A bug’s life: H. pylori and stomach cancer

The second post in our Cancer and Infections series looks at a stomach bug called Helicobacter pylori, or H. pylori for short, and how it’s linked with cancer.

Back in the 1800s, surgeons treating patients with stomach cancer first suggested that ulcers were a pre-cancerous condition, and that years of irritation to the stomach led to the cancer developing in some people. But no one really understood the causes of this persistent irritation.

Prior to the 1980s, dogma was that stomach ulcers (also called peptic ulcers) and inflammation of lining of the stomach (gastritis) were down to stress or diet, with key culprits being alcohol, coffee, and acidic and spicy foods.

But a pair of clever Australian scientists, Robin Warren and Barry J. Marshall, were about to turn this thinking on its head. In the early 80s they noticed that most people with stomach ulcers have the same type of bacteria in their stomachs, later named H. pylori.

At first their claims were widely dismissed, on the grounds that nothing could possibly survive in the hostile acidity of the stomach. In a heroic effort to prove his point, Marshall deliberately drank a broth containing H. pylori. True to his word, he rapidly developed gastritis. Thankfully, H. pylori infection can be treated with antibiotics, so he was able to rectify his self-induced illness.

Finally people came round to Warren and Marshall’s idea, and other scientists soon found more evidence that added weight to their conclusion. It’s now accepted that ulcers and chronic gastritis are caused in most cases by H. pylori bacteria in the stomach.

From gastritis to stomach cancer

Meanwhile, scientists elsewhere in the world had been studying people with stomach cancer to try and tease out the causes of the disease.

In the 70s, Columbian scientist Pelayo Correa studied large groups of people in South America. He noticed that stomach cancer developed in a multi-step process which began with years of chronic stomach inflammation.

Soon researchers were putting two and two together: if H. pylori infection was the main cause of stomach ulcers and chronic inflammation, and inflammation a pre-cursor to stomach cancer, then it stood to reason that infection with the bugs could be a leading cause of cancer.

It was a neat idea – but someone had to prove it.

Our researchers joined the dots

The first indications of a link between H. pylori and stomach cancer came from scientists who spotted that rates of the disease were highest where infection was rife. But these studies were small and were not enough to prove that the bacteria were the true culprit.

In 1990, we funded a large observational study of people – called an epidemiological study – run by Professor David Forman. To prove a link between a risk factor and cancer you usually need to collect information from large numbers of people, so Forman looked to the East and one of the biggest countries in the world where H. pylori infection was commonplace – China.

Forman tested blood samples for signs of H. pylori infection from men of all different ages from 46 regions across rural China, ranging from areas of high and low rates of stomach cancer. He then matched the blood samples to records of causes of death kept by the health registries.

When he compared how many men died from different types of cancer to whether they were infected with the stomach bacteria, the only cancer-related cause of death that was more common in the group of infected men was stomach cancer.

This was the first wide scale study confirming a link between H. pylori and stomach cancer. It was also the first time a bacterial infection had been shown to increase the risk of getting cancer.

A simple fix?

In developed countries the numbers of people diagnosed with stomach cancer have steadily fallen since the early 1900s. In the UK alone, the number of cases of stomach cancer has halved in the last 30 years.

There are several reasons for this, including a drop in the number of people infected with H. pylori. Improved sanitation, less overcrowded living conditions, and wide scale use of antibiotics have all played a role in reducing the number of people infected with H. pylori, and so lowered stomach cancer rates.

Other changes that have also contributed to this fall in stomach cancer rates are lifestyle related.

The introduction of refrigeration helped keep food fresh and germ-free for longer, and cut the use of salting to preserve food – high levels of salt in the diet are also a risk factor. Generally, an overall improvement in our diet has helped lower the number of people being diagnosed with this disease.

But stomach cancer is the second biggest cause of cancer-related deaths across the world. And infection with H. pylori is still a big health burden globally, especially in developing countries. It’s estimated that around three quarters (74 per cent) of all of middle aged adults in developing countries are infected, compared to just over half (58 per cent) in developed countries.

Because people with an H. pylori infection have a roughly six-fold greater risk of developing stomach cancer than uninfected people, experts suggest that the bacteria may be responsible for almost 600,000 cases of stomach cancer every year – that’s over five per cent of all cancers globally.

And a further 11,500 people diagnosed with a type of lymphoma in the stomach called mucosa-associated lymphoid tissue (MALT) are thought be a result of H pylori infection. There’s also some evidence that the bacteria may increase the risk of developing pancreatic cancer.

Given that H. pylori infection can be cured with a course of antibiotics, the solution seems simple at first glance.

A sting in the tail

But in an intriguing twist, studies have shown that H. pylori infection might have its advantages.

While there is no concrete evidence yet, there are some data to suggest that infection, especially in childhood, could help stop the development of some allergic disease like asthma. More surprisingly, there’s also evidence from large studies that the stomach bugs could be protective against oesophageal cancer – although why and to what extent is not clear yet.

Furthermore, despite the evidence that H. Pylori is a strong risk factor for stomach cancer, only a minority of infected people develop cancer.

There are theories to explain these conundrums. Different types of bacteria have different effects, the age and duration of infection may play a role, and simultaneous infections with other bacteria might contribute to cancer developing. Also, people’s genes may influence whether infection alters their risk of cancer.

We’ve come a long way in understanding the role that H. pylori plays in cancer – but there are still questions to answer. That’s why we continue to fund research in this area, looking for some of these answers.

For example, we’re funding a large study to find out whether treating middle-aged people to cure them of their H. pylori infection reduces their risk from stomach cancer to that of an uninfected person.

Research like this is important to identify what actions we should be taking to continue reducing the number of people losing their lives to stomach cancer.

Image credit: Helicobacter pylori image from Wikimedia Commons