P53 Information Sheet

Factsheet on P53.

We already know smoking causes lung cancer. Finally, we have the first direct proof of exactly how it does. It all comes about because of a fascinating and important gene known as p53.

The p53 gene, which is found in the nucleus of every cell in the human body, is known as "the guardian of the genome". The genome is the technical name of genetic information: DNA. Every day, DNA in many of our cells copies itself, and every day a few errors are made in this process. The new cells created by these mistakes have the potential to become cancerous. One of p53's main roles is to clean up those changes and errors within the cell. Obviously, a p53 gene which does not work properly would leave a cell, and ultimately a human body, highly susceptible to cancer. (1)

A damaged p53 gene is found in at least half of all cancers.(2,3) p53 is damaged in a very specific way in about 60% of people who smoke and develop lung cancer.(4) Some components of cigarette smoke react chemically with DNA. If such damaged DNA is not repaired, mistakes are introduced when the damaged DNA replicates during cell division. In this way, a modified cell population which is not responsive to normal growth control may develop and ultimately evolve into cancer.

Scientists from California and Texas made the direct genetic link between smoking and lung cancer in 1996 when they proved that a carcinogen, benzopyrene which is found in high concentrations in cigarette smoke, directly damages p53.(4) They showed that cigarette smoke leaves its distinctive signature on p53. There is no doubt at all that smoking damages p53, and this allows lung cancer to develop.

There is no simple test to see what condition somebody's p53 genes may be in.

Diagram of how P53 gene is damaged

References

1. Nature 1992;358:15-16
2. Cancer Research 1994;54:4855-4878
3. British Journal of Cancer 1994;69:409-416.
4. Science 1996;274:430-432.

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