World Cancer Day 2017: there are 2 types of oesophageal cancer, and they affect the world in different ways

In the final part of our World Cancer Day series, we take a look at how oesophageal cancer affects different regions across the world. Take a look at our interactive map below to see how the rates vary, and read on to find out what the differences in rates can tell us about the causes of the 2 main types of oesophageal cancer.

In the UK, oesophageal cancer rates have gone up by more than 40% since the 1970s. Lifestyle factors – such as smoking, being overweight or obese, and drinking alcohol – cause almost 9 out of 10 oesophageal cancers in the UK.

But is the same true in other parts of the world? Oesophageal cancer rates are highest in Southern Africa and Eastern Asia, where alcohol consumption is lower and obesity is less common. So what’s driving up rates of oesophageal cancer in these regions?

There are 2 main types of oesophageal cancer and, intriguingly, they are linked to different causes, which is reflected in the patterns of diagnoses.

In this post we dig deeper into these trends, and explore some of the possible reasons behind them with 2 experts working in the field.

Getting to the root of the situation

Oesophageal cancer is the 8th most common cancer worldwide. The disease affects the long stretchy tube that carries food and drink to the stomach, and can be split into 2 main types.

The first, called squamous cell carcinoma, occurs in the upper portion of the oesophagus. And the second, called adenocarcinoma, develops in the lower region as well as where the oesophagus meets the stomach.

They are strikingly different at the genetic level, so much so that a recent study called for their classification to be reconsidered, identifying them as separate diseases.

And the differences between these cancers don’t end there.

Just as they affect different parts of the oesophagus, these cancers also differ in the areas of the world that they affect. That’s largely due to the fact that they have different possible underlying causes, and as behaviours and lifestyles shift over time in different populations, so too do the rates of these cancers.

Let’s look at the figures more closely.

Hotspots for hot teas

If you look at the map above, the countries with the highest levels of oesophageal cancer are in Asia and Africa. Here, the vast majority of cases are squamous cell carcinoma, which remains principally a disease of less developed regions.

In part, this can be explained by the major risk factors for this type of cancer: smoking tobacco, drinking alcohol and hot beverages, and poor nutrition.

Oesophageal cancer is one of a series of cancers from the lips to the lungs that are linked with smoking

– Dr Phil Jones, Cancer Research UK

“Smoking rates are now high in the parts developing world,” says Dr Phil Jones, a Cancer Research UK expert on oesophageal cancer from the University of Cambridge.

“And oesophageal cancer is one of a series of cancers from the lips to the lungs that are linked with smoking.”

Drinking very hot beverages, defined as above 65C – much hotter than is common in Europe and the US – is also a cultural tradition of certain countries that raises the risk of this cancer, and we see that reflected in rates of the disease.

“In Iran and a few other countries, people drink tea at very hot temperatures and that damages the lining of the oesophagus,” explains Dr Marnix Jansen, a Cancer Research UK expert on oesophageal cancer from University College London. This could cause harmful inflammation leading to cancer or increase the risk of damage to cells from cancer-causing substances that make their way into the oesophagus.

A case of whodunnit?

Although these major risk factors for oesophageal squamous cell carcinoma can explain a lot of the global differences, they don’t tell the whole story.

“But mysteriously, in terms of this global health problem, there are large areas of Africa where the cause of oesophageal cancer isn’t obvious,” says Jones.

“Whatever it is, it doesn’t appear to be one of the usual suspects – smoking or alcohol.”

Different cancer-causing substances, or carcinogens, leave unique ‘fingerprints’ of damage on cells’ DNA, offering clues as to where the damage originated. And when scientists looked at these ‘fingerprints’ in oesophageal squamous cell carcinoma patients in Malawi – which has the highest rates for this cancer in the world – they didn’t match up with those left by cigarette smoke.

“This tricky story is hard to resolve, but one idea is that cases could be related to a fermented milk that’s drunk in some African countries,” says Jones.

