Microbe an Unusual Suspect in Colon Cancer

Derek Cassels

June 21, 2012

June 21, 2012 — Using cutting-edge metagenomics techniques to explore the pathogens present in colorectal cancer, 2 research teams working independently have uncovered a totally unexpected suspect.

The microbe Fusobacterium nucleatum, which is associated with inflammatory and infectious diseases, including periodontal disease, appendicitis, pericarditis, and brain abscesses, might be implicated in colon cancer.

The 2 studies were published in Genome Research.

"We were looking for pathogens in 11 colon cancers. What we found was a complete surprise. F nucleatum was the microbe most differentially abundant between the cancer specimens and healthy tissue. It was remarkably high in many instances," Robert Holt, PhD, principal investigator of one of the studies, told Medscape Medical News.

Dr. Holt's team, from the British Columbia Cancer Agency in Vancouver, Canada, found that more than 95% of the pathogens in the tumors were bacterial.

The viruses include the usual suspects, such as hepatitis B and C; however, the abundance of F nucleatum was novel. The differential abundance of F nucleatum in bacteria ranged from 0.1-fold to 256-fold, with a mean 79-fold overabundance, the researchers report.

Taking it a step further by looking in a larger group of colon cancers, F nucleatum abundance was even higher — up to 415 times more abundant in cancer specimens than in healthy tissue.

Next Steps

Where does the research go from here?

If anything, this research "raises a whole bunch of questions — some straightforward, others difficult to answer," Dr. Holt said.

"What we are embarking on now is to isolate, by culture, additional tumor strains. We managed to isolate by culture 1 tumor strain entirely by chance, even though the samples had been frozen and we weren't expecting to get any at all."

Dr. Holt and colleagues are now trying to determine whether there is something unique about the F nucleatum microbe, which has been found in other infections and mucosal surfaces.

"We have to isolate more strains and sequence the genome of those bacteria and compare them," said Dr. Holt.

One strain, code named CC53 (colon cancer 53), is a possible marker for the development of the cancer.

As with Helicobacter pylori, which is associated with gastric cancer, it might be possible to eradicate F nucleatum before it has a chance to adhere to and inflame mucosal tissues, initiating cancerous changes.

Most Dominant Phylotype

In the second study, researchers from the Dana-Farber Cancer Institute in Boston and the Broad Institute Massachusetts Institute of Technology in Cambridge also examined the microbial composition of colorectal tumors. Their results were similar to those of Dr. Holt's team.

Using DNA analysis, the researchers, led by Matthew Meyerson, MD, PhD, found that "the relative abundance of Fusobacterium was highly enriched in the population of tumor vs normal samples."

They then looked for an association between these microbes and the survival or maintenance of cancer cells.

Dr. Meyerson and colleagues note that Fusobacterium "may be uniquely related to pathogenesis of subsets of colorectal cancer."

The researchers also found that F nucleatum was the most dominant phylotype inside cancer, but noted that some tumors contain more than one dominant species.

The presence of these microbes, they add, suggests that they "contribute to tumorigenesis, perhaps in a limited subset of patients, most conceivably by an inflammatory-mediated mechanism."

Early Marker?

However, it is possible that Fusobacteria accumulate in the later stages of tumor development and do not play any significant role in cancer development, the researchers note.

Both research teams caution that they have yet to prove a causal relation between these microbes and the development of colorectal cancers.

"At this point, we don't know what the connection between Fusobacterium and colon cancer might be," Dr. Meyerson, who is also professor of pathology at Harvard Medical School in Boston, said in a statement.

"It may be that the bacterium is essential for cancer growth or that the cancer simply provides a hospitable environment for the bacterium. Further research is needed to see what the link is," he added.

Dr. Holt said that there might be more of a near-term benefit if a variant strain can be used as a marker for the development of colon cancer.

"If we are able to read a signal, it certainly would be easier to screen than colonoscopy. This is important because the disease is so deadly and it is not usually detected until it is established in a later stage," he said.

The authors have disclosed no relevant financial relationships.

Genome Res. 2012;22:292-298, 299-306. Abstract, Abstract

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