The microbiome as a colorectal cancer screening biomarker (CRCbiome)

There is a link between gut bacteria and colorectal cancer risk. This project aims to discover gut microbiota biomarkers for colorectal cancer screening, and investigate the relationship between the precursors of crc, lifestyle factors and gut bacteria.

Last updated: 9/20/2022

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 improvement to be more accurate and less costly and invasive. CRC 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 bacteria in the gut, - the 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 of 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:

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

The project have established a cohort 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.

The CRCbiome multi-omics

In a project starting up in 2022, we are integrating the data from the microbiome with epigenome, transcriptome, 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 to identify associations and correlations between epigenomic profiles of precursor lesions with clinical factors, gut microbiome and blood transcriptome biomarkers.

Design and infrastructure

The CRCbiome study have recruited participants enrolled in the Bowel Cancer Screening in Norway (BCSN) study - a pilot for the national colorectal cancer screening program. Near 3000 screening participants with a positive Fecal immunochemical (FIT) test was invited to participate in our study. Before the colonoscopy, the study participants were asked to fill in a lifestyle- and demographics questionnaire and a validated food frequency questionnaire, developed at the University of Oslo. Neoplastic lesions detected as part of the screening examination was removed during colonoscopy. Two and twelve months after the colonoscopy, the participants were asked for a new FIT test. With this it is possible to investigate whether the microbiome changes after the removal of any precursors to cancer.

Project status

The recruitment of study participants started in September 2017 and is now finished with a total of 1640 participants. The questionnaires data is completed and quality checked. The DNA extraction protocol is finished, and all the samples have been sequenced. We have established bioinformatic pipelines and started analyzing the metagenome data. In 2022 the majority of the group relocated from the Cancer Registry of Norway to the University of Oslo, Centre for Bioinformatics and the Department of Pharmacy.

Paula Istvan started as an affiliated postdoc in November 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 and is now a researcher on the project. 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. Ekaterina Avershina started as a researcher in May 2022. She will be working with tissue
epigenomics of precursor lesions. Maja Jacobsen started in May 2022 as the project coordinator and lab engineer.

Photo: The core group of the CRCbiome project.

How to get access to data

All research projects that includes information from CRCbiome must comply with the EU’s General Data Protection Regulation (GDPR). This means that the processing must have approval from the Regional Committee for Medical Research in Norway (REC). Furthermore the processing needs legal basis according to GDPR Article 6 and 9. The applicant must have considered the need for a Data Protection Impact Assessment (DPIA) according to GDPR article 35. The applicant must prove that these requirements have been met before the data can be made available. Disclosure of information to countries outside the EU requires that the conditions in GDPR are met. To apply for access to data from the CRCbiome study the applicant must fill out this form: Data access application form. For more information, or submission of the application form, email: t.b.rounge@farmasi.uio.no

List of publications

Paula Istvan, Einar Birkeland, Ekaterina Avershina, Ane S Kværner, Vahid Bemanian, Willem M. de Vos, Torbjørn Rognes, Paula Berstad, Trine B Rounge. Exploring the gut virome in fecal immunochemical test stool samples reveals novel associations with lifestyle in a large population-based study. medRxiv 2023.08.24.23294548; doi: https://doi.org/10.1101/2023.08.24.23294548

Birkeland E, Ferrero G, Pardini B, Umu SU, Tarallo S, Bulfamante S, Hoff G, Senore C, Rounge TB, Naccarati A. Profiling small RNAs in fecal immunochemical tests: is it possible? Mol Cancer. 2023 Oct 3;22(1):161. doi: 10.1186/s12943-023-01869-w. PMID: 37789383; PMCID: PMC10546694.

Kvaerner AS, Andersen AR, Henriksen HB, Knudsen MD, Johansen AMW, Hjartåker A, Bøhn SK, Paur I, Wiedswang G, Smeland S, Rounge TB, Blomhoff R, Berstad P. Associations of the 2018 World Cancer Research Fund/American Institute of Cancer Research (WCRF/AICR) cancer prevention recommendations with stages of colorectal carcinogenesis. Cancer Med. 2023 Jul;12(13):14806-14819. doi: 10.1002/cam4.6119. Epub 2023 May 22. PMID: 37212529; PMCID: PMC10358192.

Bucher-Johannessen C, Birkeland EE, Vinberg E, Bemanian V, Hoff G, Berstad P, Rounge TB. Long-term follow-up of colorectal cancer screening attendees identifies differences in Phascolarctobacterium spp. using 16S rRNA and metagenome sequencing. Front Oncol. 2023 Apr 27;13:1183039. doi: 10.3389/fonc.2023.1183039. PMID: 37182146; PMCID: PMC10172651.

Kværner AS, Birkeland E, Vinberg E, Hoff G, Hjartåker A, Rounge TB, Berstad P. Associations of red and processed meat intake with screen-detected colorectal lesions. Br J Nutr. 2022 Sep 7;129(12):1-11. doi: 10.1017/S0007114522002860. Epub ahead of print. PMID: 36069337; PMCID: PMC10197083.

Kværner AS, Birkeland E, Bucher-Johannessen C, Vinberg E, Nordby JI, Kangas H, Bemanian V, Ellonen P, Botteri E, Natvig E, Rognes T, Hovig E, Lyle R, Ambur OH, de Vos WM, Bultman S, Hjartåker A, Landberg R, Song M, Blix HS, Ursin G, Randel KR, de Lange T, Hoff G, Holme Ø, Berstad P, Rounge TB. The CRCbiome study: a large prospective cohort study examining the role of lifestyle and the gut microbiome in colorectal cancer screening participants. BMC Cancer. 2021 Aug 18;21(1):930. doi: 10.1186/s12885-021-08640-8. PMID: 34407780; PMCID: PMC8371800.

Rounge TB, Meisal R, Nordby JI, Ambur OH, de Lange T, Hoff G. Evaluating gut microbiota profiles from archived fecal samples. BMC Gastroenterol. 2018 Nov 8;18(1):171. doi: 10.1186/s12876-018-0896-6. PMID: 30409123; PMCID: PMC6225565.

Associated master projects

Flere masterstudenter har brukt og bruker data fra prosjektet.

Ongoing projects

Lisi Zhan – Identification of pks+ bacterial genomes in CRCbiome – starter januar 2023

Vladimir Zarić – Prescription drug use in colorectal cancer screening participants – starter august 2023

Cassandra Hjortdahl – Microbiome prediction of lifestyle factors – starter august 2023

Sandra Therese Olsen Bratlie – Antimicrobial use and the gut microbiome in colorectal cancer screening participants – starter august 2023

Completed projects

Arfa Irej Qureshi – The Mycobiome – fullført 2023

Jenny Fjørtoft – Regional differences in the microbiome – fullført 2023

Frøya Berg Grønvik – Intake of dairy products and advanced neoplasia – fullført 2023

Simon N Barak – VIRMAKE: a Snakemake workflow for viral identification of metagenomic sequence data – fullført 2023

Ignas Rumbavicius – Tool to remove specific organisms from microbiome sequencing data: Host Contamination Removal Tool (HoCoRT) (https://github.com/ignasrum/hocort/) – fullført 2022

Monica Linnea Dahlgren – Intake of NOVA classified processed foods at different stages of colorectal carcinogenesis: A cross-sectional investigation among Norwegian adults - fullført 2022

Emilie Syse Jalland – Identification of participants in need of colonoscopy in a FIT-positive screening population with the use of diet and lifestyle factors - fullført 2022

Henrik Olsvik – Developing a pipeline for deep analysis of cancer causing genes in the gut microbiome – fullført 2021

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

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