The cumulative cancer risk in persons with TP53 mutations was very high overall, but varied by age, sex, and cancer type, a study published in the journal Cancer has shown.1

Carriers of a germline TP53 pathogenic variant have a substantial lifetime risk of developing cancer. Patients with a germline TP53 mutation are classified as having Li-Fraumeni syndrome, an autosomal dominant cancer predisposition syndrome also associated with early age at the time of cancer diagnosis.

Although previous research has demonstrated that Li-Fraumeni syndrome is associated with a very high lifetime cancer risk, precise estimates for the risk of first and subsequent cancers are unknown.

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For the study, researchers analyzed data from 286 TP53 mutation-positive patients from 107 families. Results showed that the cumulative cancer incidence was 50% by age 31 years among female family members and 46 years among males. The cumulative cancer incidence was nearly 100% by age 70 years for both sexes.

Researchers found that cancer risk was highest after age 20 years for female family members, while the risk was higher during childhood and late adulthood among male family members.

The study further revealed that among females, the cumulative incidence rates by age 70 years for breast cancer, soft tissue sarcoma, brain cancer, and osteosarcoma were 54%, 15%, 6%, and 5%, respectively. Among males, the incidence rates for soft tissue sarcoma, brain cancer, and osteosarcoma were 22%, 19%, and 11%, respectively.

Of note, nearly half of those with 1 cancer developed at least a subsequent cancer after a median of 10 years.

“Additional work, including prospective risk estimates, is needed to better inform personalized risk management,” the authors conclude.


1. Mai PL, Best AF, Peters JA, et al. Risks of first and subsequent cancers amongTP53 mutation carriers in the National Cancer Institute Li-Fraumeni syndrome cohort. Cancer. 2016 Aug 6. doi: 10.1002/cncr.30248.