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Li-Fraumeni syndrome is a hereditary cancer syndrome.
Li-Fraumeni syndrome (LFS) is a hereditary condition associated with higher risks of a range of childhood- and adult-onset cancers. This condition can be passed down in a family and is caused by a faulty (disease-causing)
The most common types of cancers associated with LFS include sarcomas (cancers arising from connective tissue) and:
The estimated frequency of LFS ranges between
one in 5,000 to 20,000 people. These rates may change as more information is known.
Hereditary cancer makes up about 5-10% of all cases of cancer. Some genes function to protect us from cancer. When they are not working well, it causes hereditary cancer. We refer to genes that are not working well as faulty genes.
Individuals who carry a faulty cancer gene(s) have a higher chance of developing certain cancers over their lifetime compared to the general population. The types of cancers that they may be at increased risk of will depend on the gene(s) involved.
If you have a faulty cancer gene, you may be at increased risk of developing certain cancers. As genes are shared among family, other family members may have inherited the faulty gene and may be at increased risk of cancer too.
Genetic testing is offered to individuals where a hereditary cause of their personal and/or family history of cancer is suspected.
Genes contain the instructions that our body reads to carry out different functions. Genetic testing involves analysing your genes to understand if there are faults (i.e., mutations) that may increase the risk of diseases like cancer.
Hereditary cancer accounts for up to 10% of all cases of cancer.
There are 3 types of results you may receive:
The risk of other cancers including leukaemia, Wilms tumour, neuroblastoma, and lung, colorectal, stomach and pancreatic cancers may also be increased (risk figures not quantified).
Note: The conditions associated with LFS and their risk estimates may change as more information is available. Published literature may overestimate cancer risks. These figures are based on retrospective analysis which may be biased towards families with an excess of cancer diagnoses.
LFS follows a
dominant inheritance pattern. This means that individuals who have one faulty copy of the
TP53 gene have an increased risk of cancer. It can affect both males and females.
Everyone has 2 copies of each gene in their body’s cells:
You should consider genetic testing if you or your family members meet one or more of the following criteria: 1. Sarcoma diagnosed before the age of 45 2. Sarcoma diagnosed at any age, with a relative diagnosed with cancer before the age of 45 or a sarcoma diagnosed at any age 3. Breast cancer diagnosed before the age of 31 4. A LFS-related condition* diagnosed before the age of 46 and a family history of cancer 5. Two or more LFS-related conditions* in the same individual 6. Two or more family members on the same side of the family with a LFS-related condition* before the age of 56 7. Adrenocortical cancer or rhabdomyosarcoma at any age 8. Tumour in the choroid plexus (membrane surrounding the brain) at any age 9. A previously identified faulty
TP53 gene in the family 10. A
TP53 gene fault identified at high frequency on tumour testing
While LFS may run in families, up to 25% of individuals with LFS may have acquired a faulty
TP53 gene at birth
(de novo). Therefore, genetic testing may also be offered in the absence of relevant family history and/or if an individual’s personal history is suspicious for LFS.
Personalised managementYour genetic test result may confirm whether your personal and/or family history is due to a hereditary condition like LFS, and clarify what your lifetime cancer risks may be. This information can be useful for doctors to personalise your medical care to help manage or reduce cancer risks.
If you have a cancer diagnosis
If you are currently cancer-free
Familial implicationsYour genetic test result can also help you understand if other family members are at risk of LFS. They can subsequently consider their own testing (predictive testing) to clarify their carrier status to determine tumour and cancer risks.Family members who
have inherited the same faulty
TP53 gene may be at increased risk of tumours and cancer and can benefit from management options such as screening (to detect tumours and cancer at an early and manageable stage) or surgery (to reduce their risk of cancer).Family members who
did not inherit the faulty
TP53 gene can avoid unnecessary screening and worry. Their children will also not be at risk.
Unnecessary radiation exposure for screening or therapeutic purposes should be avoided where possible.
Your managing doctor(s) will discuss screening recommendations with you in greater detail, which may be tailored based on your medical history. The age and onset of screening may depend on your personal and/or family history of the condition. Screening guidelines may change as more information is known.
In some cases, individuals can consider interventions such as surgery to reduce their risk of cancer.
This will be discussed in detail with you by your managing doctor(s). The surgery may reduce the risk of cancer significantly, but does not remove the risk completely.