality of CRC in people <50 years of age.
Early detection is crucial, as survival rates decline sharply from 90% when detected early to just 10% in advanced stages. Non-invasive diagnostic tests, such as the Faecal Immunochemical Test (FIT), have a low sensitivity for early-stage lesions and a high rate of false positives. Therefore, there is an urgent need to improve non-invasive diagnostic methods for the early detection of CRC, as effective screening can prevent it by detecting and removing premalignant lesions.
Recent studies suggest that an altered gut microbiota may confer susceptibility to certain types of cancer. Interestingly, the gut microbiota of patients with adenomas or CRC differs from that of healthy individuals. This study aims to identify gut microbiome biomarkers in faecal samples associated with CRC and/or high-risk adenomas to improve early detection.
Detailed Description
This study will analyse the gut microbiome in stool samples collected from individuals living in the Lisbon Metropolitan Area, Portugal. Using shotgun metagenomics, the investigators aim to identify microbiome biomarkers associated with the early detection of CRC and the progression of precancerous lesions (adenomas). The identified biomarkers will be tested to develop a non-invasive and highly sensitive screening tool for CRC and precancerous lesions.
Primary Objective:
To identify gut microbiome biomarkers in faecal DNA associated with CRC and/or high-risk adenomas.
Secondary Objectives:
i) Establish the correlation between FIT results, faecal microbiome testing and colonoscopy results.
Study Design
- Study Type
- Observational
- Observational Model
- Case Control
- Time Perspective
- Prospective
Eligibility Criteria
- Ages
- 40 Years to 74 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Ability to provide written informed consent and comply with study procedures
- •Reside in the Lisbon Metropolitan Area,, Portugal
- •Age from 40 to 74 years
Exclusion Criteria
- •Age < 40 years or ≥ 75 years
- •Unable to provide informed consent
- •Refusal to provide stool samples
- •Active oncological disease
- •Personal history of CRC
- •Personal history of colon adenomas removed in the last 24 months
- •First-degree family history of CRC
- •Previous diagnosis of inflammatory bowel disease (ulcerative colitis, Crohn's disease or indeterminate colitis), inflammatory bowel syndrome, persistent and infectious gastroenteritis, colitis or gastritis, persistent or chronic diarrhoea of unknown aetiology or recurrent infection by Clostridioides difficile
- •Severe cardiovascular or heart diseases with medical diagnosis
- •Severe renal failure requiring hemodialysis
- •Severe lung disease
- •Pregnancy
Outcomes
Primary Outcomes
Microbiome biomarkers associated with CRC and/or high-risk polyps.
Time Frame: Baseline and Follow-up every 2 years up to 6 years
The faecal microbiota composition and gene profiles will be analysed using shotgun metagenomic sequencing on a subset of participants (up to 10,000 samples). Data will be integrated with lifestyle, dietary factors and colonoscopy results to identify biomarkers linked to CRC and adenomas.
Correlation between microbiome biomarkers and FIT results
Time Frame: Baseline and Follow-up every 2 years up to 6 years
Faecal microbiome analysis results will be compared with FIT test results to evaluate the predictive value, negative predictive value, and overall effectiveness in detecting CRC in an asymptomatic population.
Secondary Outcomes
- Effect of the Mediterranean Diet on CRC risk and gut microbiota composition(Baseline)
- Effect of physical activity on CRC risk and gut microbiota composition(Baseline)
- Effect of sleeping habits on CRC risk and gut microbiota composition(Baseline)
- Effect of diet on CRC risk and gut microbiota composition(Baseline)
- Effect of stress levels on CRC risk and gut microbiota composition(Baseline)
- Risk factors (medical history, lifestyle and dietary habits) associated with CRC and/or high-risk polyps(Baseline and Follow-up every 2 years up to 6 years)