What is Li-Fraumeni syndrome? Symptoms, treatments and coping with '90% cancer risk'

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Li-Fraumeni syndrome. (Yahoo Life UK)
Li-Fraumeni syndrome. (Yahoo Life UK)

While Li-Fraumeni syndrome only affects a small number of people in the UK, it can have a big impact on their health and personal lives.

The rare genetic condition is known for increasing people's chance of developing specific types of cancer, with a risk of up to 90% by the age of 60.

Here, we consult the experts to understand exactly what Li-Fraumeni syndrome is, how to cope and the future of treatment.

What is Li-Fraumeni syndrome?

Dr Helen Hanson Li-Fraumeni syndrome. (Supplied)
Dr Helen Hanson is an expert in Li-Fraumeni syndrome. (Supplied)

What is Li-Fraumeni Syndrome?

"Li-Fraumeni syndrome is an inherited cancer predisposition syndrome caused by a mutation or fault in the TP53 gene," says Dr Helen Hanson, a consultant in clinical genetics with a long interest in Li-Fraumeni syndrome.

While you may have heard of an increased cancer risk from mutations in the BRCA1 and BRCA2 genes, you may not have heard about the TP53 gene.

The usual function of the TP53 gene is to protect us from cancer by controlling the growth of cells.

"Everyone has two copies of the TP53 gene, one inherited from their mother and one from their father. Li-Fraumeni syndrome is caused when one copy of the gene has a mutation. If a parent has a TP53 mutation, when they have children there is a one in two or 50% chance any child will inherit the same change. This is known as an 'autosomal dominant' inheritance pattern.

"Sometimes more rarely someone may have a 'de novo' TP53 gene mutation. This means the alteration is not inherited from a parent, but has occurred spontaneously during the process of DNA replication during cell division – normally at a very early stage, in either the eggs or sperm cell, or in a developing embryo."

People with a change in the TP53 gene have Li-Fraumeni syndrome. "In the 1990s, TP53 was identified as the causative gene for LFS," says Dr Hanson.

Researchers estimate there are a few thousand people in the UK with LFS, though only around 500 to 700 people have received a diagnosis, according to Cancer Research UK. "Almost all of them are close to someone else with the condition. Many will have lost someone they love because of it. LFS runs in families," it highlights.

People with Li-Fraumeni have a nine in 10 chance of developing cancer

Most cases of cancer (about nine out of 10) happen by chance, but a few (about one out of 10) happen when someone has inherited an increased risk from a member of their family, the NHS points out.

People with Li-Fraumeni syndrome have a nine in 10 chance of developing specific types of cancer by the age of 60. It has also been reported that for children with a diagnosis of Li-Fraumeni syndrome, one in five can develop cancer before their fifth birthday.

"The lifetime cancer risks are very high. Studies have estimated the risk of developing cancer by age 40 is about 50%," says Dr Hanson.

"We still have much to learn about specific cancer risks and types associated with the exact mutation in the TP53 gene." This includes whether there are any factors that can affect your risk factor.

"Individuals are at risk of developing cancer throughout their lifetime, even if they have had it once or twice before," Dr Hanson adds.

How to get tested for Li-Fraumeni syndrome

You can test for Li-Fraumeni to see if it runs in your family. "Where possible, we always recommend the initial genetic testing in a family is in a person who is affected with cancer. We would recommend genetic testing of the TP53 gene in certain situations as set out by the National test directory [which includes specific criteria]," says Dr Hanson.

"If there is a known history of LFS in a family and the TP53 genetic change is already known, then we would advise family members are referred to their local genetics centres to discuss genetic testing [to see if they have inherited the same mutation]."

"Deciding to have genetic testing is a personal decision and can be a difficult and complex process," the NHS outlines. "Not everyone will choose to have genetic testing. If you decide against it, you may still be eligible to have regular screening and we will discuss this with you."

The health service adds, "Before we offer you a predictive test [to see if you have inherited the gene mutation] we discuss with you what the test could mean for you and your family. Your genetics clinician will talk to you about the many things to consider before deciding. You can read our suggestions to help you decide here." This includes the timing of testing, the psychological impact of knowing, coping strategies and next steps.

Treatment for Li-Fraumeni syndrome

"There is currently no cure for Li-Fraumeni syndrome – you can't correct the TP53 gene alteration. Therefore increased cancer surveillance to detect cancer at an early stage is recommended for individuals who have the condition from birth," says Dr Hanson.

"This includes an annual brain MRI, annual whole body MRI from birth, three-four monthly abdominal ultrasounds in childhood and a breast MRI in women from the age of 20. Some women may choose a double mastectomy to help reduce their risk of breast cancer."

On a more optimistic note, Dr Hanson highlights a research trial called the Metformin in Li-Fraumeni study (MILI) that has recently opened, which is looking at using metformin, a drug normally used for people with diabetes, to evaluate if this might help lower the chance of cancers developing in individuals with LFS.

The future of Li-Fraumeni

 Sarah Blagden. (Supplied)
Professor Sarah Blagden is leading the MILI trial. (Supplied)

Professor of medical oncology Sarah Blagden, University of Oxford, who is leading the research (open until 2027) says, "The idea for the study came from research conducted in the USA showing that cell metabolism [reactions] was higher in people with LFS and if mice with LFS were given metformin (to turn their metabolism down) they were slower to develop cancer. Other studies have already shown metformin works as a cancer preventive (such as in preventing colorectal cancer), so the aim of the MILI study is to answer this question definitively in people with LFS."

If metformin proves to be beneficial in her research study, Blagden's team is hoping to seek regulatory approval so it can be used for all adults with LFS. "We have already had feedback that the prospect of having an intervention will motivate more people from LFS families to have genetic testing."

If the anti-diabetic drug could be used to help with prevention, then at what stage? "Any time after LFS diagnosis, the sooner the better."

Treatment options if you develop cancer

Having a TP53 mutation may affect treatment options if you develop cancer, so it is important to share this information with your medical team, according to the NHS.

"These cancers are treated in the same way as other cancers depending on the type and prognosis. Where possible, radiotherapy should be avoided, but it is sometimes necessary as it is the best treatment for the current cancer. As Li-Fraumeni syndrome is a rare condition, treatment can’t easily be generalised and each case would be treated individually," Dr Hanson points out.

Balancing Li-Fraumeni with grief

For some living with Li-Fraumeni syndrome, they will already have lost family members to cancer.

"Whether you’re full of feelings, numb or somewhere in between, it's important to find a way to acknowledge or voice this," says Georgina Sturmer, counsellor, MBACP. "This might be in therapy, or with a trusted friend or relative, or perhaps in some creative way."

She emphasises that there is no linear path to coping. "We might have easier periods and more challenging periods. Keeping track of how we are feeling and how we are coping will help us to notice specific triggers or events that might make things more difficult. It might be helpful to develop specific methods or allow moments to express our grief, and mourn for those we have lost."

In terms of balancing this with living with a rare genetic condition, she adds, "It's your choice as to how much of your personal story you wish to share with those around you. Sometimes you might feel as if you want to be surrounded by people who understand, and sometimes you might wish to set it aside so your grief and worries don’t always feel part of your identity."

To find out more about what Li-Fraumeni syndrome is like in reality, read Sophie Power's story here:

Living with Li-Fraumeni syndrome: 'I've had cancer twice and lost three family members to the disease'