Link Between Fusobacterium and Colorectal Cancer

Zosia Chustecka

October 18, 2011

October 18, 2011 — Two separate research teams have found strikingly high concentrations of Fusobacterium in tumor samples collected from colorectal cancer patients. This anaerobic bacterium is invasive and proinflammatory, and has been previously associated with a number of disorders, including inflammatory bowel disease, periodontitis, pericarditis, and thrombophlebitis.

Both studies appear online today in Genome Research.

Senior author Matthew Meyerson, MD, PhD, and colleagues note in their study that the association with colorectal cancer they found begs the question of whether the bacterium is involved in tumorigenesis.

"At this point, we don't know what the connection between Fusobacterium and colon cancer might be," said Dr. Meyerson, who is from the Dana-Farber Cancer Institute, Harvard Medical School, and the Broad Institute, Boston, Massachusetts.

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

The other study reporting the same finding comes from British Columbia, Canada, and was led by Robert Holt, PhD, from the BC Cancer Agency in Vancouver. Those researchers say that they were prompted to look for microorganisms in colorectal cancer because of the link between Helicobacter pylori and gastric cancer.

DNA Analysis in Boston

In Boston, Dr. Meyerson and colleagues sequenced DNA from 9 samples of colorectal cancer and 9 matched normal controls. They then validated the finding in a larger cohort of 95 paired specimens of colon cancer and normal colonic DNA.

Genomic analysis revealed a "significant enrichment" of Fusobacterium in colorectal carcinoma, they report. This enrichment was confirmed by histologic analysis of tumor tissue, as was the identification of Fusobacterium DNA in colon tumor metastases, they explain.

The team notes that Fusobacterium has previously been associated with inflammatory bowel disease, which is 1 of 3 high-risk factors for colorectal cancer. Other research has also shown that the bacterium is proinflammatory and can adhere to and invade epithelial cells.

They speculate that it contributes to tumorigenesis, perhaps in a limited subset of patients, by an inflammatory-mediated mechanism.

However, they acknowledge that "it is possible that Fusobacteria accumulate in the tumor microenvironment in the late stages of tumorigenesis, and therefore do not have a significant role in tumor development."

"Our results do not prove a causal relationship," they emphasize. "The establishment or repudiation of such a relationship will require further studies."

RNA Analysis in British Columbia

In British Columbia, Dr. Holt and colleagues analyzed 11 matched pairs of colorectal carcinoma and adjacent normal tissue specimens, and validated the findings in an additional 88 colorectal carcinomas and matched normal specimens. They sequenced RNA rather than DNA to detect active transcribing microorganisms.

They found a highly significant overrepresentation of Fusobacteria, specifically Fusobacterium nucleatum, in the colorectal tumor samples. This finding was "largely unexpected, given that it is generally regarded as an oral pathogen," they add.

This research team speculates on the role that the bacterium play in tumorigenesis, and suggests that further studies look specifically at colorectal carcinoma arising in association with inflammatory bowel disease and for the bacterium in early-stage adenomatous polyp lesions, which are precursors of colorectal cancer.

If it turns out that the bacteria are involved in the early stages of tumor progression, this could offer a target for antimicrobial therapy and/or vaccination, the researchers explain.

However, they also make the point that the presence of Fusobacterium in colorectal cancer samples "may simply represent an opportunistic infection at an immunocompromised site."

Nevertheless, the possibility of a role in tumor etiology deserves further scrutiny, they conclude.

Genome Res. Published online October 18, 2011. Abstract, Abstract


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