The microbiome as a colorectal cancer screening biomarker (CRCbiome)

Presence of certain bacteria in the gut are strongly associated with colorectal cancer. This project aims to discover gut microbiota biomarkers for colorectal cancer screening.
Last updated: 3/18/2022

Background

Colorectal cancer (CRC) symptoms are unspecific - often emerging when the disease is no longer curable. Screening reduces CRC mortality, but current screening tests need improvment to be more accurate and less costly and invasive.

Presence of certain bacteria in the gut are strongly associated with CRC. It is now possible to investigate all bacteria in the gut, - the microbiota, for its role in initiation and progression of colorectal cancer in large epidemiological studies and hence discover disease biomarkers.

Colorectal cancer is one of the cancer types with strongest association with lifestyle, and there is reason to believe that this association is partly mediated trough the gut microbiota. 

We are investigating interactions between CRC, lifestyle and microbiota to better guide prevention of CRC and increase the biomarker performance.

Project Aims

The overall aim om the CRCbiome study is to discover gut microbiota biomarkers for colorectal cancer screening. To reach the overall aim we have defined the following sub-aims:

  1. Identify associations of the gut microbiome with advanced neoplasia, defined as presence of advanced adenoma or CRC
  2. Examine interactions of the gut microbiome with host factors, diet, lifestyle and medication use on advanced neoplasia risk
  3. Describe modifications of the gut microbiome following removal of precursor lesions of CRC

The project is establishing a cohort including including a biobank with fecal samples and biopsies, lifestyle information and data from national health registries for use in future studies. Read more about the study design and data in the cohort paper. 

Design and infrastructure

The project takes advantage of the established infrastructure in the BCSN-trial, and near 3000 screening participants  with a positive Fecal immunochemical (FIT) test will be invited to participate in our study. Before the colonoscopy, we will ask the study participant to fill in a lifestyle- and demographics questionnaire and a validated food frequency questionnaire, developed at the University of Oslo. Two and twelve months after the colonoscopy, we will ask the participants for a new FIT test, to analyse the microbiota.  

                                                              

Project status

The recruitment of study participants started in September 2017 and is now finished with a total of 1640 participants. The DNA extraction protocol is finished, and the last samples are queued for sequencing. We have established bioinformatic pipelines and started analysing the metagenome data. The lifestyle questionnaires data is completed and are being quality checked. 

Paula Istvan started as an affiliated postdoc in October 2020. She studies the FIT virome and the effect of the extra hygienic measures adopted during this current pandemic on the gut microbiota. Einar Birkeland started as a postdoc in March 2020. He works with the metagenome analyses. Cecilie Bucher-Johannessen started as PhD student in March 2020. She investigates sex differences in gut microbiota and CRC and interactions with antibiotic use. Ane Sørlie Kværner started as a postdoc in August 2019. She works with lifestyle and diet analyses. Several master students are using the project data. Three master’s theses with the project data are now completed.

The CRCbiome multi-omics

In a project starting up in 2022, we are integrating the data from the microbiome with epigenome, trancriptome, clinical and lifestyle data from study participants, aiming to improve the understanding of CRC carcinogenesis. We are taking an in-depth look at the extended gut microbiome, including bacteria, viruses, phages, fungi and their interactions and how this interplay relates to colorectal cancer. We will also investigate the epigenome of tissue samples removed during colonoscopy and how this relates to the microbiome in a colorectal cancer screening setting. 

Publications

Kværner ASBirkeland EBucher-Johannessen CVinberg ENordby JIKangas HBemanian VEllonen PBotteri ENatvig ERognes THovig ELyle RAmbur OHde Vos WMBultman SHjartåker ALandberg RSong MBlix HSUrsin GRandel KRde Lange THoff GHolme Ø, Berstad P, Rounge TB (2021).
The CRCbiome study: a large prospective cohort study examining the role of lifestyle and the gut microbiome in colorectal cancer screening participants
BMC Cancer. DOI 10.1186/s12885-021-08640-8

 

Master projects

Arfa Irej Qureshi – The Mycobiome – starting August 2022 

Jenny Fjørtoft – Regional differences in the microbiome - starting August 2022 

Monica Linnea DahlgrenIntake of NOVA classified processed foods at different stages of colorectal carcinogenesis: A cross-sectional investigation among Norwegian adults – to be completed in 2022 

Emilie Syse JallandIdentification of participants in need of colonoscopy in a FIT-positive screening population with the use of diet and lifestyle factors - to be completed in 2022

Henrik Olsvik – Machine learning pipeline for metagenome analyses – completed 2021 

Astrid Riseth Andersen - Associations of the WCRF/AICR recommendations with stages of colorectal carcinogenesis: A cross-sectional investigation among Norwegian adults – completed 2021 

Jonas Evensen Thy - Association Between Dietary Fibre Intake, Faecal Microbiome Alpha-Diversity and Colorectal Neoplasia – completed 2020