Clinical Trial: Clinical and Genetic Studies of Li-Fraumeni Syndrome

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational

Official Title: Clinical, Epidemiologic, and Genetic Studies of Li-Fraumeni Syndrome

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).

Detailed Summary:

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 e
    Sponsor: National Cancer Institute (NCI)

    Current Primary Outcome:

    • Learn more about the types of cancers that occur in individuals with LFS and the age at which these cancers are usually found [ Time Frame: Ongoing ]
    • Determine how often a change ( mutation ) in the TP53 gene is found in families in which LFS is suspected [ Time Frame: Ongoing ]
    • Determine if there is any connection between specific mutations in the TP53 gene and the risk of certain type of cancers [ Time Frame: Ongoing ]
    • Explore the typical features of the cancers diagnosed in individuals with LFS [ Time Frame: Ongoing ]
    • Explore the psychological and social functioning issues faced by LFS families [ Time Frame: Ongoing ]
    • Determine if there are any environmental factors or other genes that can change a persons cancer risk associated with LFS [ Time Frame: Ongoing ]
    • Explore the best ways to look for cancers early in individuals with LFS [ Time Frame: Ongoing ]
    • Explore ways to lower cancer risk [ Time Frame: Ongoing ]


    Original Primary Outcome:

    Current Secondary Outcome:

    Original Secondary Outcome:

    Information By: National Institutes of Health Clinical Center (CC)

    Dates:
    Date Received: September 28, 2011
    Date Started: September 6, 2011
    Date Completion:
    Last Updated: May 17, 2017
    Last Verified: January 5, 2017