The TP53 gene is associated with Li-Fraumeni syndrome (LFS), a hereditary cancer predisposition characterized by very high lifetime risks for a wide range of early-onset cancers, most commonly sarcomas, breast cancer, brain tumors, adrenocortical carcinoma, and leukemias. Because TP53 plays a central role in DNA damage response, individuals with LFS require comprehensive management, including tumor surveillance starting in infancy, annual whole-body and brain MRI, and risk-reduction strategies such as early breast cancer screening or prophylactic surgery. TP53 pathogenic variants are not known to be more common in the Ashkenazi Jewish population.
Pathogenic variants in TP53 exhibit autosomal dominant inheritance. This means there is a 50% chance the condition can be passed from generation-to-generation. First degree relatives (parents, siblings, children) have a 50% chance to have the same pathogenic variant whereas second degree relatives (grandparents, aunts/uncles, nieces/nephews, half-siblings) have a 25% chance. More distant relatives have lower chances of having the same pathogenic variant when one is identified in the family.
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Written December 2025
