The CRCbiome study: a large prospective cohort study examining the role of lifestyle and the gut microbiome in colorectal cancer screening participants
Journal article, 2021
Background: Colorectal 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.
Methods: The 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.
Discussion: The 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 registration: ClinicalTrials.gov Identifier: NCT01538550.
Prescription drugs
Diet
Advanced neoplasia
Colorectal cancer
FIT
Adenoma
Metagenomics sequencing
Lifestyle
Gut microbiome
Screening
Biomarkers
Colonoscopy
iFOBT
Author
Ane Sørlie Kværner
Cancer Registry of Norway Institute of Population-Based Cancer Research
Einar Birkeland
Cancer Registry of Norway Institute of Population-Based Cancer Research
Cecilie Bucher-Johannessen
Cancer Registry of Norway Institute of Population-Based Cancer Research
Rikshospitalet-Radiumhospitalet HF
Elina Vinberg
Cancer Registry of Norway Institute of Population-Based Cancer Research
Jan Inge Nordby
Oslo University Hospital
Harri Kangas
University of Helsinki
Vahid Bemanian
Akershus University Hospital
Pekka Ellonen
University of Helsinki
Edoardo Botteri
Cancer Registry of Norway Institute of Population-Based Cancer Research
Erik Natvig
Cancer Registry of Norway Institute of Population-Based Cancer Research
Torbjørn Rognes
Oslo University Hospital
University of Oslo
Eivind Hovig
Rikshospitalet-Radiumhospitalet HF
University of Oslo
Robert Lyle
Oslo University Hospital
Norwegian Institute of Public Health
Ole Herman Ambur
Akershus University Hospital
Oslo Metropolitan University
Willem M. de Vos
Wageningen University and Research
University of Helsinki
Scott Bultman
The University of North Carolina System
Anette Hjartåker
University of Oslo
Rikard Landberg
Chalmers, Biology and Biological Engineering, Food and Nutrition Science
Mingyang Song
Massachusetts General Hospital
Harvard School of Public Health
Hege Salvesen Blix
Norwegian Institute of Public Health
University of Oslo
Giske Ursin
Cancer Registry of Norway Institute of Population-Based Cancer Research
Kristin Ranheim Randel
Cancer Registry of Norway Institute of Population-Based Cancer Research
Thomas de Lange
Sahlgrenska University Hospital
Sykehuset Asker og Bærum
University of Gothenburg
Geir Hoff
Cancer Registry of Norway Institute of Population-Based Cancer Research
Sykehuset Telemark
Øyvind Holme
Sørlandet Hospital Kristiansand
University of Oslo
Cancer Registry of Norway Institute of Population-Based Cancer Research
Paula Berstad
Cancer Registry of Norway Institute of Population-Based Cancer Research
Trine B. Rounge
University of Oslo
Cancer Registry of Norway Institute of Population-Based Cancer Research
BMC Cancer
14712407 (eISSN)
Vol. 21 1 930Subject Categories
General Practice
Public Health, Global Health, Social Medicine and Epidemiology
Cancer and Oncology
DOI
10.1186/s12885-021-08640-8
PubMed
34407780