A research team from Duke-NUS Medical School has uncovered the new knowledge that colibactin, a bacterial protein derived from intestinal Escherichia coli, is a source of cancer-causing DNA mutation. However, an initial analysis shows that colibactin-induced cancers may be preventable.
A research team led by Dr Arnoud Boot, Senior Research Fellow at the Duke-NUS’ Cancer and Stem Cell Biology (CSCB) programme recently discovered the link between certain types of cancers and the toxic compound, colibactin, derived from a specific strain of intestinal Escherichia coli (E.coli). The results of their study were published in Gastroenterology and Genome Research and can provide insights of how cancers arise. This study provides scientists and medical professionals with a deeper understanding of cancer development and progression and can aid in improving cancer treatment and even prevention.
Research and genetic profiling of DNA mutations contribute to the current knowledge pool on the differences between cancer and non-cancer cells and improve the understanding of cancer progression. This research study by the Duke-NUS CSCB team hopes to add new knowledge to the current list of 65 known cancer-causing mutations in Asian patients specifically. They believe that there are still some uncommon DNA mutations to be unveiled and studied.
A total of 872 colorectal lesions from 201 polyposis patients with no prior family history of polyposis were examined. Polyposis is a condition where intestinal polyps develop, which can subsequently lead to cancer. It arises because of a mutation in the Adenomatous polyposis coli (APC) gene, which is important for normal cellular functioning. The APC gene is also a tumour suppressor gene responsible for suppressing the uncontrolled proliferation of cells in healthy cells and thus prevents the development of cancer. The research team discovered that of the patients with mutated APC gene and hence cancerous tumours, close to 20 percent of them had disease progression similar to that caused by colibactin, a toxic protein produced by a specific strain of intestinal E. coli. Hence, the team speculated that colibactin plays a role in polyp formation in these patients.
This study was based upon an earlier research in which genetic analysis of DNA mutations in 36 patients of Asian descent, who sought treatment in Singapore for oral squamous cell carcinoma, a cancer of the mouth was performed.
According to Dr Arnoud Boot, the lead author of the study, “We found a very specific pattern of DNA mutations in the oral cancer of patients who also had severe bacterial infection in their mouth. We found that these DNA mutations had been caused by a toxin called colibactin, which is produced by these bacteria.”
As colibactin is a protein produced by a specific strain of E. coli, which usually populate the intestines, it is not possible to block the contact between human cells and colibactin entirely. However, from the studies of the oral cancer patients, frequent teeth brushing may help to reduce the risk of bacterial infection, which caused a DNA mutation which in turn led to the development of oral squamous cancer.
Professor Steve Rosen of the Duke-NUS’ CSCB programme, corresponding author of one study said, “There are bacteria that sometimes live in the human body, making a toxin that contributes to cancer formation. In addition to understanding what causes cancer, our results also indicate that some cancers that are caused by colibactin might be preventable.”
Moving forward, the research team is planning to investigate the link between colibactin and different types of cancer using a larger dataset. The on-going research at Duke-NUS’ CSCB programme continues to explore and discover cancer-inducing mutations, which will deepen the current understanding about the causal factors of cancer. With the new knowledge, improved and new preventive procedures can then be better implemented to lower the risk of developing cancer for all.