Obesity may be behind big rise in cancer of the gullet

A genetic mutation triggered by the obesity epidemic could lie behind the dramatic increase in a type of cancer which is affecting the UK more than any other nation.

Cancer of the oesophagus – or gullet – has been rising in all western countries as a result of a change in the nature of the disease. In the UK, the rate has risen by 50 per cent over the past 25 years, with around 8,500 new cases a year.

The cancer affects the foodpipe which extends around 26cm from the mouth to the stomach. It has one of the poorest survival rates of any cancer, with more than eight out of 10 patients dying within five years.

But whereas 40 years ago most cases were of squamous cell cancer which starts in the upper part of the oesophagus and is linked with smoking and drinking, today most cases are of adenocarcinoma, starting at the base of the oesophagus where the gullet meets the stomach.

Cases of adenocarcinoma have risen ten-fold over the past 40 years in the UK and it is now five times more common than squamous cell cancer, rates of which have remained stable. Among white men, the UK incidence of adenocarcinoma of the oesophagus is the highest in the world. Now a team led by scientists from the Dana Farber Cancer Institute in the US has found adenocarcinoma is linked with heartburn. A series of genetic mutations in tissue samples taken from patients with this type of cancer suggest it is caused by acid reflux.

Gad Getz, of the Massachusetts General Hospital and a lead author of the study published in Nature Genetics, said: "We discovered a pattern of DNA changes that had not been seen before in any other cancer type."

His colleague, Adam Bass of Dana Farber and the Broad Institute, added: "Gastric reflux can produce this type of damage, suggesting that reflux may underlie this pattern of mutations."

The oesophagus has a sphincter at its base to prevent the acid in the stomach gurgling back into it, damaging the lining and causing heartburn. In some men the sphincter ceases to work properly, a problem aggravated by obesity, allowing the lining to be eaten away which in turn may lead to cancer.

Men are almost three times more likely to develop adenocarcinoma than women partly because they have more severe reflux and because they are more likely to have excess weight around their waist rather than their hips – the apple vs pear shape – which increases the rate of reflux. Overall rates of oesophageal cancer – squamous cell and adenocarcinoma combined – are still higher among French men than British men. In Brittany it has been blamed on the "Calvados effect", the apple brandy made in that region.

The US scientists who sequenced sections of DNA in tissue samples taken from 149 patients with adenocarcinoma found 26 genes that were frequently mutated, indicating the cause was acid damage.

Dr Bass said: "Identifying the mutated genes within these tumours will help us understand the underlying biology. It also presents us with a slate of known genetic abnormalities that can some day be used to diagnose the disease at an early stage, classify tumours by the particular mutations, and ultimately develop treatment geared to precisely those mutations."

8,500 New cases of cancer of the oesophagus every year