Changes in DNA, also known as mutations, can cause an ordinary The development of cancer requires successive DNA changes over a long period of time along with abnormalities in specific genes, called driver genes. The presence of such a signature does not always mean that cancer is directly present.
Colibactin
Previous research showed a link between certain intestinal bacteria and DNA abnormalities that could potentially cause colon cancer. This involved a type of E. coli bacteria that damage DNA by secreting the substance colibactin. This study was led by Dr Ruben van Boxtel, research group leader at the Princess Máxima Centre and Oncode researcher, and Prof Dr Hans Clevers, pioneer in the field of organoids, former research group leader at the Princess Máxima Centre and the Hubrecht Institute, and also Oncode researcher. In the follow-up study, published today in Cancer Cell, they expand on this research.
Genetic signature
The researchers looked at the link between individual E. coli bacterial strains and a genetic signature also found in the tumour cells of colon cancer patients. To do this, they exposed colon cancer mini-tumours, also called organoids, to the different bacterial strains. They then analysed the DNA of these organoids. The researchers saw that all four E. coli strains studied caused the colon cancer signature in the organoids. This happened to varying degrees. For this, the researchers compared the strains with the signature of strain EcC, detected in the earlier study. They saw that strain 2F8 caused the most similar abnormalities: 112%. For the least harmful strain, E. coli Nissle 1917, this was 32%.
Artificial intelligence was also used to examine DNA in cells obtained from population screening and people with colon cancer. Dr Joske Ubels, postdoctoral researcher and bioinformatician in the Van Boxtel group: 'We analysed a large amount of data from over 600 different people and linked this data to the genetic signature. For example, we saw that people with DNA damage caused by colibactin are on average younger when they are diagnosed with colon cancer, 63 versus 68 years. In addition, we saw that two in 25 people (8%) with the colibactin-induced DNA signature also had a specific change in the APC gene, one of the main driver genes in colon cancer. That is almost four times more common than in the no-harm group (2%). Only when changes also occur in other driver genes colon cancer can develop.'
This underlines the researchers' earlier theory that damage by colibactin may contribute to the development of colon cancer. And that better recognition of the DNA signature provides important new insights into the factors involved in the development of cancer, such as the change in the APC driver gene.
Probiotics
The four bacteria studied included the colibactin-producing E. coli Nissle 1917 (EcN), which is used as a probiotic and prescribed as a treatment for the intestinal diseases Crohn's and colitis. Van Boxtel: 'In this study, we did not investigate the direct link between the specific bacteria and the development of colon cancer, so we did not demonstrate this. The results do indicate that colibactin can prepare a cell for transformation into a cancer cell. However, additional damage caused by other mutational processes are necessary for the development of cancer.' The researchers thus highlight the importance of carefully assessing the potential long-term consequences in relation to the short-term clinical benefits.
Future pediatric cancer research
The methods used for this study may also be applicable in future research into the development of (second) forms of cancer and thus also childhood cancer. Clevers who led the research together with Van Boxtel: 'This new study offers possibilities for possible future research into links between specific substances and the emergence of recognisable genetic signatures. After all, if we can better recognise the cause of the emergence of mutations then that is also an immediate starting point for research into a way to prevent them.'
Everyone is exposed to bacteria. They live all around you and occur on your skin and in your body. The E. coli bacteria lives in the intestines. There are many different strains. Some of them are protective and others can make you sick. Certain strains produce the chemical colibactin; about 20% of people carry bacteria of this kind. Some people use probiotics that contain E.coli. It can also be prescribed for inflammatory bowel diseases (E. coli Nissle 1917). No probiotics are prescribed at the Princess Máxima Center.