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Do infections trigger colon cancer?
For years, Robert Holt, a genomics researcher at the British Columbia Cancer Agency, wrestled with a question about colon cancer: Might it be caused or pushed along, by a bacterial infection?
Cancers of the liver, stomach and cervix have all been linked to microbes, Dr. Holt knew. And if there is one place in the body with lots of microbes, it is the colon- microbial cells outnumber human cells there by a ratio of at least 9 to 1.
The new tools of genomic analysis offered an opportunity to look for a connection. What Dr. Holt and another group of researchers working independently have found is completely unexpected and puzzling. One particular species of bacterium never particularly prevalent in colon seems to have a disturbing affinity for colon cancers.
The two research groups discovered the link by analyzing genetic material in tumour samples. They then subtracted human genes from the mix. What remained were microbe genes.
An analysis of these microbial genes showed that a type of bacterium, Fusobacterium was abundant in the tumours although it was normally not among the more prominent species in the gut. Not only were the bacteria lurking around the cancer cells but Dr. Holt found in subsequent experiments that they actually were burrowing into tumour cells –“which is kind of creepy,” he said. An ability to invade cells, he said, is often what distinguishes a disease-causing microbe from one that is harmless.
Of course, that doesn’t prove that Fusobacteria are causing tumours. They might just find the cancer cells a good place to live.
As Dr. Holt and his colleagues investigated further, they found the bacteria were especially prevalent in patients whose cancer had spread beyond their colons.
The finding could have been an anomaly. But, with no knowledge of Dr. Holt’s results, Matthew Meyerson and his colleagues at the Dana-Farber Cancer Institute in Boston found the same thing. And while Dr. Holt’s patients were from Canada, Dr. Meyerson’s were from people in the United States, Vietnam and Barcelona, Spain. All had the bacteria in far greater abundance in their tumours than in normal colon cells.
“That, to me, was a real eye opener,” Dr. Meyerson said. He expected lots of different bacteria in the tumour tissue, he said. “It turned out not to be that way.”
The two studies were published this week by the journal Genome Research.
In their study, Dr. Holt and his colleagues began by looking at RNA, which reflects active genes, from 11 colon-cancer patients. The cancer cells had an average of 79 times as many Fusobacteria as normal cells.
The investigators then looked for the bacteria in 88 more tumours and corresponding adjacent non-cancerous colon cells, using probes for Fusobacteria genes. With that more sensitive method, they found an average of 415 times as many Fusobacteria in the tumour cells as in the normal cells.
Dr. Meyerson and his colleagues did similar experiments but looked at DNA sequences mostly in the cancer tissue. Then they looked at cells from an additional 95 patients, searching specifically for Fusobacteria gene sequences. Again, the researchers found bacteria in the cancer cells.
“I don’t know what to make of it,” Dr. Meyerson said. “The bacteria are hanging around the tumours, but I have no idea if they spur or cause cancer.”
But the findings are at the very least provocative, said microbiologists and experts in colon cancer. David Relman, a microbe expert at Stanford University, said he was especially struck by the fact that two independent labs, using samples from different parts of the world, found the same thing.
“I look at these and say, “Yes, there may be a real association,’” he said.
If Fusobacteria actually do predispose humans to colon cancer one day researchers may be able to devise a colon-cancer vaccine, much like the HPV vaccine that protects against cervical cancer.
New York Times News Service