Investigators from the Wistar Institute in Philadelphia, PA presented their work today at the 2014 American Association for Cancer Research Annual Meeting in San Diego, CA. Their research suggests that the gut bacteria responsible for gastric upset may also create an “incubating” environment that increases the risk of colon cancer, and promotes the growth of tumors.
According to Frank Rauscher III, the Senior Investigator, there are a number of unanswered questions about how colon cancer forms, and how it transforms into a malignant tumor. His research provides evidence that the gut bacteria under study can promote genetic changes that enable the progression of the cancer. Most cells in the human body have natural mechanisms for repairing damaged or broken DNA. Colon cancer occurs when healthy epithelial cells in the gut begin to accumulate mutations and form polyps; eventuating in malignancies. The gut bacteria studied in this project apparently produce proteins that impair the cells’ natural DNA repair processes, leading to increased risk of colon cancer. This research suggests that a possible avenue of reducing the risk of colon cancer might be to alter the bacterial flora of the gut, especially for people at higher risk.
At this time incidence of colon cancer is falling, especially among older Americans; likely because of increased screenings. Unfortunately, although incidence is on the decline, the disease will still kill approximately 50,000 people this year. Although scientists have a better understanding about the gene mutations that affect gut cells, their findings have not yet improved overall rates of survival.
The human gut is home to approximately 10 trillion bacteria, many of which are not well known. Some of these bacteria are ‘friendly,’ and provide assistance to their human host by helping with digestion and providing protection from other disease-causing microbes. Recent studies show that many gut bacteria – both friendly and otherwise – produce proteins that work to reduce inflammation, which is important for healing and for limiting infections. Dr. Rauscher and his researchers studied the effects of some anti-inflammatory proteins put out by a bacterium known as Enteropathogenic Escherichia coli (EPEC). The researchers injected the anti-inflammatory proteins into colon cells in culture. From these experiments they identified a bacterial protein (NLEE) which blocks a human gut protein (TAB2) resulting in the inhibition of many gut inflammatory responses. The team next looked at NLEE’s effect on other human gut proteins, and found that it blocks another human protein (ZRANB3) which functions in repair of human DNA; when this protein is blocked, mutations that might cause cancer are able to accumulate in the cells lining the gut. At the heart of the molecular mechanism of NLEE’s action is its ability to interfere with a structural domain on its target molecules called a “zinc finger.” At least three other DNA repair enzymes besides TAB2 and ZRANB3 contain the zinc finger domain, which suggests that NLEE can interfere with several natural mechanisms that are in place to prevent cancer.
All in all, the research would indicate that some bacteria living in the gut may have a more sinister role than simply causing gastric upset. By limiting the human host’s natural DNA repair mechanisms in intestinal cells, these gut bacteria may increase the risk of colon cancer and promote the development of tumors.
By Laura Prendergast
American Association for Cancer Research