Newly discovered virus linked to colorectal cancer

Colorectal cancer is one of the most common types of cancer in the Western world and a leading cause of cancer-related deaths. Age, diet and lifestyle are known risk factors. However, in most cases we still lack a precise understanding of what triggers the disease.

In recent years, researchers have increasingly turned their attention to the ecosystem of the gut – the vast community of bacteria, viruses and other microorganisms that live there.

Now, researchers from the University of Southern Denmark and Odense University Hospital have discovered a previously undescribed virus in a common gut bacterium. The virus appears more frequently in patients with colorectal cancer.

A familiar bacterium – but an unsolved puzzle

For several years, one particular bacterium has been associated with colorectal cancer: Bacteroides fragilis.

The difficulty is that this bacterium is also present in the vast majority of healthy individuals.

– It has been a paradox that we repeatedly find the same bacterium in connection with colorectal cancer, while at the same time it is a completely normal part of the gut in healthy people, says Flemming Damgaard, medical doctor and PhD at the Department of Clinical Microbiology at Odense University Hospital and the University of Southern Denmark.

The researchers therefore decided to examine whether differences might exist within the bacterium itself.

They did.

A virus hidden inside the bacterium

In patients who later developed colorectal cancer, the bacterium far more often carried a specific virus – a virus that lives inside bacteria, known as a bacteriophage.

– We have discovered a virus that has not previously been described and which appears to be closely linked to the bacteria we find in patients with colorectal cancer, says Flemming Damgaard.

According to the researchers, the virus represents new types that have not previously been identified.

– It is not just the bacterium itself that seems interesting. It is the bacterium in interaction with the virus it carries, he explains.

The study demonstrates a statistical association between the virus and colorectal cancer, but it cannot determine whether the virus plays a direct role in the development of the disease.

– We do not yet know whether the virus is a contributing cause, or whether it is simply a sign that something else in the gut has changed, says Flemming Damgaard.

The discovery began in Denmark

The research began with data from a large Danish population study involving around two million citizens.

The researchers identified patients who had experienced a serious bloodstream infection caused by Bacteroides fragilis. A smaller group of these patients were diagnosed with colorectal cancer within a few weeks.

The team analysed the bacterium’s genetic material in patients with and without cancer and identified a distinctive pattern: bacteria from cancer patients were more often infected with specific viruses.

The initial finding was based on a relatively small number of bacterial samples from Danish patients. However, it revealed a pattern that the researchers were later able to examine in larger international datasets.

– It was in our Danish material that we first detected a signal. That gave us a concrete hypothesis, which we were then able to investigate in larger datasets, says Flemming Damgaard.

Tested in nearly 900 people from several countries

To determine whether the pattern also applied outside Denmark, the researchers analysed stool samples from 877 individuals with and without colorectal cancer from Europe, the United States and Asia.

They found that patients with colorectal cancer were approximately twice as likely to have traces of these viruses in their gut.

– It was important for us to examine whether the association could be reproduced in completely independent data. And it could, says Flemming Damgaard.

The results point to a robust statistical association across several countries. However, they do not establish whether the virus causes the disease.

A new perspective on colorectal cancer

Up to 80 per cent of the risk of developing colorectal cancer is linked to environmental factors. The microorganisms in the gut are believed to be among the most important.

The gut contains thousands of bacterial species and even more genetic variations. This complexity has made it difficult to identify precisely what distinguishes healthy individuals from those who develop disease.

– The number and diversity of bacteria in the gut is enormous. Previously, it has been like looking for a needle in a haystack. Instead, we have investigated whether something inside the bacteria – namely viruses – might help explain the difference, says Flemming Damgaard.

If the virus alters the properties of the bacterium, it could potentially change the gut environment. This is one of the questions the researchers are now exploring.

– We do not yet know why the virus is present, but we are investigating whether it contributes to the development of colorectal cancer, he says.

A potential tool for future screening

Today, colorectal cancer is detected partly through stool tests that screen for hidden blood.

The researchers suggest that it may one day be possible to test stool samples for the viruses they have identified.

– In the short term, we can investigate whether the virus can be used to identify individuals at increased risk, says Flemming Damgaard.

In preliminary analyses, selected viral sequences were able to identify around 40 per cent of cancer cases, while most healthy individuals did not carry them.

The researchers emphasise that the findings are still at an early and experimental stage. Further studies are needed before the method could have implications for clinical practice.