TP53 Gene Mutations

Li-Fraumeni Syndrome (LFS)

TP53 Associated Cancer Risks

What does it mean to have a TP53 gene mutation, and a diagnosis of Li-Fraumeni Syndrome (LFS)?

People with mutations in the TP53 gene have a condition called Li-Fraumeni Syndrome, or LFS. People with LFS have a high risk for many different types of cancer. These cancers can develop at young ages, including childhood. TP53 mutations are often found in women who have developed breast cancer under age 30. Many people with LFS will be diagnosed with cancer 2 or more times during their lifetime.

Many of the cancers that are seen in people affected by LFS are quite rare for people who do not have LFS. Some of these cancers include: cancers of the adrenal gland, the choroid plexus (a part of the brain), and bone and muscle sarcomas. In addition to these unusual cancers, people with LFS have higher risks for more common cancers, like female breast cancer, colorectal cancer, and leukemia.

What can be done to protect people with LFS from cancer?

The National Comprehensive Cancer Network (NCCN) provides recommendations for lowering the risk of cancer in men and women with LFS. These recommendations include starting screening at younger ages and having screenings more often. For example, colonoscopies to check for colon cancer should begin at age 25 or younger, and should be done every 2 to 5 years. Women with LFS should begin breast screening in their 20’s, and should have MRIs instead of, or in addition to, mammograms. The risk of breast cancer in women with LFS is very high, and in some cases it may even be reasonable to consider surgery to remove the breasts before cancer can develop.

As mentioned earlier, people with LFS have a high risk for many different types of cancer, even in childhood. Some of these cancers are hard to detect. Research is now being done to develop ways to find these cancers as early as possible, when treatment is most likely to be successful. Available results from these studies have been encouraging. For more information about research studies, talk to your provider.

The gene that is altered in people with LFS, the TP53 gene, helps to repair DNA damaged by radiation. People with defects in the TP53 gene are more sensitive to radiation. Therefore, people with LFS should avoid exposure to radiation except when absolutely necessary.

Because LFS is associated with many different cancer risks, it is recommended that people with mutations in the TP53 gene be cared for by healthcare professionals with experience in treating this condition. A list of centers that have specialized knowledge and experience with LFS is available within our Support Organizations pages.

Additional details about TP53 gene mutations and LFS, including information about the risks for different kinds of cancer, specific recommendations for medical care, and useful information for relatives of people who have a diagnosis of LFS, are available within our Support Organizations page

TP53 gene

Associated Syndrome Name: Li-Fraumeni Syndrome (LFS)

Important Note: The information below applies only to individuals known to have TP53 mutations that are germline in nature (mutations present in all cells of the body). Some TP53 mutations which appear to be germline in nature are actually somatic mutations present in only a subset of blood cells or tissues, or in tumor cells contaminating the sample used for genetic testing. Individuals with somatic TP53 mutations do not have Li-Fraumeni Syndrome, and the information below regarding cancer risks, medical management options and information for family members may not apply.

TP53 Summary Cancer Risk Table

Cancer Genetic Cancer Risk
Female BreastHigh Risk
ColorectalElevated Risk
EndometrialElevated Risk
MelanomaElevated Risk
PancreaticElevated Risk
GastricElevated Risk
OvarianElevated Risk
ProstateElevated Risk
OtherHigh Risk

TP53 gene Overview

Li-Fraumeni Syndrome (LFS) 1, 2
  • Individuals with germline mutations in TP53 have a condition called Li-Fraumeni Syndrome (LFS).
  • Individuals with LFS have a high lifetime cumulative risk for a wide spectrum of cancers and for developing multiple primary tumors. Cancer risk is heavily biased towards younger ages, and individuals with LFS often develop cancer at early ages, with the majority of cancers diagnosed under age 45.
  • The most common cancers diagnosed in patients with LFS are premenopausal female breast cancer, soft tissue and bone sarcomas, adrenocortical carcinoma and brain tumors. However, the risk for a diverse group of other cancers is also thought to be increased as detailed in the Cancer Risk Table below.
  • The overall lifetime cancer risk for women is higher than that for men. This is mostly due to the very high risk for female breast cancer compared with the 12.5% lifetime risk for breast cancer in women in the general population of the United States. Male breast cancer risk is not thought to be increased.
  • When possible, individuals with LFS are advised to avoid therapeutic radiation therapy for the treatment of cancer, as this can increase the likelihood of additional malignancies.
  • Although the risk for cancer in patients with LFS is very high, it may be possible to reduce this risk with appropriate medical management. Guidelines for the management of patients with LFS have been developed by the National Comprehensive Cancer Network (NCCN). These are listed below. Since LFS is a rare and complex condition, it is recommended that patients with TP53 mutations and a diagnosis of LFS be managed by a multidisciplinary team with experience in the prevention and treatment of the many malignancies for which these patients are at risk.

