Scientists find two routes to mouth cancer

Cancer Research UK

Cancer Research UK scientists have discovered mouth cancer can develop along two distinct pathways, an aggressive or less aggressive route, reveals a study published in Cancer Research* today (Tuesday).

The research lays the foundations for further studies that could help to improve the management of pre-cancerous lesions and possibly prevent the development of the disease in the future. The researchers from Cancer Research UK’s Beatson Institute for Cancer Research in Glasgow took samples from the mouths of 19 people with pre-cancerous lesions, or spots, 16 patients with mouth cancer and four normal mouths. They compared these samples, each one made up from thousands of cells, in an attempt to find out if the disease develops in more than one way.

The researchers identified two different routes by which mouth cancer develops, resulting in ‘mortal’ and ‘immortal’ tumour cells when they are grown in the laboratory. ‘Mortal’ and ‘immortal’ cells are genetically very different. ‘Mortal’ cells have a limited lifespan and so will exhaust themselves as they develop into a tumour, being less likely to spread or recur following treatment. ‘Immortal’ cells on the other hand are much more resilient and will keep on dividing, making them more likely to spread and to cause a recurrence - a major characteristic of aggressive disease.

They found that faults in the p53 gene and missing expression of the p16 gene were closely associated with ‘immortal’, aggressive tumours. Importantly, these same changes were also found in pre-cancerous cells, which grew in laboratory cultures as ‘immortal’ cells. When it is working normally, the p53 gene stops damaged cells dividing and should stop cancers growing, which is probably why faults were found in the p53 gene in ‘immortal’ cells rather than in ‘mortal’ ones. The p16 gene helps to control the cell regulation process and can prevent cancer from developing - expression of this was missing from most of the more aggressive mouth cancer cells.

Lead researcher Professor Paul Harrison, from Cancer Research UK’s Beatson Institute, said: “We found that many of the molecular changes found in ‘mortal’ and ‘immortal’ cancers are also found in their respective pre-cancerous lesions, which suggests that mouth cancer forms in different ways.”

Mouth cancer patients often develop a series of pre-cancerous lesions over a number of years, due to damaged DNA frequently caused by prolonged tobacco and alcohol use. Previously scientists thought all mouth cancers developed via a single route - from pre-cancer to mouth cancer as the DNA in mouth cancer cells’ progressively accumulated more damage. This is the first time scientists have established why some types of pre-cancerous lesions are more likely to develop into more aggressive cancers. This could be important because using current tests, it is impossible to predict which pre-cancers will actually develop into cancer.

Professor Harrison goes on to explain: “The data we collected provide strong evidence for the first time that some mouth cancer tumours are more aggressive than others and are therefore linked to poorer patient survival. We hope in the future that these findings will allow us to discover early on who needs urgent treatment and possibly offer new methods of preventing the disease.”

Professor John Toy, medical director at Cancer Research UK, said: “Cases of mouth cancer in the UK have risen by a quarter over the past 10 years so these are valuable findings that will help scientists gain a clearer understanding the ways the disease can develop and progress.

“1,600 people die every year from the disease and Cancer Research UK has launched an awareness campaign ‘Open Up to Mouth Cancer’ to encourage people to spot the early signs of the disease and reduce their risk. The most common indicators of mouth cancer are sores, ulcers, red or white patches and unexplained pain in the mouth or ear. Less common signs include a lump in the neck, a persistent sore throat or difficulty swallowing. If any of these persists for more than three weeks they need to be checked out by a doctor or dentist.”

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Notes to Editor

Divergent routes to oral cancer. Hunter et al. (2006). Cancer Research. Vol 66, Issue 15.

This work was supported by Cancer Research UK, the University of Glasgow, Strathclyde University and a grant from the Engineering and Physical Sciences Research Council (EPSRC).

A limited number of case studies are available for interview.

Mouth cancer

Mouth cancer can develop in any part of the mouth including the tongue, gums, lining of the mouth, lips and upper part of the throat.

Around 4,400 people are diagnosed with mouth cancer each year in the UK and around 1,600 people die from the disease each year. In Scotland, the incidence rate is about 50 per cent higher than in England.

Nearly twice as many men get mouth cancer than women. However, this difference is narrowing, and the sex ratio has decreased rapidly from 5:1 fifty years ago to less than 2:1 today.

Rates of mouth cancer have doubled in men in their 40s and 50s since 1975. Most cases of mouth cancer are already at a late stage when diagnosed, and may already have spread to other parts of the body.

Many patients are left with permanent side effects as a result of treatment. These can be severe, and affect eating, drinking, speaking and appearance.

Most cases of mouth cancer are preventable.

The causes of mouth cancer:

  • smoking tobacco - including pipes and cigars
  • chewing tobacco
  • Betel quid or paan masala
  • regularly drinking more than 3 - 4 units of alcohol a day (2-3 for a woman)

People who smoke or chew tobacco AND drink too much, have a much higher risk of getting mouth cancer. As many as 3 out of 4 (75 per cent) mouth cancers diagnosed develop in tobacco users who drink

The commonest symptoms of mouth cancer are:

  • A sore or ulcer in the mouth that does not heal
  • Discomfort or pain in the mouth that does not go away

It can also cause:

  • White patches anywhere in your mouth (leukoplakia)
  • Red patches anywhere in your mouth (erythroplakia)
  • A lump on the lip, tongue or in the mouth or throat
  • Pain when chewing or swallowing
  • A feeling that something is caught in the throat
  • Unusual bleeding or numbness in the mouth
  • Loose teeth or dentures feeling uncomfortable and not fitting properly
  • A change in your voice or speech problems
  • Weight loss
  • A lump in the neck

White patches (leukoplakia) or red patches (erythroplakia) can be signs of pre-malignancy. Pre-malignant cells are abnormal, but they are not yet cancer. If left untreated, pre-malignancy can go on to develop into cancer, especially erythroplakias. But if you get the condition treated, cancer can be prevented from developing.

If you notice any of these changes and they last longer than three weeks, tell your doctor or dentist without delay. Usually they are not caused by cancer but it is better to play safe. Regular dental check-ups will help detect mouth cancer in the early stages.

Cancer Research UK is running a national campaign for mouth cancer called ‘Open Up to Mouth Cancer’ with funding from the Department of Health. The campaign aims to raise awareness of the risks and symptoms of mouth cancer, and the importance of early detection.

Open Up to Mouth Cancer is part of Cancer Research UK’s Reduce the Risk campaign - launched in January 2005 - which encourages people to take positive steps in five areas to reduce their risk of cancer: Stop smoking, Stay in shape, Eat and drink healthily, Be SunSmart and Look after number one - know your body and go for screening when invited.

More about Cancer Research UK’s mouth cancer campaign can be found at Open up to mouth cancer

Visit our patient information website CancerHelp UK for clear, easy to understand information about cancer and cancer treatments.

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