The Gene Dilemma: Scientists come close to understanding root cause of cancer: Mutations found in one gene are the basis for advances in treatment. Steve Connor reports

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SCIENTISTS are on the threshold of understanding the fundamental cause of cancer - the second biggest killer in Britain after heart disease. One in three people develops cancer and one in four dies of the disease.

New techniques in genetics have enabled researchers to discover the basic trigger that causes cells in the body to multiply uncontrollably when a cancerous tumour grows. Scientists hope the findings will soon result in better cancer treatments that will make death from the disease unlikely.

At the heart of the new insight is the discovery that mutations in one particular gene - called p53 - are found in the tumours of about half the 6.5 million people world-wide who develop cancer each year.

Research into the p53 gene shows it plays a key role in controlling the complex series of events that are part of the normal life cycle of each cell in the body. Mutations in the gene appear to derail the process, causing a cell to multiply out of control into a cancer.

All cells have the potential to divide and multiply, which is how the body grows and replaces worn-out cells. The process is strictly controlled, and it is when this breaks down and a cell divides over and over again that a cancer occurs.

Professor David Lane at Dundee University, who co-discovered the p53 gene in 1979 (its role in cancer was shown only in 1989), believes the latest research is a revolution in cancer knowledge: 'One wouldn't have liked to have said this five or six years ago, but I really think we are very close to understanding the molecular basis of human cancer. We know most of the players and have a broad understanding of what they do. The next stage is the nitty- gritty detail.'

The finding that p53 is involved in at least half the tumours found in virtually all cancers is testimony to its importance. However, Professor Lane believes the proportion of tumours influenced by defects in the gene may be far higher, perhaps 100 per cent.

'I think that's probable. A lot of people wouldn't take that view, but I think it's quite likely.' The reason for this, he believes, is that p53 is at the heart of a series of events which, if damaged, can lead to the uncontrollable multiplication of cells.

Scientists believe that p53 is the guardian of a person's genetic make-up and is involved in a complicated process of vigilance against mutations that can cause cancer. In its normal form, p53 is a cancer suppressor. When it is damaged, the likelihood of a tumourous growth increases significantly.

The enthusiasm in the scientific world about p53 (the 'p' stands for the protein the gene produces) is demonstrated by it, or rather its protein, being voted 'molecule of the year' in 1993 by the journal Science. Its editor, Daniel Koshland, said: 'The excitement generated by it and its fellow tumour suppressors is reaching a crescendo with exhilarating possibilities for prevention and cure of cancer.'

There are two ways that the p53 gene is thought to work in its normal, unmutated form. Professor Lane said: 'One is what we call 'checkpoint' control. It actually checks the cell cycle by saying 'stop dividing, something awful has happened here'. This then would prevent production of cells containing mutations.

'The other action is to take a more extreme view of the situation and say, 'things are so bad we won't be able to repair it. It is much better for the cell to commit suicide'.'

If the gene becomes damaged and unable to function, the effect of this mutation is doubly dangerous because the cell is deprived of p53's beneficial effects and now has a rogue gene that can spur uncontrollable cell growth - the hallmarks of a tumour. 'We believe a cell that lacks normal p53 is somewhat unprotected against cell damage,' Professor Lane said. 'It's all part of the idea that cancer is a multi-step process and you need to accumulate a series of damages before the cell becomes fully cancer-causing. When p53 is not working, that process can probably go faster.'

Understanding just how defects in p53 lead to cancer could also explain some of the mysteries of the disease, such as why people in some occupations or with certain diets are more likely to develop tumours.

American scientists believe they have detected a mutation of p53 which predisposes people to lung cancer triggered by radiation. Writing in tomorrow's edition of the Lancet, they say the mutation may be significant in lung cancers in people subjected to low levels of radiation, including radon-contaminated homes.