Individuals with Li-Fraumeni syndrome (LFS) have increased risk of developing several cancers as children, young adults, and throughout life due to an inherited mutation in the TP53 gene. With the increased use of panel testing for patients at high risk of inheritable cancer syndromes, more individuals are seeking to understand their LFS cancer risks during genetic counseling sessions. Current surveillance recommendations for LFS consists of a rigorous regiment of multiple preventative screenings performed every six months to one year. Our objective is to improve the clinical management of individuals with a family history of early-onset cancer by evaluating the performance of mathematical m...

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Individuals with Li-Fraumeni syndrome (LFS) have increased risk of developing several cancers as children, young adults, and throughout life due to an inherited mutation in the TP53 gene. With the increased use of panel testing for patients at high risk of inheritable cancer syndromes, more individuals are seeking to understand their LFS cancer risks during genetic counseling sessions. Current surveillance recommendations for LFS consists of a rigorous regiment of multiple preventative screenings performed every six months to one year. Our objective is to improve the clinical management of individuals with a family history of early-onset cancer by evaluating the performance of mathematical model-based clinical tools to assess the carrier probability of TP53 mutations and absolute lifetime risk of developing cancers in individuals with TP53 mutations. The rationale is that our advanced models will enable the systematic and comprehensive risk evaluation of patients and families with inherited TP53 mutations so that genetic counselors and physicians can provide more effective counseling and screening of LFS individuals, given the high frequency and varied cancer-type outcomes in these patients. Our significant contribution is to create an advanced clinical risk assessment tool that will more accurately quantify each individual's future cancer risk over his/her lifetime. Our advanced models are included in the software suite LFSPRO, which will be provided through a user-friendly web interface at cancer genetic clinics. This may bring LFS counseling to a new population and clinical setting to reach more families affected by TP53 mutations. The expected outcome of this research is to substantially improve the early detection of multiple cancer types in genetics clinics and to provide a general study design framework for the clinical dissemination of risk prediction software tools in multiple inherited cancer syndromes and cancer genes in the future.

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