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,
Einar Birkeland,
Cecilie Bucher-Johannessen,
Elina Vinberg,
Jan Inge Nordby,
Harri Kangas,
Vahid Bemanian,
Pekka Ellonen,
Edoardo Botteri,
Erik Natvig,
Torbjørn Rognes,
Eivind Hovig,
Robert Lyle,
Ole Herman Ambur,
Willem M. de Vos,
Scott Bultman,
Anette Hjartåker,
Rikard Landberg,
Mingyang Song,
Hege Salvesen Blix,
Giske Ursin,
Kristin Ranheim Randel,
Thomas de Lange,
Geir Hoff,
Øyvind Holme,
Paula Berstad,
Trine B. Rounge
Affiliations
Ane Sørlie Kværner
Section for Colorectal Cancer Screening, Cancer Registry of Norway
Einar Birkeland
Department of Research, Cancer Registry of Norway
Cecilie Bucher-Johannessen
Department of Research, Cancer Registry of Norway
Elina Vinberg
Department of Research, Cancer Registry of Norway
Jan Inge Nordby
Department of Medical Biochemistry, Oslo University Hospital
Harri Kangas
Institute for Molecular Medicine Finland, HiLIFE, University of Helsinki
Vahid Bemanian
Department of Multidisciplinary Laboratory Science and Medical Biochemistry, Genetic Unit, Akershus University Hospital
Pekka Ellonen
Institute for Molecular Medicine Finland, HiLIFE, University of Helsinki
Edoardo Botteri
Section for Colorectal Cancer Screening, Cancer Registry of Norway
Erik Natvig
Section for Colorectal Cancer Screening, Cancer Registry of Norway
Torbjørn Rognes
Department of Informatics, Centre for Bioinformatics, University of Oslo
Eivind Hovig
Department of Tumor Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital
Robert Lyle
Department of Medical Genetics, Oslo University Hospital and University of Oslo
Ole Herman Ambur
Department of Microbiology and Infection Control, Akershus University Hospital
Willem M. de Vos
Laboratory of Microbiology, Wageningen University
Scott Bultman
Department of Genetics and Lineberger Comprehensive Cancer Center, University of North Carolina
Anette Hjartåker
Department of Nutrition, University of Oslo
Rikard Landberg
Department of Biology and Biological Engineering, Division of Food and Nutrition Science, Chalmers University of Technology
Mingyang Song
Department of Epidemiology, Harvard T.H. Chan School of Public Health
Hege Salvesen Blix
Department of Drug Statistics, Norwegian Institute of Public Health
Giske Ursin
Cancer Registry of Norway
Kristin Ranheim Randel
Section for Colorectal Cancer Screening, Cancer Registry of Norway
Thomas de Lange
Medical Department, Sahlgrenska University Hospital-Mölndal
Geir Hoff
Section for Colorectal Cancer Screening, Cancer Registry of Norway
Øyvind Holme
Section for Colorectal Cancer Screening, Cancer Registry of Norway
Paula Berstad
Section for Colorectal Cancer Screening, Cancer Registry of Norway
Abstract 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 .
