Gene guide
TP53 gene: p53, the "guardian of the genome"
TP53 makes p53, a protein that stops damaged cells from dividing. It is the most frequently mutated gene in human cancers. Inherited harmful TP53 variants are rare and cause Li-Fraumeni syndrome, a strong predisposition to several cancers from childhood onward.
- Full name
- Tumor protein p53
- Chromosome
- 17 (17p13.1)
- Role
- Tumor suppressor: senses DNA damage and pauses the cell cycle, starts DNA repair, or triggers cell death
- Inherited condition
- Li-Fraumeni syndrome (autosomal dominant)
- Somatic role
- Acquired TP53 mutations are found in many cancers, including ovarian, colorectal, lung and head and neck
What does p53 do?
p53 is a transcription factor: it switches other genes on and off. Normally it is kept at low levels. When a cell's DNA is damaged, or the cell is under other stress such as a cancer-promoting signal, p53 is stabilized and activates genes that halt the cell cycle so the damage can be repaired. If the damage is too great, p53 pushes the cell into apoptosis (programmed cell death) or permanent arrest. This is why p53 is often called the "guardian of the genome".
When both copies of TP53 are inactivated in a cell, that safety check is lost and damaged cells can keep dividing. TP53 is mutated in a large share of human cancers, and the type and position of the mutation are increasingly used in diagnosis, prognosis and treatment decisions (Olivier 2010).
Li-Fraumeni syndrome
In 1990, researchers found inherited TP53 mutations in all five Li-Fraumeni families they studied (Malkin 1990). People who inherit one harmful TP53 variant have a very high lifetime risk of cancer, often at young ages. Typical cancers include breast cancer, soft-tissue and bone sarcomas, brain tumors, adrenocortical carcinoma and leukemia.
The condition is autosomal dominant: each child of a carrier has a 50% chance of inheriting the variant. Some cases arise from a new (de novo) variant with no family history. People with Li-Fraumeni syndrome can benefit from intensive surveillance, often including yearly whole-body MRI, under the care of a specialist team (see the GeneReviews summary below).
When to think about TP53 testing
Clinical guidelines suggest TP53 testing for people with, for example, a sarcoma, brain tumor or breast cancer before age 46 together with a close relative with one of these cancers, a person with several primary cancers, or anyone with adrenocortical carcinoma or certain other childhood cancers. A genetic counselor can tell you whether you meet the criteria and arrange clinical-grade testing.
Can raw DNA data detect harmful TP53 variants?
Not reliably. Consumer DNA chips are very accurate for common variants but much less so for very rare ones, which is what disease-causing TP53 variants are. In UK Biobank, only 16% of very rare variants called by SNP chips were confirmed by sequencing (Weedon 2021). A clinical laboratory found that 40% of variants reported in consumer raw data and sent for confirmation were false positives (Tandy-Connor 2018).
So a TP53 finding in raw data should be treated as a reason to see a genetic counselor and get clinical confirmation, never as a diagnosis. Equally, a "normal" chip result does not rule out Li-Fraumeni syndrome. Whole genome sequencing reads the whole TP53 gene and is much more reliable.
Lifestyle and p53
No diet or supplement can repair an inherited TP53 variant. For carriers, medical advice usually includes avoiding unnecessary radiation such as CT scans when possible (because cells with a TP53 variant are more sensitive to radiation-induced cancer), not smoking, limiting sun exposure and alcohol, and keeping up with recommended screening.
NutraHacker reports that include TP53
Every raw DNA upload also gets a free Detoxification and Methylation Report, genome imputation and a Superhuman traits report. See what you can do with raw DNA data.
Related reading
- MUTYH, a DNA repair gene and inherited polyposis
- A BRCA1 variant explained
- Glossary: autosomal dominant
- Glossary: genetic counselor
- Glossary: whole genome sequencing
Frequently asked questions
What does the TP53 gene do?
It makes p53, a tumor suppressor protein that detects DNA damage and stops damaged cells from dividing, repairs the damage or triggers cell death.
What is Li-Fraumeni syndrome?
An inherited condition caused by a harmful TP53 variant. It carries a very high lifetime risk of cancers such as breast cancer, sarcomas, brain tumors and adrenocortical carcinoma, often at young ages.
Is a TP53 mutation in a tumor the same as an inherited one?
No. Most TP53 mutations are acquired in tumor cells during life and are not passed on. Inherited (germline) variants are present in every cell and are rare.
Can 23andMe raw data show a TP53 mutation?
Chip data is unreliable for rare variants like those that cause Li-Fraumeni syndrome. Any finding needs clinical confirmation, and a normal result does not rule it out.
Who should get TP53 testing?
People with certain cancers at a young age, several primary cancers, or a family history that fits Li-Fraumeni syndrome. A genetic counselor can check the criteria.
References
- Malkin D, et al. Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms. Science. 1990;250(4985):1233-8. PubMed 1978757
- Olivier M, et al. TP53 mutations in human cancers: origins, consequences, and clinical use. Cold Spring Harb Perspect Biol. 2010;2(1):a001008. PubMed 20182602
- Li-Fraumeni Syndrome. In: GeneReviews. University of Washington, Seattle; 1993-. PubMed 20301488
- Weedon MN, et al. Use of SNP chips to detect rare pathogenic variants: retrospective, population based diagnostic evaluation. BMJ. 2021;372:n214. PubMed 33589468
- Tandy-Connor S, et al. False-positive results released by direct-to-consumer genetic tests highlight the importance of clinical confirmation testing for appropriate patient care. Genet Med. 2018;20(12):1515-1521. PubMed 29565420