TP53 gene Cancer Risk Table

Cancer Type Age Range Cancer Risk Risk for General Population *
Overall cancer risk (male and female)To age 53Up to 22%0.1%
Risk for a second primary cancer of any type after a first cancer diagnosis6Up to 57%NA
Overall cancer risk (female)To age 455Up to 84%3.5%
To age 855Up to 100%33.3%
Overall cancer risk (male)To age 455Up to 41%2.2%
To age 855Up to 73%40.4%
Female BreastTo age 801, 2Greatly increased risk, with a strong tendency towards very young ages of diagnosis - the large majority of cases occurring before menopause.10.2%
Other - including Adrenocortical Carcinoma, Choroid Plexus Carcinoma, Soft Tissue Sarcoma, Bone Sarcoma, and BrainTo age 801, 2, 3, 5Greatly increased risk, with a strong tendency towards young ages of diagnosis - sometimes in childhood.NA
ColorectalTo age 801, 7Elevated risk, with a strong tendency towards young ages of diagnosis - the median age of diagnosis is estimated to be 41.3.4%
OvarianTo age 802Elevated risk, with a tendency towards young ages of diagnosis.1.1%
PancreaticTo age 802Elevated risk, with a tendency towards young ages of diagnosis.1%
ProstateTo age 802Elevated risk, with a tendency towards young ages of diagnosis.13.6%
EndometrialTo age 802Elevated risk, with a tendency towards young ages of diagnosis.2.3%
GastricTo age 802Elevated risk, with a tendency towards young ages of diagnosis.0.6%
MelanomaTo age 802Elevated risk, with a tendency towards young ages of diagnosis.1.6%
Other - including non-Melanoma Skin, Lung, Leukemia, Lymphoma, Esophageal, Neuroblastoma, Thyroid, and KidneyTo age 801, 2, 5Elevated risk, with a tendency towards young ages of diagnosis.NA

TP53 Cancer Risk Management Table

The overview of medical management options provided is a summary of professional society guidelines as of the last Myriad update shown on this page. The specific reference provided (e.g., NCCN guidelines) should be consulted for more details and up-to-date information before developing a treatment plan for a particular patient.

This overview is provided for informational purposes only and does not constitute a recommendation. While the medical society guidelines summarized herein provide important and useful information, medical management decisions for any particular patient should be made in consultation between that patient and his or her healthcare provider and may differ from society guidelines based on a complete understanding of the patient’s personal medical history, surgeries and other treatments.

Cancer Type Procedure Age to Begin Frequency
Female BreastBreast awareness - Women should be familiar with their breasts and promptly report changes to their healthcare provider. Periodic, consistent breast self-examination (BSE) may facilitate breast awareness.118 yearsNA
Clinical breast examination120 to 25 years, or at the age of the earliest diagnosis in the family if under age 20.Every 6 to 12 months
Breast MRI with contrast and/or Mammography1Age 20 for MRI (preferred) or mammography. Age 30 for both MRI and mammography.Annually
Consider risk-reducing mastectomy.1IndividualizedNA
Other including Adrenocortical Carcinoma, Sarcomas, Brain tumors, Leukemia, Lymphoma, and other cancers, especially those for which there is a past diagnosis in the family.Comprehensive physical and neurological examination, and consideration of organ-targeted surveillance based on individual family histories.1Childhood, individualized based on patient personal and family historyAnnually
Whole body MRI, including brain1IndividualizedAnnually
ColorectalConsider colonoscopy.125 years, or 5 years younger than the earliest colorectal cancer in the family, whichever comes firstEvery 2 to 5 years
Other including Gastric, Ovarian, Endometrial, Prostate and Pancreatic cancer.Comprehensive physical and neurological examination, and consideration of organ-targeted surveillance based on individual family histories.1Individualized based on patient personal and family historyAnnually
Whole body MRI, including brain1IndividualizedAnnually
MelanomaSkin examination1Childhood, individualized based on patient personal and family historyAnnually

Information for Family Members

The following information for Family Members will appear as part of the MMT for a patient found to have a mutation in the TP53 gene.

A major potential benefit of myRisk genetic testing for hereditary cancer risk is the opportunity to prevent cancer in relatives of patients in whom clinically significant mutations are identified. Healthcare providers have an important role in making sure that patients with clinically significant mutations are informed about the risks to relatives, and ways in which genetic testing can guide lifesaving interventions.

Approximately 7%-20% of individuals with LFS have not inherited the TP53 mutation from a parent. In these cases the mutation has developed spontaneously in that individual (a de novo mutation). Once this occurs, the children of that individual are each at 50% risk of inheriting the mutation.2

Since TP53 mutations carry a very high risk for cancer in young children, it is important that consideration be given to the possibility of genetic testing and screening at very young ages.


  1. Daly M et al. NCCN Clinical Practice Guidelines in Oncology®: Genetic/Familial High-Risk Assessment: Breast and Ovarian. V 1.2017. September 19. Available at
  2. Schneider K, et al. Li-Fraumeni Syndrome. 2013 Apr 11. In: Pagon RA, et al., editors. GeneReviews® [Internet]. Available from PMID: 20301488.
  3. Bougeard G, et al. Revisiting Li-Fraumeni Syndrome From TP53 Mutation Carriers. J Clin Oncol. 2015 33:2345-52. PMID: 26014290.
  4. Surveillance Research Program, National Cancer Institute SEER*Stat software ( V 8.0.1, Nov 19, 2012.
  5. Chompret A, et al. p53 germline mutations in childhood cancers and cancer risk for carrier individuals. Br J Cancer. 2000 82:1932-7. PMID: 10864200.
  6. Hisada M, et al. Multiple primary cancers in families with Li-Fraumeni syndrome. J Natl Cancer Inst. 1998 90:606-11. PMID: 9554443.
  7. Wong P, Vet al. Prevalence of early onset colorectal cancer in 397 patients with classic Li-Fraumeni syndrome. Gastroenterology. 2006 130:73-9. PMID: 16401470.
Last Updated on 01-Jun-2017