The link between cancer and infections

Can you ‘catch’ cancer? Strictly speaking no, but you can pick up an infection that increases the chances of developing certain types of the disease.

Certain infections are leading causes of cancer globally, causing up to one in five cancer deaths in the developing world. Better sanitation, antibiotics and vaccinations have helped to cut the numbers of people developing cancers linked to infections. But slashing infection rates further would have a major impact on cancer around the world.

What are these cancer-causing germs? And how do they work?

In the first of our Cancer and Infections series, we look at why certain infections can cause cancer. We’ll step back in time to see how researchers changed the scientific landscape by understanding these relationships, and show how research into viruses led to the fundamental discovery that the genes in our own cells have the potential to cause cancer.

This was the very dawn of cancer genetics, an area of science that has completely changed the way we tackle cancer. And, as we’ll see, the starring role was played by chickens.

Can germs give you cancer?

Broadly speaking, cancer is a disease of our genes – the biological instructions encoded within the DNA inside each one of the cells in our bodies.

Over the course of our lives we accumulate mistakes in our DNA – mostly through damage generated by the natural processes of life within our cells, but also from external sources of damage (carcinogens) such as tobacco smoke, UV radiation from the sun, and a lot more besides. And if enough genes get damaged, cells no longer understand their instructions and can become cancerous.

On top of this, certain types of infections can also lead to cancer developing. This is because these infections can also cause damage to our DNA and lead to changes within our cells.

But let’s be clear: don’t worry next time someone sneezes over you during your train journey because you can’t “catch cancer” from another person, nor does getting ill generally put you at any higher risk – only a few infections have links to cancer (and the common cold is not one).

And even having an infection that increases the risk does not mean that you will definitely develop cancer – in fact it’s very unlikely you will.

The obstacles scientists face

Pinpointing the links between infections and cancer poses a huge challenge for researchers.

To start with, we are continually chock full of germs – for example there are at least ten times the number of bacteria in the human body than human cells.

Trying to unravel the effect a single infection has on the risk of cancer among the millions of germs we encounter throughout our lives has been complicated, because scientists can’t study them independently of one another.

And it’s not just the sheer number of infections we encounter that’s an issue; timing also muddies the waters. Cancer is a multi-stage process that can take decades to develop, which could mean any infection detectable at the time of cancer diagnosis is an innocent bystander and the real culprit has long vanished without trace.

To add to this, there’s the baffling question of why cancer-linked infections only cause cancer in the minority of cases. In most instances other factors, like genetics and lifestyle, play an important role too.

Putting all these factors together has meant that it’s been very difficult for scientists to prove direct links between infections and cancer.

Finding a link has usually relied on large studies involving tens of thousands of people over long periods of time – recording and analysing vast amounts of information.

So what do we know?

Shiver me timbers, it’s a virus!

Viruses are the pirates of the natural world.

They are the barest bones of an existence – essentially just floating bits of genetic information in a protein overcoat. They don’t even have the machinery needed to reproduce themselves – the very definition of life.

But here’s the clever part: they commandeer other cells to do it for them. When you pick up an infection, the virus holds your cells hostage, hijacking your molecular machinery to make more copies of itself so it can spread.

And they manage this by smuggling their genes aboard our cells.

Many viruses make us feel unwell, but don’t have any link to cancer. But a small group of viruses, called oncoviruses, can lead to cancer for a couple of reasons. Some of these oncoviruses carry genes that mimic normal growth signals for our cells, instructing them to divide when they shouldn’t.

And sometimes the oncovirus thrusts its genes into an important bit of our DNA, which can play havoc with our own genes and make normally well-behaved cells go haywire.

The chicken came first

The first oncovirus was discovered in 1908 by two Danish scientists, Ellerman and Bang. They showed that something in the blood spread leukaemia between chickens, which could only have been a virus as it was so small.

But back in those days leukaemia wasn’t considered to be a cancer, and chicken maladies weren’t thought to be relevant to humans. So, unfortunately for the duo, their research efforts went largely unrecognised.

The scientist credited with the discovery of oncoviruses was an American called Peyton Rous, again working with chickens.

In a similar experiment just two years later, he showed that a type of soft tissue tumour called a sarcoma could be passed on by injecting a healthy chicken with the filtered blood from a hen with a tumour, meaning something so small it must have been a virus was causing the cancer. He was later awarded the Nobel Prize for this important finding.

The first proof that cancer could be caused by a virus in mammals was Richard Shope’s work in the 1930s, showing that a virus could transmit a type of skin cancer amongst cottontail rabbits.

And one of the most famous discoveries came just a few years later in 1936, when John Joseph Bittner proved that the mouse equivalent of breast tumours could be passed from a female mouse to her daughters via mouse mammary tumour virus (MMTV) in her milk.

Finally, in 1964, the first human oncovirus was discovered: the Epstein-Barr virus, or EBV for short, found by Cancer Research UK funded scientists Anthony Epstein and Yvonne Barr.

