The Scent of Lynch Syndrome

National multicentre prospective trial evaluating the use of faecal/urinal VOCs, faecal microbiota, faecal amino acids and faecal protein profiles as markers for detection of colorectal neoplasia in patients with Lynch syndrome. In addition, we will explore the microbial signature in these patients.
Patients will fill in questionnaires and stool and urine samples will be collected. VOCs from patients with CRC and/or adenoma(s) detected at surveillance colonoscopy (performed 2-yearly as part of routine care), will be compared to subjects without CRC and adenomas by using an electronic nose (GC-IMS). Faecal microbial composition, amino acids and protein profiles will be analysed using 16 S rRNA amplicon sequencing or (shotgun) metagenomic analysis, High Performance Liquid Chromatography (HPLC) and LC-MS/MS, respectively.

We hypothesize that VOCs hold potential as a non-invasive screening tool for detection of colorectal neoplastic lesions in Lynch syndrome. Faecal composition of microbiota as well as amino acids and proteins might be other potential non-invasive biomarkers for CRC and adenoma. Potentially, timing of endoscopy could be guided by non-invasive biomarkers in future.
Lastly, patients with Lynch syndrome may harbour an aberrant or different colonic microbiome, that might contribute to the elevated risk of developing colorectal cancer.

Patients will be asked to collect stool samples at inclusion and then 6-monthly during a two-year period (5 samples). This will include a sample 1 – 4
weeks prior to colonoscopy and three months after colonoscopy. Some patients will also collect urine samples at the same set times. Additionally, Patients will complete a questionnaire on the day of sample collection. Biannual colonoscopy will be performed as part of the routine surveillance program.

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