Trial Information

Clinical, Epidemiologic, and Genetic Studies of Li-Fraumeni Syndrome

BACKGROUND:

- Li-Fraumeni syndrome (LFS) is a dominantly-inherited cancer predisposition syndrome
associated with a lifetime risk of approximately 90% by age 60 of numerous cancer
types, most notably bone and soft-tissue sarcomas, breast cancer, brain tumors,
leukemia, and adrenal cortical carcinoma

- Classic LFS is defined by 1) A proband with a sarcoma diagnosed before 45 years of age,
and 2) a first-degree relative with any cancer under 45 years of age, and 3) a first-
or second-degree relative with any cancer diagnosed under 45 years of age or a sarcoma
at any age. Li-Fraumeni-like syndrome (LFL), a more inclusive diagnostic criteria,
shares some of the features of LFS but that do not meet the strict LFS diagnostic
criteria

- TP53 was identified as the underlying cause of LFS in 1990. A TP53 mutation is
identified in approximately 70% of classic LFS and 40% of LFL

- Although screening LFS patients for certain cancers can lead to early detection, a
favorable impact on quality of life or overall survival as a result of such screening
has not been shown. Currently, there is no standard recommended screening protocol in
either adults or children with LFS

OBJECTIVES:

- To evaluate and define the clinical spectrum and quantify cumulative cancer risk in
individuals with LFS and LFL

- To develop a cancer screening program for individuals with LFS and LFL

- To identify genetic determinants, environmental factors, and gene-environment
interactions that potentially modify cancer risk in these high-risk individuals

- To explore the plausibility of lifestyle risk-reducing interventions

- Evaluate the psychological and social functioning effects of LFS on the individuals and
the family

- To create an annotated biospecimen repository of LFS-related materials for
translational

Research

ELIGIBILITY:

- A family or personal medical history of cancers consistent with the diagnosis of LFS or
LFL; or,

- A personal history of a germline TP53 mutation; or,

- A first- or second- degree relative of a TP53 mutation carrier, regardless of mutation
status; or,

- A personal history of three or more LFS-related primary cancers; or,

- A personal history of adrenal cortical carcinoma or choroid plexus carcinoma at any age

DESIGN:

- Long-term prospective cohort study to collect data from as many individuals with LFS as
permissible in order to precisely evaluate the main aims

- Medical/pathology records are reviewed to ascertain the family history and verify a
diagnosis of LFS. Questionnaires are administered to gather etiologic risk factor data.

- Participants are offered the option of undergoing a screening protocol and are followed
prospectively. Biospecimens are collected to investigate cancer etiology and mechanisms
of carcinogenesis.

- Clinical genetic testing is offered as appropriate after education and counseling.
Genetic testing is optional, and not required for other protocol aspects.

- We do not offer anti-cancer therapy; consultations for treatment recommendations of
cancer diagnosed while on study will be offered if available.