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.

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.