Oncobiome – Microbiome and Cancer
Since most microbiome research so far has focused on the microbiome of the lower gut and stomach, many of us at CTMR have a long-standing interest in cancer of the gastro-intestinal tract. We have been at the frontline of Helicobacter pylori research since the 1980s, when H. pylori has been linked to gastric ulcers and gastric cancer. H. pyloriis actually one of the first established pathogens classified as a carcinogen according to the World Health Organisation. Yet, with the rapid advancements in the microbiome field, there is increasing evidence that the microbiome composition (incl. bacterial and viral pathogens and previously considered commensals) may also affect the risk of cancer, the prognosis and the response to treatment. Therefore, at CTMR we explore the association of the gut, vaginal and oral microbiome with different types of cancers, including yet not restricting to colon, breast and cervical cancer.
Some of the questions we aim to answer:
- What is a healthy microbiome composition?
- Is the microbiome different in individuals with (pre-) cancer compared to healthy individuals?
- Can we use the microbiome to predict who is most likely to have or develop cancer?
- Which factors are interacting in this microbiome-cancer association, including prescribed drug use (e.g. antibiotics, proton pump inhibitors), hormonal factors (sex differences), diet and other clinical and demographic characteristics?
- Which cancer treatments do affect the microbiome, and which microbiome compositions lead to a higher treatment success and better prognosis?
- Can we change the microbiome to improve treatment efficacy and prognosis?
Our translational approach is based on large clinical cohorts, as obtained through the Swedish Nationwide colorectal screening program (Screening of Swedish Colons, SCREESCO, Principal Investigator: Senior Professor Rolf Hultcrantz) and population-based registry-based studies using the excellent Swedish Health Registries which can also be linked to our clinical cohorts. For these studies we have ongoing collaborations within Karolinska Institutet, nationally (including Jönköping University) and internationally.
CTMR is also one of the core participants of the ongoing ONCOBIOME project (Funded by the European Union through the Horizon2020 framework), under the lead of Professor Lars Engstrand, and project coordinator Associate Professor Nele Brusselaers. This ONCOBIOME collaboration between 17 collaborators aims to explore the role of the microbiome in cancer, from early detection and diagnosis to treatment and prognosis.
ONCOBIOME (version 10 MAY 2019)
Two research groups at Karolinska Institutet are involved in the ONCOBIOME project:
- Prof Lars Engstrand and colleagues from the Centre for Translational Microbiome Research (CTMR) (Prof. Lars Engstrand and co), Dept. Microbiology, Tumour and Cell Biology
- Prof Janne Lehtiö and colleagues from the Lehtiö Lab, Dept. Oncology and Pathology.
At CTMR we are working on a large randomised controlled trial to assess different screening methods for colorectal cancer, initiated by Professor Rolf Hultcrantz, and enrolling study participants during 2014-2019. One of the arms of this trial, including approximately 30,000 individuals, uses the Faecal Immunochemistry Test (FIT) used to detect blood in the faeces, which can also be used for the assessment of the gut microbiome. If blood was detected in the test, the individual received a colonoscopy, and we can thereby compare the microbiome composition between a selection of the healthy individuals (with false positive tests), those with premalignant laesions, and those with colorectal cancer. We are further preparing for linkages with the national Swedish Health Registries, to follow-up all cohort members for occurrence of melanoma,lung cancer or breast cancer. Main people involved: Prof. Lars Engstrand (Principal Investigator), Assoc. Prof. Nele Brusselaers (Project Coordinator, Clinical Epidemiologist), Assoc. Prof. Katja Fall (Clinical Epidemiologist).
The Lehtiö group is currently involved in building the system which will host the clinical and sequencing repository for more than 9500 cancer patients in 16 European centres, namely the central ONCOBIOBE Database (CO-DB). As in any software development project, we started gathering information about the data and the required functionalities. We were able to get an initial agreement with the help of the University of Turin regarding the patient ID format which is composed of 25 characters and sample ID format which is composed of 26 characters. We will also offer an optional sample id so that partners who use barcodes or any other kind of ids can use them. University of Turin will provide us with the algorithm to encrypt and decrypt all IDs before storing them in the database and labelling the samples.
Next step will be to gather information from all parties regarding patient and sample metadata in details, namely their data types and their sizes. In addition, we will investigate the security requirements of all parties and what the different user roles are that the system will have. When all information is available we will provide a proposal for the required system and request feedback on it from all our partners. When the gathering information stage is completed, we can define the hardware and software specifications and start the development stage. Main people currently involved: Prof Janne Lehtiö, Dr. Maan Rachid, Dr. Helena Backväll (Project Manager), Dr. Jorrit Boekel.