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.
Ability to provide written informed consent and comply with study procedures
Reside in the Lisbon Metropolitan Area,, Portugal
Age from 40 to 74 years
Age < 40 years or ≥ 75 years
Unable to provide informed consent
Refusal to provide stool samples
Active oncological disease
Two different recruiting strategies will be used: * Opportunistic recruitment: recruitment will be conducted in collaboration with the gastroenterology and general medicine departments of partner hospitals in Lisbon. Eligible individuals scheduled for a screening colonoscopy will be informed about the study by an on-site study coordinator. Those willing to participate will sign an informed consent form. * Random recruitment: interested individuals can access detailed information and assess their eligibility by completing an online questionnaire on the study's website. Eligible participants can register and provide informed consent digitally. After registration, participants will be contacted to arrange the delivery of a self-collection kit for stool sample collection.
Case-control
Prospective
No intervention: observational study
Other interventionNo intervention: observational study
Microbiome biomarkers associated with CRC and/or high-risk polyps.
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
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.
Effect of diet on CRC risk and gut microbiota composition
Dietary intake will be assessed via telephone interview through two 24-hour recalls, following the protocol validated by the European Food Safety Authority (EFSA).
Effect of the Mediterranean Diet on CRC risk and gut microbiota composition
Adherence to the Mediterranean Diet will be assessed using the PREvención con DIeta MEDiterránea (PREDIMED) nutritional questionnaire, a validated 14-item tool. Each question is scored either 0 (condition not met) or 1 (condition met), resulting in a total score ranging from 0 to 14 (7). Based on this final score, adherence to the Mediterranean Diet will then be categorised into three groups: low adherence (score \< 5), moderate adherence (score 6-9), and high adherence (score \> 10)
Effect of physical activity on CRC risk and gut microbiota composition
Physical activity will be assessed using the Nordic Physical Activity Questionnaire-short form, a validated tool composed of two close-ended questions for monitoring adherence to WHO physical activity recommendations. Participants will be categorized as "Below WHO physical activity recommendations" or "Equal to WHO physical activity recommendations"
Effect of sleeping habits on CRC risk and gut microbiota composition
Sleeping habits will be assessed by the Pittsburgh Sleep Quality Index (PSQI), a validated questionnaire that consists of 19 items which are distributed into seven "components": subjective sleep quality; sleep latency; sleep duration; habitual sleep efficiency; sleep disturbances; use of sleeping medication; day-time dysfunction. Each component is scored from 0 a 2, and the sum of the component scores yields a global PSQI score. A global PSQI score ≥6 will indicate poor sleep quality.
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Gulbenkian Institute for Molecular Medicine
Lead sponsor
Hospital CUF Descobertas, Lisbon, Portugal
Collaborator
CUF Tejo Hospital
Collaborator
Hospital da Luz Lisboa, Portugal
Collaborator
