New clues on oesophageal cancer

MRC News

Oesophageal cancer is one of the major cancers affecting black males in South Africa. However, the type of oesophageal cancer prevalent in less developed countries differs from the type prevalent in developed regions such as Europe and the USA. This makes the research work of the MRC's Oesophageal Cancer Research Group vital.

Scientists still speculate about the cause of oesophageal cancer - some people point to dietary causes, while others look at environmental and genetic factors. Prof. Iqbal Parker, Director of the Oesophageal Cancer Research Group, points to another fascinating piece of information.

"What I find very interesting is the high incidence of the disease in the so-called 'maize belt' of Africa - the eastern part of the continent where maize is a staple food. In contrast to this, the western side of Africa, where the same factors of poverty and malnutrition are present, has a very low incidence of oesophageal cancer," he explains.

Oesophageal cancer and genes

This could point to a genetic factor, so one of the Group's research avenues is to find a gene that could predispose you to oesophageal cancer. "We know the early African populations migrated from West to Central Africa, and then spread to the North and South. So it could well be that those moving southward had a certain genetic make-up … almost like a type of 'founder effect', similar to the Dutch bringing the genes for familial hypercholesterolemia to the Cape," Prof. Parker says.

Investigating this isn't as easy as it might sound. In contrast to familial hypercholesterolemia, where the scientists know which genes could be candidate genes for mutations, they don't have anything to go by with oesophageal cancer. So they look at so-called oncogenes and suppressor genes - these are genes which are involved in other types of cancer.

"But as far as I'm concerned, the answer lies in a combination of dietary, genetic and environmental factors. One group of genes that will couple these factors, are the 'detox' genes. If you are exposed to a harmful substance, these genes will detoxify the body. But sometimes the genes do not work as well as they should, so the toxins slowly accumulate in your body. What we are doing is to try and establish a 'genetic detoxification gene profile' of oesophageal cancer patients, to see whether there is a certain genetic profile that makes people susceptible to oesophageal cancer," he explains.

Papilloma virus

Prof. Parker's team recently found that more than 50% of their patients have integrated human papilloma virus in their tumour DNA.

There are two forms of human papilloma virus - a 'high risk' form responsible for causing cervical cancer, and a 'low risk' form that causes warts. In this case, the scientists have found the 'low risk' form to have been integrated into the tumour DNA.

"This could point to an infectious agent being responsible for the cancer and it opens up a whole new area of research. How did the viral DNA get into the tumour cells? What role does it play in oesophageal cancer? What is the mechanism by which they induce tumour formation? It opens a completely new can of worms," says Prof. Parker.

Their discovery could bring a new dimension to the early detection of the disease. "We hope that, if the papilloma virus indeed plays a role, we could use the 'brush biopsy technique', also developed by MRC researchers (see here). We could analyse the oesophageal cells trapped on the brush to see if they contain any viral DNA, and if they do we could monitor these patients very closely to pick up the disease at a very early stage," Prof. Parker explains.

Their discovery could also point the way to new drugs that could block the production of viral proteins in the oesophageal cells. "The papilloma virus can be grouped as an environmental factor - a carcinogen that comes from the outside. But I believe that a number of carcinogens may play a role - it's a multifactorial process, like any other cancer," he says.

"This points to the possibility of an infectious agent being responsible for a cancer. This could be a breakthrough in our understanding of the disease and will radically change current thinking on the aetiology of the disease. A paper about this work is in press. We now have to address the question of how the papilloma virus DNA gets into the oesophageal cells - and why it specifically targets these cells," Prof. Parker explains.

Different form of cancer

According to Prof. Parker, the type of oesophageal cancer seen in Africa and other less developed regions such as South America, China and areas in Iran, differs from that seen in developed countries.

"The type of oesophageal cancer we find here is called squamous cell carcinoma. In the developed world we find mostly adenocarcinoma - this is oesophageal cancer caused by acid reflux from the stomach. The tumour forms where the oesophagus joins the stomach. Because patients experience frequent heartburn they consult their doctors, and the disease is picked up very easily and early," he explains.

The squamous cell carcinoma causes no early symptoms - tumours grow in a higher region of the oesophagus and patients experience no symptoms until they have difficulty swallowing. "The prognosis for patients who present with this symptom is very poor - less than 6 months," says Prof. Parker.

"This presents a challenge for us, because the adenocarcinoma is well studied, while 'our' form isn't. The cancers of the Western world are well studied, but nobody looks at a cancer of the developing world. The work that we are doing is a niche area for South African scientists," he says.

Education is vital

On a recent research visit to China Prof. Parker saw the benefits of having an educated population and adequate facilities. "There, even in the most remote rural areas, clinics are equipped with a gastroscope that makes early detection and removal of tumours easy, with a high success rate," he says.

"Because of our high illiteracy rate, you need to have people going into the rural areas and educating the population about the disease. There is also the factor of superstition - because people exhibit no symptoms until it's too late for any doctor to do anything for them, they frequently believe it is their visit to the doctor that caused them misfortune. So education is one of the key factors to tackling the long road ahead," he says.

 

October 2002