Clinical and Genetic Studies of Li-Fraumeni Syndrome

Summary

Participation Requirements

Description

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 C...

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.

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