Revelations that other viruses were linked to human cancers followed, including some types of hepatitis, Human T-lymphotrophic Virus 1, human papillomaviruses, Kaposi’s sarcoma-associated herpesvirus, and Merkel cell polyomavirus.

A breakthrough discovery: from viruses to cancer genetics

Scientists studying the famous Rous chicken sarcoma virus in the 70s started tinkering around with its genetic information to pinpoint what was actually causing the cancer in hens. They discovered that a single viral gene was responsible, and named it src (pronounced sarc, short for sarcoma).

The “eureka” moment came in 1976, when Michael Bishop and Harold Varmus published their remarkable discovery that a wide range of animals carried the src gene within their own DNA.

Rather than src being an original viral gene, the virus had copied it from a human or animal during its evolution. This game-changing discovery later won them the Nobel Prize too.

The big question, of course, is why would one of our own genes cause cancer?

The answer is normally it won’t. Src is essential for us to develop and function normally, but if it becomes faulty or a cell has too much of it (for example due to a virus infecting our cells with additional overactive copies) it can lead to cancer.

This was the first time a human gene had been implicated in driving cancer development.

The study of a chicken virus thus kicked off an entirely new field of cancer genetics, and more cancer-causing genes – known as oncogenes – were soon uncovered.

What about bacteria and parasites?

It’s not just viral genes getting into our cells that can lead to cancer. A few bacteria and parasites have been associated with different types of cancer too.

There’s convincing evidence – which our scientists helped to provide – that a stomach bug called Helicobacter pylori increases the risk of stomach cancer and mucosa-associated lymphoid tissue (MALT) lymphoma.

A type of parasite (called a Schistosome) has been linked to bladder cancer, and some liver flukes increase the risk of cancer too.

There are still many question marks over the role other bacterial and parasitic infections may play, and which biological mechanisms cause bacterial and parasitic infections to lead to cancer.

Certain molecules or toxins made by the bacteria or parasites can turn on genes in our cells that stop faulty cells committing suicide (a normal way our body rids itself of damaged cells) and activate genes linked to increased cell division – fundamental processes in cancer. But our own cells play a role in driving cancer too.

Our own worst enemy

Unwittingly, our immune system – our robust lines of defence to protect us against viral, bacterial and parasitic infections – also plays a role in cancer developing.

One of the front lines of attack is the release of a powerful cocktail of chemicals, which both kills the trespassers directly and sends out SOS signals to call more immune cells into the area. This is what causes inflammation – the reddening and swelling you see at an infection site.

But when this inflammation persists over long periods of time, some of the chemicals can also damage our own DNA, increasing the risk of cancer.

And as our cells are damaged and lost – either due to the germs themselves or the immune attack – the body increases the number of new cells it makes to replace them.

Every time a cell divides it has to copy its DNA and mistakes can happen. So a long-lasting infection and a constant demand for new cells increases the risk from cancer over time by raising the risk of chance mistakes during DNA replication.

The bigger picture

In Western Europe and the US, most cancers are one of the “big four” – lung, breast, prostate and bowel cancers – and are mainly attributable to old age and lifestyle choices.

So what exactly is the risk of getting cancer through an infection?

In the case of people living in the UK, the answer is thought to be not very great, generally speaking. According to the World Health Organisation (WHO), about six in every 100 cancer deaths in developed countries are linked to an infection.

But that’s still six in every 100 deaths that could possibly be avoided. And certain infections are strong risk factors for specific cancer types, for example nearly all women who develop cervical cancer are infected with human papilloma virus (HPV).

But in other parts of the world, cancers with strong links to infections are a much bigger problem. Shockingly, one in five cancer deaths in developing countries are caused by infection.

For example Asia has high rates of stomach and liver cancers (linked to Helicobacter pylori and hepatitis infections), and cervical cancer and non-Hodgkin lymphoma (associated with human papillomaviruses and Epstein-Barr virus infections) are common in Africa.

Looking at the huge disparity between the number of cancer deaths caused by infections in developed and developing countries, it’s clear that many lives could be saved by improving hygiene standards and living conditions and lowering infection rates.

We’ve come a long way in uncovering how some infections can cause cancer, but there’s still a lot to do.

Unravelling the complex relationships between infections and cancer might lead to new tests to identify people at higher risk and also develop preventative treatments like vaccines.

And understanding more about the key mechanisms linking infections with cancer might shed light on innovative new ways to treat the disease.

Throughout this series we’ll be delving into how infections can cause stomach cancer, cervical cancer, and certain types of lymphoma, and how this knowledge has made an impact in the fight against cancer.

Finally, we’ll end with a glance into the future, looking at emerging evidence on the associations between infections and cancer and ways scientists are subverting infections to help us to treat the disease.

Note

Reference for oncovirus discovery: Ellerman, C., and O. Bang. (1908). Centralbl. Bakteriol. 46:595–609

Image credits: Sneeze image from Wikimedia Commons, bacteria image from Flickr, chicken image from Flickr, Helicobacter pylori image from Flickr.