A Gut Microbiome-based Diagnostic Tool for the Screening of Colorectal Cancer

Colorectal cancer (CRC) is the 3rd most common cancer and the 2nd most common cause of cancer death worldwide, with nearly 2 million new cases and one million deaths in 2020. In the last decades, a population-based screening programs for average-risk populations have established as an effective strategy to reduce both incidence and mortality of CRC through early detection of cancer. The fecal immunochemical testing (FIT), the reference diagnostic tool in most countries, has still a suboptimal diagnostic yield, with both missed adenomas and, mainly, unnecessary colonoscopies. For these reasons, in the last years the identification of novel, non-invasive biomarkers is absolutely advocatein the field of CRC. A large body of evidence shows that alterations of the gut microbiome and the enrichment of specific taxa (e.g. Fusobacterium nucleatum, Parvimonas micra, and others) are involved in the pathogenesis of CRC. Moreover, recent studies, including metagenomic meta-analyses from our group, have discovered common microbial signatures able to reproducibly discriminate between patients with CRC and healthy controls. Based on this evidence, international guidelines have recently advocated the exploitation of microbiome-based biomarkers for the screening of CRC in clinical practice, but such studies are not yet available to date.

The primary objective is to develop a gut microbiome-based diagnostic tool for the identification of CRC and advanced colorectal adenomas.

The secondary objectives are:

• To associate FIT with clinical and colonoscopy outcomes
• To characterize gut microbiome of enrolled patients
• To associate microbiome signatures with clinical and colonoscopy outcomes. This is an observational prospective multicenter study, in which patients will be selected among those enrolled in the national colorectal cancer (CRC) screening program and among who refer to all centers involved in this study for screening colonoscopy. Patients with all inclusion criteria and none of the exclusion criteria (detailed in the specific section of this website) will be considered for this study.N=1202 patients will be enrolled, based on sample size calculation and including a validation group. N=911 patients will be needed, and we will add 91 patients to cover a 10% potential drop-out and 200 patients as a validation group (20% of the study cohort). Patients enrolled in this validation cohort will have the same exclusion and inclusion criteria of other patients and will undergo the same study procedures. At baseline all enrolled patients will provide a fecal sample (collected using a buffer for genome preservation) within 2 weeks from enrollment and will be stored at -80°C at each clinical center and assigned de-identified IDs. Moreover demographic, clinical characteristics and laboratory data will be recorded.

For all enrolled patients clinicians will record the following data: