The CRCbiome study: a large prospective cohort study examining the role of lifestyle and the gut microbiome in colorectal cancer screening participants

Ane Sørlie Kværner,Trine B Rounge,Torbjørn Rognes,Anette Hjartåker,Øyvind Holme,Harri Kangas,Cecilie Bucher-Johannessen,Thomas De Lange,Geir Hoff,Mingyang Song,Willem M De Vos,Edoardo Botteri,Paula Berstad,Erik Natvig,Kristin Ranheim Randel,Vahid Bemanian,Hege Salvesen Blix,Jan Inge Nordby,Scott J Bultman ,Rikard Landberg,Pekka Ellonen,Robert Lyle,Elina Vinberg,Even Birkeland ,Ole Herman Ambur,Eivind Hovig,Giske Ursin

doi:10.1186/s12885-021-08640-8

Abstract

BackgroundColorectal cancer (CRC) screening reduces CRC incidence and mortality. However, current screening methods are either hampered by invasiveness or suboptimal performance, limiting their effectiveness as primary screening methods. To aid in the development of a non-invasive screening test with improved sensitivity and specificity, we have initiated a prospective biomarker study (CRCbiome), nested within a large randomized CRC screening trial in Norway. We aim to develop a microbiome-based classification algorithm to identify advanced colorectal lesions in screening participants testing positive for an immunochemical fecal occult blood test (FIT). We will also examine interactions with host factors, diet, lifestyle and prescription drugs. The prospective nature of the study also enables the analysis of changes in the gut microbiome following the removal of precancerous lesions.MethodsThe CRCbiome study recruits participants enrolled in the Bowel Cancer Screening in Norway (BCSN) study, a randomized trial initiated in 2012 comparing once-only sigmoidoscopy to repeated biennial FIT, where women and men aged 50–74 years at study entry are invited to participate. Since 2017, participants randomized to FIT screening with a positive test result have been invited to join the CRCbiome study. Self-reported diet, lifestyle and demographic data are collected prior to colonoscopy after the positive FIT-test (baseline). Screening data, including colonoscopy findings are obtained from the BCSN database. Fecal samples for gut microbiome analyses are collected both before and 2 and 12 months after colonoscopy. Samples are analyzed using metagenome sequencing, with taxonomy profiles, and gene and pathway content as primary measures. CRCbiome data will also be linked to national registries to obtain information on prescription histories and cancer relevant outcomes occurring during the 10 year follow-up period.DiscussionThe CRCbiome study will increase our understanding of how the gut microbiome, in combination with lifestyle and environmental factors, influences the early stages of colorectal carcinogenesis. This knowledge will be crucial to develop microbiome-based screening tools for CRC. By evaluating biomarker performance in a screening setting, using samples from the target population, the generalizability of the findings to future screening cohorts is likely to be high.Trial registrationClinicalTrials.gov Identifier: NCT01538550.

Highlights

Colorectal cancer (CRC) screening reduces CRC incidence and mortality
Study design The CRCbiome study is a prospective cohort study nested within the Bowel Cancer Screening in Norway (BCSN) trial, which is a pilot for a national screening program, organized by the Cancer Registry of Norway
Numbers will add up to 100% bPolyps lost during colonoscopy or where the endoscopist considers biopsy unnescessary, for example hyperplastic polyps in the rectum cIncludes hyperplastic polyps with size < 10 mm and sessile serrated lesions without dysplasia and size < 10 mm dDefined as any serrated lesions with size ≥ 10 mm or dysplasia eDefined as any adenoma with either villous histology (≥25% villous components), high-grade dysplasia or polyp size greater than or equal to 10 mm [52] fDefined as presence of adenocarcinoma arising from the colon or rectum

Summary

Introduction

Colorectal cancer (CRC) screening reduces CRC incidence and mortality. The significant contribution to global cancer deaths, together with the worrying rise in incidence rates seen globally [3], especially the recent increase among younger age groups [6, 7], highlights the need for widespread prevention strategies that are both effective and feasible on a large-scale basis. The progression of precursor lesions to CRC is a long-term process, spanning a period of 10–15 years for most lesions [9]. During this long latency period, most cancers develop asymptomatically, making them difficult to detect at a preclinical stage. International guidelines recommend screening, with the aim of detection and removal of precancerous lesions to prevent cancer from occurring, or to detect cancer at the earliest stage possible [10,11,12,13]

Objectives

Methods

Findings

Discussion

Conclusion