Could bacteria be responsible for colon cancer? In papers published in the journal Genome Research, two research teams, working independently, describe a group of bacteria that are linked to higher rates of the disease.
Called Fusobacterium, this type of bacterium is very rarely found among the usual gut bugs, but it appears to flourish in colon cancer cells. “It was a huge surprise to me, because I didn’t expect to find any one class of bacteria [linked to colon cancer],” says Matthew Meyerson, a pathologist at the Dana Farber Cancer Institute and senior author of one of the papers.
The two research groups used sophisticated ways of sequencing genes to identify the bugs found in the tumor tissues. In the past, scientists would take biopsies and then try to grow bacteria or viruses in the lab to see what they were, but that was a hit-or-miss endeavor, since different microbes require different conditions in order to flourish. In the new studies, researchers used genetic probes, which can distinguish human from non-human material, to separate out then identify the microbes.
Meyerson’s group looked for DNA, starting with tumor tissue and healthy colon samples from nine patients. They found Fusobacteria DNA mostly in the cancer tissue. The group then confirmed those results in 95 other colon cancer patients, again finding Fusobacteria in tumors.
The other research group, led by senior author Robert Holt, a senior scientist at the British Columbia Cancer Agency Genome Sciences Center, focused on RNA instead of DNA. The benefit of the RNA approach, says Holt, is that compared to the bacterial genome, the human genome is huge — 3 billion base pairs, compared with the average bacterium’s 1 to 2 million base pairs — but only a small fraction, or 1% of the human genome is made into RNA, which is the active section of DNA that are made into products like proteins. Analyzing RNA means there is less human material to sequence and eliminate.
Holt’s team looked at colon cancer biopsies and normal tissues of 11 patients and found that Fusobacteria were more likely to be in cancer tissue than in normal cells. In some samples, they found hundreds of times more Fusobacteria in cancer cells than in healthy ones.
It’s the first time that Fusobacterium has been linked to cancer, though earlier studies have found that the microbes are associated with a higher risk of developing ulcerative colitis, a condition in which inflammation destroys the cells that line the colon and is also a risk factor for colon cancer. The bugs are otherwise mostly found in the mouth and are linked to periodontal disease.
The researchers further found that other types of bacteria that typically live in the gut are depleted in colon cancer tissues. Whether the Fusobacteria are crowding out these more common bugs, or whether they tend to die off in the presence of malignant cells isn’t known.
It’s also unclear whether or how Fusobacteria might be contributing to cancer. They may promote inflammation, which can lead normal cells to start dividing to become malignant. Or, it may simply be that the tumor environment is more hospitable to Fusobacterial growth, in which case the bugs would be a consequence, not the cause, of the cancer. “We need to try to get a better idea of which came first, the infection or the tumor,” says Holt. “These results now set things up for the justification studies that try to explore causality.”
The results are only the latest that expose the varied roles that pathogens like bacteria and viruses can play in conditions other than infectious diseases. Recent studies have linked certain forms of gut bacteria to a higher risk of obesity, for example. H. pylori, a bacteria that resides in the stomach, has been associated with gastric cancer and a form of lymphoma. The human papillomavirus, or HPV, is behind many cases of cervical cancer.
Research in this field, says Holt, is “highly underexplored. Compared to the time and effort and research focus on other cancer mechanisms, this one seems underrepresented but will probably provide a lot of interesting results.” And eventually, if the correlation holds up with other cancers, yield new treatments as well.
SPECIAL REPORT: Fighting Cancer