We need early diagnosis of LFS – not just cancer


There is a recurring theme in many stories from LFS families who contact the TP53 Trust. They describe the moment when someone in the family is finally diagnosed with LFS – at that moment things start to make sense. There has usually been a grim family history before that diagnosis – a history of individuals being struck with cancer at a young age, of strange patterns of rare sarcomas and some who have suffered two, three or even more different primary cancers. In the absence of the LFS diagnosis this has always been put down to bad luck – something that seems more like a curse than the workings of chance alone.I can remember being told by one doctor that the odds of my first wife and my son getting cancer in quick succession was bad luck – with the same kind of odds as winning the lottery. Later, when George was diagnosed with LFS it all made sense. And I’ve heard the same thing again and again. The LFS diagnosis, when it finally comes provides an explanation for the sequence of horror stories.

For people with LFS, who are born without the in-built anticancer protection provided by the TP53 gene, the life-time risk of developing cancer is around 90%. In particular the syndrome is characterised by early onset breast cancer and rare childhood cancers such as soft tissue and bone sarcomas. It is also not uncommon for people to survive one cancer only to go on to develop a different form of the disease at a later point. And we know this not just because of academic research but from the lived experience of our own families and families like ours.

In this scenario catching cancer early is essential – that’s why there is so much effort spent on getting regular scanning and surveillance. It’s what the SIGNIFY trial and others like it are all about. But all this depends on a formal LFS diagnosis to trigger that state of vigilance. The fact is that while the criteria for germline TP53 testing have improved in recent years, and genetic testing technology moved on considerably, many families with LFS remain undiagnosed. And let’s be honest, the criteria for TP53 testing are complex and in some cases may not be triggered until a child develops a second or third malignancy.
There is an argument to be made that all children diagnosed with cancer should be germ-line tested – not only will this identify those individuals suffering from LFS or other cancer predisposition syndrome, it may also shed new light on a disease that is primarily associated with older age groups.

In the past there have been objections to routine genetic testing for LFS and other conditions. Some of this was associated with cost, but with the improvements in technology mean this objection is no longer sustainable. A more fundamental objection has been that testing and subsequent diagnosis imposes additional psychological distress on affected individuals – particularly as there is no cure for a disease like LFS. However, for many families a diagnosis both provides an explanation for the pattern of disease and may open the doors to improved access to doctors and testing when cancer is suspected. Secondly, while there is no cure for the underlying TP53 mutation, there is increasing evidence that there may be other factors which impact on the elevated cancer risk. There may be preventative measures, including the use of drugs, dietary and lifestyle interventions which may reduce the risk in affected individuals.While we need more research to prove this is true or not, we also need to reliably identify how many children with cancer are suffering because of a mutated TP53, PTEN or other cancer-predisposition gene.

4 Responses

  1. verity easton
    | Reply

    Great article. I have thought for some time that routine p53 test should be offered to all children diagnosed with cancer. A part of me feels that LFS is not as rare as we think and that many more people have it but are undiagnosed.

    • Pan
      | Reply

      Thanks Verity. And thanks too for being the first person to comment on a blog at the new site! One of the questions that we often get asked is ‘how many people have got LFS in the UK?’ And the answer is we don’t know. Like you I suspect that there are more families affected than are currently diagnosed.

  2. lisa courtney
    | Reply

    I have been researching types of cancer and came along li fraumeni. My mum passed away of leiyomyosarcoma which is a rare form. My brother had an ependymoma tumour at 15 and now has tumours down his spine and more recently in his head.
    My son was born with a lymphangioma which is another rare type of tumour but benign. I have para ovarian growths and had numerous types of benign tumours all of which can appear as malignant.
    I am really keen to learn about li fraumeni and would like to see if i have a TP53 problem and if so , help with research.

    • Pan
      | Reply

      Hi Lisa. Have any of you been tested for a TP53 gene defect? It seems to me with your family history there’s enough to warrant a test. Are you in the UK?

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