Major Risk Factor For Cervical Cancer Found

May 21, 1998

Scientists have found that women who carry a particular variation of the tumour suppressor gene p53 are seven times more likely to develop cervical cancer that those who do not. The researchers' findings are published today (21 May 1998) in the science journal Nature*.

The work was carried out by scientists from the Imperial Cancer Research Fund (ICRF) Skin Tumour Laboratory and Department of Medical Microbiology at St Bartholomew's and Royal London Hospital School of Medicine and Dentistry, London, the International Centre for Genetic Engineering and Biotechnology, Italy, and the Institute for Parasitology and McGill Cancer Centre, Quebec, Canada.

Doctors already know that infection by certain types of the Human Papillomavirus (HPV) is almost essential for cervical cancer to develop. Major advances have been made in understanding how these viruses cause cancer. However, much less in known about how an individuals' genetic makeup may contribute to cervical cancer development.

P53 is a key control point in the body's defence against tumour formation. It protects the genetic information in the cells from things which can damage them such as ultra violet radiation or certain chemicals. If p53 goes wrong then a cell has a greater chance of becoming cancerous.

Dr Alan Storey, leader of the ICRF research team, explained: "P53 is often defective in many forms of cancer but in cancers caused by the Human Papillomavirus (HPV) it is usually normal. Instead, HPV produces a protein, called E6, which stops p53 from working correctly."

People can carry one of two variations of the p53 gene, p53Arg or p53Pro. The researchers found that p53Arg is more easily inactivated by the HPV protein. This suggested that people who carry only p53Arg might be less well protected against the effects of HPV.

Said Dr Storey: "We found that cervical cancers resulting from HPV infection were significantly more likely to occur in women who had only p53Arg. This implies that p53Arg is a major risk factor for cervical cancer."

The research team now plans to do further, larger, studies in different populations to confirm and extend their findings.

"In the future testing for p53 status may prove to be another useful tool in assessing a woman's risk for developing cervical cancer," commented Dr Storey.

The findings also have implications for certain skin cancers which are linked to HPV infection and exposure to ultra-violet radiation. Organ transplant patients who, because they take drugs to suppress their immune systems, have a high risk of developing the skin cancer squamous cell carcinoma(SCC). The SCCs which occur in these patients are linked to ultra-violet radiation and HPV infection and appear five to 10 years after the transplant.

The study showed that the Arg variant conferred a strong susceptibility to SCC in these patients. Seventy five per cent of the transplant patients with SCC had p53Arg only and 25 per cent had p53Arg/Pro.

"SCC in transplant patients is a very big clinical problem," said Professor Irene Leigh, head of the ICRF Skin Tumour Laboratory. "Many of these patients are particularly vulnerable to skin cancer and can develop many tumours which often require extensive surgery. These findings indicate that those patients who have p53Arg are at greater risk of developing SCC and we shall be carrying out further research in this area."

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*Role of a p53 polymorphism in the development of human papillomavirus-associated cancer. Nature 21 May 1998.

(ends)

Imperial Cancer Research Fund - Background Brief

The Imperial Cancer Research Fund is dedicated to the understanding, prevention, treatment and cure of all forms of cancer. Its scientists and doctors are at the forefront of the worldwide effort to defeat the disease. The charity relies almost totally on voluntary funding to carry out its vital work.

Web site: www.icnet.uk

FURTHER INFORMATION:
Christine Suggars. Tel: +44-171-269-3614 or +44-171-242-0200
-end-


Imperial Cancer Research Fund

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