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Clinical and Genetic Studies of Li-Fraumeni Syndrome

Recruiting
Conditions
Li-Fraumeni Syndrome
Tp53 Mutations
Neoplasms
Registration Number
NCT01443468
Lead Sponsor
National Cancer Institute (NCI)
Brief Summary

Background:

- Li-Fraumeni syndrome (LFS) is a genetic condition that increases the risk for some types of cancer. LFS may lead to cancer of the bone or connective tissue, breast, and brain. It may also increase the risk for certain types of leukemia and other cancers. The only known cause of LFS is a change (called a mutation ) in a gene known as TP53. However, not all people with LFS have a TP53 mutation. Researchers want to study other possible genetic causes of LFS, and factors that may increase or decrease cancer risk in people with the syndrome.

Objectives:

* To learn more about the types of cancers that occur in individuals with LFS.

* To study the role of the TP53 gene in the development of cancer.

* To look for other possible genes that cause LFS

* To study the effect of LFS diagnosis on families.

* To determine if environmental factors or other genes can change a person s cancer risk associated with LFS.

Eligibility:

* Individuals with a family or personal medical history of cancers consistent with LFS.

* Individuals with a family or personal medical history of cancers that does not meet the diagnosis of LFS, but the history is suggestive for LFS (meets the diagnosis for the so-called Li-Fraumeni like syndrome)

* Individuals with certain rare cancers

* Individuals with a family or personal history of a TP53 gene mutation, with or without related cancer(s).

Design:

* Participants will fill out a medical history questionnaire and a family history questionnaire.

* Blood samples will be collected for DNA and for storage. Cheek cell samples may be collected if blood cannot be obtained for DNA. Participants can choose to have or not have cancer screening with blood tests, imaging studies, and other exams.

* Participants will complete questionnaires about their worries about cancer, stress levels, and coping strategies. Diet and physical activity questionnaires will also be given. Other psychological tests may be given as needed.

* Participants will be monitored for several years, with regular followup visits to the National Institutes of Health, if indicated. Any changes in health or cancer status will be recorded.

Detailed Description

Study Description:

This is a natural history study involving questionnaires, clinical and research evaluations, clinical and research laboratory tests, review of

medical records, and cancer surveillance. This is a prospective long-term study of individuals at high risk of cancer due to Li-Fraumeni Syndrome (LFS) or Li-Fraumeni-Like Syndrome (LFL), using a cohort approach. Enrollees are invited to participate in all aspects of the study but can choose to opt out of specific part(s).

Objectives:

Primary Objectives:

* To ascertain/enroll individuals and families with Li-Fraumeni Syndrome (LFS) and Li-Fraumeni-Like Syndrome (LFL)

* To evaluation and define the clinical spectrum and natural history of disease in LFS and LFL

* To quantify cumulative cancer risk in individuals with LFS or LFL

* To develop a cancer screening program for individuals with LFS or LFL

* To investigate the mechanisms of tumorigenesis in LFS-related tumors (e.g., cell proliferation, growth regulation, apoptosis)

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

these high-risk individuals

* To evaluate the psychological, behavioral, and social functioning effects of LFS on affected individuals and their family members

* To explore the plausibility of lifestyle interventions as potential strategies for cancer risk reduction

* To create an annotated biospecimen repository of LFS-related for translational, etiologic, and outcomes research

Secondary Objectives:

-To evaluate specific tumor characteristics, including histologies (e.g., leukemia types, brain tumor types, etc.) of cancers

diagnosed in individuals with LFS or LFL.

-To evaluate the potential effect of therapeutic radiation and radiation exposure from diagnostic/screening imaging studies on

cancer risk.

* To provide education, cancer risk assessment, and risk management recommendations for study participants.

* To collect clinical data related to the treatment of LFS-related cancers, so that outcome and survival may be evaluated.

Endpoints: Primary Endpoint:

-Occurrence of cancer in individuals and families with LFS or LFL

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
5000
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Multiple measuresongoing

Determine how often a change (mutation) in the TP53 gene is found in families in which LFS is suspected

Prevalenceongoing

Learn more about the types of cancers that occur in individuals with LFS and the age at which these cancers are usually found

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (2)

National Cancer Institute - Shady Grove

🇺🇸

Bethesda, Maryland, United States

National Institutes of Health Clinical Center

🇺🇸

Bethesda, Maryland, United States

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