A question that crops up again and again is how many people with Li Fraumeni Syndrome (LFS) are there in the UK? While it’s an easy question to ask, it’s not so easy to find an answer. The fact is that nobody knows for sure but we can make some educated guesses based on estimates of how often TP53 mutations occur. In the past I have used a figure for the UK of 1/10000 to 1/25000, which gives a theoretical count of mutation carriers in the range 6400 – 2560. That’s an awful lot of people when you think about it. And of course it does not include the 30% or so of people with LFS or Li Fraumeni-like (LFL) Syndrome who do not have a TP53 mutation.
I got slightly different estimates from a couple of the UK’s leading LFS experts. One suggested the rate of mutation carriers could be in the range 1/5000 to 1/20000, which means a population of carriers of between 12800 to 3200. Another very experienced clinician estimated 1/5000 to 1/10000, giving a UK population of 12800 to 6400. If we took a simple average of those numbers we’d come up with around 4300 in the population, add to that those without a mutation and you could easily have 5500 people in the UK who have LFS.
Of course when we’re asking the ‘how many people’ question what we’re often interested in is how many people are actually diagnosed? That is how many have been tested and formally diagnosed as having LFS or LFL? Again, nobody knows for sure. According to one of our experts the number could well be around 400 – 500. Our other expert suggested that only about 10% of people with LFS are formally diagnosed. Around 90% of those who have the condition don’t know about it. That’s an awful lot of people suffering early onset or repeat cancers, often with dire family histories, and not knowing why.
ROBERT MEIKLEHAM
AS THINGS STAND IN SCOTLAND AT THE MOMENT,THERE IS NO SUPPORT NETWORK AND GENETICS COUNCILLORS ARE OF NO HELP.AS MOST THINGS YOU CAN GOOGLE FOR ANSWERS.NOT HELPFUL AS YOU NEED PEOPLE TO TALK TO AS A FAMILY AS WELL AS INDIVIDUALLY.HEALTH BOARDS NEED TO BE MORE AWARE AND HELPFUL.
Pan
I agree Robert. We’ve got a lot of work to do to change things.
ROBERT MEIKLEHAM
HOW DO WE ADDRESS THIS WITH THE HEALTH BOARD
DO THE PARENTS HAVE ACCESS TO COUNSELLING
DO WE BRING THIS UP WITH GP OR HOSPITAL
CONSULTANTS
AS MYSELF I WORRY ABOUT MY DAUGHTER AND HOW TO DEAL WITH THE SITUATION
Pan
Robert, you should be able to access counselling via your genetics clinic. And that can include counselling for you, your daughter or other family members.
Charlotte
i agree the UK needs to be educated more about this gene. i have LFS , my daughter is being tested soon, my late mother and late sister had it, my mums father and brother had it . my brother has it and so does my other uncle. i doesnt affect all members of the family which i find really unfair but obviously im happy for those who dont have it. its a wicked gene. if you have you get mri scans every year for men they dont really monitor which is bad in my eyes. females are watched very close every year. i have two mri’s and one mammogram every year. i used to have abdominal scans when younger which has stopped which i feel is wrong, they thought abdominal scans are for childhood cancers but the usa know more facts and im still at risk in the abdominal area!
Pan
These are valid questions – there still seems to be a lot of variation in how and when people get scanned. This is going to be a topic at our LFS UK 2016 meeting on June 18th this year.
Helry
P53 with variant of uncertain signifance has anyone information on this
Pan
Hi. This means that a person has got a mutation in the TP53 gene but doctors don’t know if it’s a mutation that’s associated with an increased cancer risk or not. In some cases there are TP53 mutations which are associated with an increased risk of specific cancers (osteosarcoma for example), but sometimes there are mutations which haven’t been seen before or which haven’t been shown to be related to cancer. If the person who has one of these mutations has got a family history full of cancer then you’d probably be safe to assume that they’re at increased risk of the disease.
