What is LFS?
The diagnosis of Li Fraumeni Syndrome (LFS) can be devastating. Sometimes it comes totally unexpectedly, sometimes a person suspects that there is a reason for several people in the family getting cancer. But what is LFS, what are the implications of having it and what is being done to keep those who have it healthy?
• Li-Fraumeni Syndrome is one of a number of rare cancer predisposition syndromes. These are genetic conditions which increase the chance of a person getting cancer.
• Genes contain the instructions for cells to build the proteins which are needed for us to live.
• LFS is associated with a gene called TP53, which creates an anti-cancer protein called p53.
Normally, when a cell starts to become cancerous the p53 protein kicks in and stops this process so that cancer does not form. However, in people born with a fault in the TP53 gene – sometimes called a ‘mutation’ or ‘pathogenic variant’ – the p53 protein is also faulty and cannot stop the cancer developing. This means that people with LFS are at high risk of developing cancer over their lifetime.
• Most people with LFS inherit the disease from a parent.
• Sometimes a person can be born with LFS without either parent having the condition. This is called ‘de novo’. This occurs when the fault in the TP53 gene happens in the foetus and not from the mum or dad.
• A person with LFS has a 50% chance of passing it on to their child.
Mostly, families with LFS have many cases of cancer in their family tree, with the disease passed down through the generations. In some families, no fault in the TP53 gene is detected, but they have very similar family histories of cancer to those who do have a TP53 pathogenic variant and may still be given a diagnosis of LFS by their Doctors if certain clinical criteria are reached.
What are my chances of getting cancer?
The statistics on cancer risk have been compiled from historical cases of LFS when genetic testing was expensive and not performed routinely. This meant that most of the people diagnosed with LFS had already suffered one or more cancers. In many cases people were not tested until their third cancer. In that scenario it should not be a surprise that the cancer risk appears incredibly high. Those with LFS but without cancer would not have been counted. As time goes on and more people without cancer are diagnosed with LFS it is expected that the cancer incidence statistics will decrease.
Also, there are a wide range of TP53 variants in people with LFS, and some variants may be more associated with cancer risk than others. It is important to keep in mind that the statistics for LFS apply to the group as a whole and cannot be taken as applying directly to any one individual or variant. Even within families that share the same TP53 variant there are differences in cancer incidence, with some affected individuals not getting cancer at all and some developing it early.
Finally, it is important to keep in mind that our understanding of LFS is constantly expanding. We are learning much more about how different TP53 variants impact cancer risk, how cancers form and develop and how best to manage LFS. We are exploring ways to reduce the risk of cancer ever starting. The published statistics are shocking and depressing – but they do not paint the entire picture of life with LFS.
With those caveats in mind, you’ll see a range of figures quoted via search engines on the internet. The most commonly quoted figure is the life-time risk of developing one or more cancers by the age of 70, with a historical figure of 70% in men and 80%-90% in women (due to their increased risk of breast cancer). The risk of a second cancer is around 40%-50%. The age of cancer incidence varies, with a peak in adolescence/early adulthood.
Remember, over time we fully expect that the headline statistics for cancer risks in people with LFS will change for the better. But for now, treat the figures that are published as worse case scenarios from historical records.
What does having LFS mean for my health?
Surveillance, also called screening, is extremely important for people with LFS. The aim of surveillance is to catch cancer early so that it can be treated effectively. This means regular check-ups, including whole-body MRIs and physical examinations during childhood and adulthood. The management of LFS is based on a clear protocol that all people diagnosed with LFS should receive [add link here].
Because of the high risk of breast cancer, women with LFS may be offered risk-reducing mastectomy (surgery to remove breast tissue), to lower the chance of developing breast cancer.
People with LFS are also advised to live a healthy lifestyle – to eat a varied diet, to exercise, to avoid smoking and to try and reduce stress. At the moment there are no studies which show that any particular diets or lifestyles can reduce the risk of cancer in someone with LFS – although this is a subject that we would all dearly want to see explored more fully.
It is important to remember that not everyone with LFS will become ill – there are some who live to old age without once getting cancer.
What does having LFS mean for my family?
If you are the first person in your family to be diagnosed with LFS, then all your first-degree relatives (parents, siblings and children) should consider being tested to see if they have the same TP53 variant as you do. It may be difficult to share this information with your relatives, but strategies for doing this, as well as who should be informed, will be discussed with you in detail by the cancer genetics team. Not everyone may choose to be tested, but it is important that every adult who may also have the TP53 variant is informed of the risk and they can make their own decisions about testing. Decisions about testing children obviously require great care.
The future?
When you are first diagnosed with LFS you are faced with a barrage of information, particularly if you are diagnosed whilst you are being treated for cancer. LFS is rare and you may feel that you and your family are the only ones affected. But you are not alone. There is a whole community of people who have been through this and are willing and able to share.
There is a hive of activity involving a broad range of doctors, scientists and people with LFS to improve long-term health so that people with LFS can live unburdened by fear, worry and the threat of cancer.