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18 octobre 2011 2 18 /10 /octobre /2011 13:06

« Une bactérie serait impliquée dans le cancer du côlon »

 

« selon les travaux publiés simultanément par deux équipes nord-américaines dans la revue Genome Research, une bactérie habituellement peu répandue dans le tube digestif terminal, fusobacterium, est curieusement présente en abondance dans certains cancers du côlon ».

« l’équipe de Matthew Meyerson, à Harvard (États-Unis), l’a par exemple constaté en analysant l’intégralité du génome présent dans des carcinomes colorectaux ». 

L’un des coauteurs, le Dr Aleksandar Kostic (Harvard), écrit que ces « résultats démontrent une association entre fusobacterium et les cancers du côlon. Cela soulève la possibilité que fusobacterium puisse jouer un rôle moteur dans la cancérogénèse ».

Le chercheur précise toutefois qu’« il est possible que fusobacterium s’accumule là après que la tumeur se soit formée ».

« l’autre équipe de chercheurs, canadiens cette fois, a identifié la même bactérie, dans des échantillons congelés de tumeurs du côlon ».

Le Pr Jean-Philippe Merlio, chef du service de biologie des tumeurs au CHU de Bordeaux, réagit à ces publications : 

« Pour dire qu’un cancer est lié à une bactérie, il faut non seulement une association mais aussi une preuve de la responsabilité de l’agent infectieux et avoir vérifié la possibilité de l’inhiber ».

Le Dr Kostic remarque pour sa part que « pour démontrer le rôle causal de fusobacterium dans la cancérogénèse du cancer, s’il y en a un, on devra introduire la bactérie dans des souris et constater le développement de cancers du côlon. Il faudra ensuite prélever ces bactéries sur ces souris, les introduire dans d’autres et provoquer ainsi de nouveaux cancers du côlon ».

Le Dr François Ghiringhelli, cancérologue digestif et directeur de recherche d’une unité Inserm sur la chimiothérapie et la réponse immunitaire à Dijon, « n’écarte pas la possibilité que l’écologie bactérienne du côlon puisse être un facteur déclenchant de cancer ».

Le spécialiste déclare que « suivant l’alimentation, on pourrait modifier la flore intestinale et favoriser la carcinogénèse. Ici, c’est une bactérie qui pourrait jouer un rôle dans l’initiation ou le développement des cancers du côlon. 

Si cela se confirme, s’ouvriraient alors des perspectives thérapeutiques en éliminant la bactérie ».

Le quotidien observe enfin que « les implications de cette découverte vont au-delà puisque, s’il s’avère que la bactérie favorise effectivement le développement des cancers, le Dr Ghiringhelli estime que cela obligera à mieux préciser l’influence de la chimiothérapie sur la flore intestinale ».

 

Two Cancer Studies Find Bacterial Clue in Colon

 

 

For years, Dr. Robert A. 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?

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Cancers of the liver, stomach and cervix have all been linked to microbes, he knew. 

And if there is one place in the body with a lot of microbes, it is the colon — microbial cells outnumber human cells there by a ratio of at least nine to one.

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 the colon seems to have a disturbing affinity for colon cancers.

The two research groups discovered the link by analyzing genetic material in tumor 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 tumors although it normally is 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 tumor 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 tumors. 

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, Dr. 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 tumors than in normal colon cells.

“That, to me, was a real eye-opener,” Dr. Meyerson said. He expected lots of different bacteria in the tumor tissue, he said. “It turned out not to be that way.”

The two studies are published online Tuesday in 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 colon cancer cells had an average of 79 times as many Fusobacteria as normal cells.

The investigators then looked for the bacteria in 88 more tumors and corresponding adjacent noncancerous colon cells, using probes for Fusobacteria genes. 

With that more sensitive method, they found an average of 415 times as many Fusobacteria in the tumor cells as in the normal cells.

Dr. Meyerson and his colleagues did similar experiments but looked at DNA, the gene sequences, instead of RNA. 

They began with nine patients, finding Fusobacteria 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 the bacteria in the cancer cells.

“I don’t know what to make of it,” Dr. Meyerson said. “The bacteria are hanging around the tumors, 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. 

Dr. 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 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

Fusobacteria were known before this, of course, but were thought of as microbes that mostly live in the mouth — they are often in plaque and are associated with periodontal disease. 

But there are also recent reports associating them with ulcerative colitis and Crohn’s disease

Both of these diseases, especially ulcerative colitis, increase the risk of colon cancer.

But if the bacteria are linked to colon cancer, the question is how? 

One possibility, researchers say, is inflammation. Fusobacteria elicit inflammation, and cancer is linked to inflammation.

That does not necessarily mean that Fusobacteria cause cancer, Dr. Relman noted. 

Tumors themselves can cause inflammation, and some bacteria are quick to take advantage and invade damaged tissues.

“When you create inflammatory conditions, you select for certain organisms,” Dr. Relman said. 

“It almost doesn’t matter how you create the inflammation. 

There are organisms that are professionally adapted to inflammatory conditions.” 

In other words, he said, bacteria that are found among inflammatory cells might “simply be along for the ride.”

What remains is an intriguing finding, and a lot more work to figure out what is going on. 

Dr. Holt will be looking at polyps, tiny lumps on the colon wall. 

Colon cancers develop from polyps, though most polyps are harmless.

“The idea is that if we see infections in the early-stage lesions, maybe that is one of the factors that allows them to progress,” Dr. Holt said. 

“It does not provide a mechanism or prove anything, but it is consistent.”

Dr. Meyerson will be looking at animal models of colon cancer, asking if the bacteria can speed the development of cancer or even cause it.

But both investigators remain wary. 

“With an infectious agent in this type of research,” Dr. Holt said, 

“you never know, at least in the early stages of research, whether what you found is significant or if it is a red herring.”

Dr. Meyerson agreed. 

“It is hard to know yet how important it is,” he said. 

“It could be really important but, obviously, it also has the potential to go nowhere.”

 

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