helry
Pan… Is it a fact that if a family member is diagnosed with LFS and it is a variant of uncertain signifance ,other currently cancer free family members are not offered a test for P53, unless they develop a cancer (the family history is very signifant in this situation)
Pan
There’s a set of criteria that is recommended by the Institute of Cancer Research for deciding who to test. A family history of cancer is taken into account, but some of this depends on which particular cancers people have had and at what age. We describe this here: https://www.tp53.co.uk/tp53-testing/
But keep in mind that these are recommendations only. There is a certain amount of scope given to genetics specialists on who to test. Do you know the actual mutation?
helry
No I dont know the exact P53 mutation,unfortunely family members have also tested positive for a second gene defect that causes kidney cancer called fumarate hydrase deciciency as well as a P53 germline mutation,as this is a second gene defect we were told there is no connection between it and p53,just I suppose the cancer risk is even higher
Of 7 siblings 3 have died of renal cancer (papillary and clear cell), 1 of sarcoma/leukaemia all since 2011 ages 48-60,a sister living age 47 has been diagnosed with breast cancer (Her2+) a nephew has died of a brain tumour age 33 and his brother has has extensive brain surgery for a tumour also
My mother and her 2 siblings died of brain & renal cancer,<52yrs
So we are confused and fearful for our children. and just trying to understand all this.. thank you for replies
Pan
That’s a horrendous family history. The actual details of the mutations aren’t that important. The main thing is that you’ve been diagnosed with LFS. At our meeting in June we’ll make sure that there’s time for people to ask questions and make their voices heard.
Helen Ryder
Pan
Sorry to have missed out on June 18
Of the three of us alive out of 7 siblings,my younger sister P53 positive had a mastectomy in June ,the genetics here only tested her after she developed the cancer.
My other sister now has uterine changes on an MRI and is awaiting plans,she is not tested to date for p53 as yet
I dont understand why we wont be tested until a cancer develops? Is there anyway we could get tested elsewhere?
H
Pan
Hi Helen. Where are you in the UK? If one of your sisters has tested positive for a germline TP53 mutation then that should trigger a test for all her siblings and any children. Have you been referred to a cancer genetics clinic?
Pan
Helen Ryder
Thank you Pan
We live in the West of ireland,we are under genetics since Sept 2013,but feel isolated and alone.
My sisters recent report June16
“Molecular analysis shows presence of the familial missence varient c.800G>A,p.(Arg267Gin)in the TP53 gene” in the heterozygous state, further loss of heterozygosity studies are awaited on her tissue sample
A variant of uncertain significance is reported ,but the family history is very significant 4 out of 7 siblings dead since Aug 2013, 2 more with cancer and me currently not diagnosed with cancer yet ,2 nephews 1 dead from a brain tumour,and his brother alive 10 years after aggressive brain surgery & radiation treatment for a tumour
H
Pan
Sorry to hear that you feel isolated like that. I think everyone who’s got LFS has felt like that. I agree completely about your family history – it’s clearly significant. Everything you need to know is there. The ‘variant of unknown significance’ just means that there isn’t enough data on that particular mutation for them to definitely say that it’s associated with an increased cancer risk or not. But given your family history it looks like there’s a clear increase in cancer risk. What happens is that over time enough people with the same mutation show up and then they can definitely say that we know that this variant is pathogenic or not. When I look up that particular mutation on the IARC TP53 database it does show up though, so it’s not the first time that particular mutation has shown up. It looks to me like there’s good reason for all of you to be tested. Can you not ask for a second opinion?
helen ryder
Pan,Would a TP53 registry include Ireland
Pan
Hi Helen. Personally I would love a global registry. LFS is so rare that even a global registry wouldn’t be huge. However there are all kinds of issues around who hosts a registry, who curates the data, what kinds of controls are in place over data access etc. In practice we might have to start with a UK-based system and then expand. I hope we can have a system that does allow us the possibility to add individuals outside the UK, particularly from other parts of Europe.
helen
Pan Does the George Panziarka TP53 Trust link with a US organisation called PROMPT(Prospective Registry Of MultiPlex Testing)
Pan
Hi Helen. We’ve not had any direct contact. Would be interested in finding out more. Have you been in touch with them?