Mysteriously… there are large areas of Africa where the cause of oesophageal cancer isn’t obvious

– Dr Phil Jones, Cancer Research UK

“This contains lots of carcinogens called aldehydes, which are also found in alcohol,” he adds. On top of that, says Jansen, charcoal is mixed into the milk to get rid of bacteria, which can also be a source of carcinogens.

Another area where cases don’t quite marry up with exposure to risk factors is the so-called ‘Asian oesophageal cancer belt,’ which stretches across the Central Asian republics, Mongolia and north-western China.

Here, it’s thought that inherited genetic changes might be playing a role. In particular, a variation of a gene called ALDH, which is common in some Asian populations.

People who have this variation can’t efficiently break down one of alcohol’s toxic by-products: acetaldehyde. Acetaldehyde is a carcinogen and, according to Jones, the higher levels of the toxin in people carrying the gene variant has a big impact on oesophageal cancer rates.

“That’s the strongest single gene change that a person can be born with which can predispose to this type of cancer, if they drink alcohol,” he says.

Scientists are now looking at possible ways to identify people with this gene variant in order to develop strategies that could reduce their risk of developing oesophageal cancer, for example by offering lifestyle advice or screening.

But it’s not just Asia and Africa that are seeing oesophageal cancer rates in flux.

Under pressure

In the West, particularly the UK and US, we’re seeing oesophageal squamous cell carcinoma rates drop, largely due to decreasing smoking and drinking rates. Yet adenocarcinoma rates are soaring.

Over the last few decades, the US has seen a 400% increase in the rates of this type of cancer, resulting in death rates climbing from 2 to 15 per 100,000 over the same time period. And one possible explanation is rising levels of obesity.

Obesity is a major risk factor for oesophageal adenocarcinoma, but not squamous cell carcinoma, and is a growing public health issue in the developing world. It’s thought that excess fat around the waist puts pressure on the abdomen, causing stomach acid to make its way up the oesophagus and damage its lining. This process is known as acid reflux.

This makes sense given that another condition linked to persistent acid reflux, called Barrett’s oesophagus, increases the risk of oesophageal adenocarcinoma. In fact between 7 and 13% of people in the UK with this condition go on to develop oesophageal cancer.

So what’s next?

While studying these trends is interesting, it’s what researchers can do with this information that’s important.

As Jones explains, if we can find an avoidable risk factor that could form the basis of some kind of prevention strategy, then public health measures could help lower the risk of disease.

“In developing nations where the cause of oesophageal cancer is unclear, the hope is that we can find a risk factor in the diet or environment that is easy to get rid of at a low cost,” he says.

“Then maybe this will have an impact on disease rates.”

And as Jansen points out, rising rates of the disease mean that finding new ways to diagnose the disease earlier are also important.

The harder you look, the more [cancer] cases you will find

– Dr Marnix Jansen, Cancer Research UK

“Cancer Research UK scientists are working on early detection aids, such as the Cytosponge test,” he adds. This is a simple test that could be used in patients with Barrett’s oesophagus to pick up early changes in cells. It’s also one that could be applied worldwide; we’ve already teamed up with the Chinese Academy of Medical Sciences to test Cytosponge in areas of China that have high levels of oesophageal cancer.

Early diagnosis is important because cancer that’s picked up at earlier stages is more likely to be treated successfully. But Jansen highlights that such tests need to be accurate enough to avoid picking up cancers that wouldn’t have gone on to cause the person any harm – so-called ‘overdiagnosis’.

“The harder you look, the more cases you will find,” he says. “So now the big question is: what do we do once we identify these patients with early cancer? Not all of them will go on to develop aggressive disease that requires intense treatment.

“We need to develop better tools to distinguish these patients from those who need monitoring to prevent potentially harmful overtreatment. That’s the future of early detection.”

And just like improving detection and diagnosis, there is much to be done to help prevent more cases of oesophageal cancer as well as finding better, gentler treatments – all things our dedicated researchers are working hard to achieve.

Justine