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Bacteria found in bowel tumours but link is unclear

Bowel cancer may be caused by a bacterial infection, The Independent has reported.

The story comes from a laboratory study that found that a bacterium called Fusobacterium nucleatum was present in much higher levels in colorectal cancer tissue than in healthy bowel tissue. The bacteria are normally found in the mouth rather than the bowel and are associated with dental infections.

While this study has found that a particular bacterium is present at high levels in bowel cancer tissue, it does not necessarily show that bowel cancer is caused by infection or that antibiotics could protect against it. For example, it might be the case that the bacteria are more able to infect cancerous tissue than healthy tissue, and may have only been introduced into a tumour once it had become established. That said, the finding is worthy of further exploration as bowel cancer is a major cause of cancer deaths and the causes are not fully understood.

Where did the story come from?

This Canadian study was carried out by researchers from the Michael Smith Genome Sciences Centre, Simon Fraser University, University of Guelph, and the Deeley Research Centre. It was funded by the Canadian Institutes of Health Research, Genome British Columbia and the Crohn’s and Colitis Foundation of Canada.

The study was published in the peer-reviewed journal Genome Research.

Alongside this study, the same journal also published another study that analysed the genetic material in samples from normal colon tissue and colonic cancers. This study also found an association between the presence of this pathogen and cancer but the authors are cautious and say that the precise role of the bacteria requires more investigation.

Both The Independent and the Daily Mail featured headlines that suggested antibiotics could protect against bowel cancer. This is misleading as the study did not show that the disease is caused by infection, nor did it investigate any potential treatments of bowel cancer.

However, within the body of their articles both newspapers correctly reported that the scientists do not know if the pathogen can actually trigger or cause bowel cancer.

What kind of research was this?

The researchers point out that colorectal cancer is the fourth leading cause of cancer deaths worldwide and that while the root cause is unclear, inflammation is a well-recognised risk factor. They note that stomach cancer is linked to inflammation caused by a bacterium called Helicobacter pylori and therefore planned to explore whether inflammatory organisms are associated with other gastrointestinal cancers.

In this cross-sectional laboratory study the researchers used genetic sequencing to compare the presence of microorganisms in tissue taken from bowel tumours and healthy bowel tissue.

What did the research involve?

The researchers isolated a type of genetic material called RNA from sets of stored cancerous and healthy bowel tissue originally taken from 11 patients with colorectal carcinoma. RNA is a type of genetic material similar to DNA that is found in both human cells and bacteria.

This isolated RNA was then analysed using genetic sequencing. This compared the microbial genetic code found in the healthy tissue and cancerous tissue and therefore indicated the type and volume of bacteria present in each type of tissue. If there were higher levels of a particular bacterium’s RNA in cancerous tissue than in healthy tissue from the same person, it might suggest that bacteria played some role in the development of cancer.

However, it should be noted that any association would not necessarily mean that bacteria causes cancer, as it may be the case that existing cancers are more susceptible to bacterial infections.

This initial testing had found an ‘overabundance’ of a particular bacterium called Fusobacterium nucleatum in the samples of cancer tissue. To further test this association the researchers performed more tests on 99 additional pairs of matched samples, also taken from patients with the disease, but using a test they had developed themselves to target specific genes they were interested in.

The researchers also looked at any association between the presence of Fusobacterium nucleatum and clinical characteristics such as tumour stage, history of treatment and survival, and the presence of secondary cancers.

What were the basic results?

In the first part of their study, researchers found that the presence of the pathogen Fusobacterium nucleatum was ‘markedly over-represented’ in tumour tissue compared to control specimens, with 9 out of 11 patients showing at least twice the levels of the bacteria in cancerous tissue as healthy tissue.

Further tests performed on matched tissue taken from 99 patients verified their results, with the average levels of Fusobacterium nucleatum being 415 times greater in tumour samples than in the matched normal samples.

They also found that patients with high levels of Fusobacterium nucleatum in their tumour tissue compared to matched healthy tissue were significantly more likely to have regional lymph node metastases (a type of secondary cancer).

How did the researchers interpret the results?

The researchers say their findings were unexpected, since Fusobacterium nucleatum is generally regarded as an oral pathogen, found in dental plaque and associated with periodontitis (gum disease).

They point out there is increasing evidence that this infection is common in colorectal carcinoma, although it is not clear if the pathogen plays any role in the development of the disease. They say its presence, ‘may simply represent an opportunistic infection of the ‘immune-compromised site”, in other words, the bacteria is present in greater amounts because it can infect cancerous tissue more easily.

The researchers add that the possibility the bacterium plays a role in the tumour development, possibly through inflammatory mechanisms, deserves further scrutiny. They say that future use of the bacterium as a means for estimating people’s risk of bowel cancer is currently speculative.

Conclusion

This study reflects a growing focus among researchers on possible associations between inflammation and the development of gastrointestinal diseases including cancer. It has been made possible by the development of genetic analysis methods in the last decade that allow researchers to analyse the relationship between microorganisms and cancer.

However, as the researchers note, it cannot show whether Fusobacterium nucleatum plays a causative role in the development of bowel cancer.

Furthermore, the tissue examined was taken from patients with existing bowel cancer, so the study cannot tell us at what stage the bacteria were first prevalent in the bowel: before, during or after cancer had developed.

To further explore the possible role of infection in the development of bowel cancer, researchers would need to screen healthy patients for the presence of bacteria and look at health outcomes in the period that followed, including the development of bowel cancer.

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