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In 1969, two Doctors called Dr Li and Dr Fraumeni reviewed all the cases of childhood sarcoma (cancer of the bone or soft tissue such as muscle), in their hospital. They noticed that in some families there was a higher number of relatives affected with cancer than would be expected by chance. Further study of these families showed there was an increased risk for sarcoma, breast, brain and adrenocortical cancer (cancer of the glands on the top of the kidneys). The families were described using clinical criteria and these became known as the “Classic Li Fraumeni Syndrome” criteria. In 1990, gene faults (mutations) in a gene called TP53 were found to be the cause of Li Fraumeni syndrome. Since then, TP53 gene mutations have been found in other families who do not meet the original criteria of Li and Fraumeni. The risks of cancer in some of these families can be different and/or lower than the very high cancer risks in Li Fraumeni syndrome. The exact risks remain unclear at present but this is an area of active research. As more information is gathered the cancer risks associated with different TP53 mutations will become clearer.

If a person with a TP53 gene mutation develops cancer they are generally treated in the same way as any other cancer patient. There are currently no therapies that are specifically designed for people with Li Fraumeni syndrome or a TP53 gene mutation.

This is a controversial area where there are different opinions amongst doctors. The advice from some has been that radiotherapy should be avoided for people with a TP53 gene mutation. This was because of a suggestion that people with a TP53 gene mutation might be at increased risk of developing a future cancer in the radiation field. However, there is currently no conclusive evidence for this. Therefore many doctors, including those at the Royal Marsden Hospital and Institute of Cancer Research, believe one should give the best available treatment for the existing cancer, including radiotherapy if required, rather than giving sub-optimal treatment for the existing cancer to try to reduce the theoretical increased risk of a future treatment-related cancer.

There is no evidence to suggest that specific diets or exercise programs can prevent people with Li Fraumeni syndrome or a TP53 gene mutation from developing cancer. However, the general guidelines that are recommended for cancer prevention would still apply:

  1. Eat a healthy balanced diet including at least five portions of fruit and vegetables per day
  2. Do not smoke
  3. Do not drink alcohol in excess. Women should not drink more than 2-3 units per day and men should not drink more than 3-4 units per day.
  4. Maintain a healthy weight.
  5. Keep active.
  6. Protect skin from sun damage.
The test involves giving a blood sample. It is possible to use a saliva sample if a blood sample is not obtainable, but this is not recommended. The blood sample is sent to a laboratory and DNA is extracted from the blood cells. The genetic code of the TP53 gene is read from the DNA to see if there is a mutation. In the UK, the result currently takes about 8 weeks to be ready.
There are a number of Regional Clinical Genetics services across the UK and a Specialist Cancer Genetics unit at the Royal Marsden in London. For details see http://www.bshg.org.uk/genetic_centres/uk_genetic_centres.htm. All Regional Genetics centres have expertise in inherited cancer predisposition syndromes and will co-ordinate the initial genetic testing, predictive genetic testing in other family members and advise on appropriate screening and follow-up.
Finding a cure for Li-Fraumeni syndrome and TP53 mutations is not an easy task, as the genetic mutation in TP53 is present in every cell in the body. There is ongoing research in multiple areas, including searching for drugs that will specifically target cancers in TP53 gene carriers, similar to the development of PARP inhibitors for BRCA1 and BRCA2 carriers.
At present in the UK, no targeted screening is recommended or of proven benefit for any cancers other than breast cancer.
Women with TP53 gene mutations should practice breast self-awareness and examination. They should also have access to annual MRI scans of the breasts from age 20-50 years and annual mammograms from age 30-50 years. In addition some women may wish to consider risk-reducing mastectomy (removal of both breasts, with the option to have reconstruction), to reduce their breast cancer risk. This is a very personal decision and should involve consultation with your Genetics team and a recommended Breast Surgeon.
There are currently no blood tests that are available to detect other TP53 associated cancers (breast, brain, adrenocortical and sarcoma) at an early stage.

 

Text reviewed by Dr Helen Hanson, Institute of Cancer Research.