Clinical and Genetic Studies of Li-Fraumeni Syndrome

NCT01443468 | Recruiting

• 2 other identifiers: 11025511-C-0255
• Study Type: observational
• Target: 5,000
• Locations: 1 country
• Sites: 2

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.

Conditions

Li-Fraumeni Syndrome; Neoplasms; Tp53 Mutations

Keywords

Tp53; Cancer; Hereditary; Genetic Testing; Screening

Outcome Measures

Primary Outcomes (8)

• Prevalence

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

  ongoing

• Multiple measures

  Explore ways to lower cancer risk

  ongoing

• Multiple measures

  Explore the typical features of the cancers diagnosed in individuals with LFS

  ongoing

• Multiple measures

  Explore the psychological and social functioning issues faced by LFS families

  ongoing

• Multiple measures

  Explore the best ways to look for cancers early in individuals with LFS

  ongoing

• Multiple measures

  Determine if there is any connection between specific mutations in the TP53 gene and the risk of certain type of cancers

  ongoing

• Multiple measures

  Determine if there are any environmental factors or other genes that can change a person's cancer risk associated with LFS

  ongoing

• Multiple measures

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

  ongoing

Study Arms (5)

1

Patients within a family with a known TP53 mutation who are positive for that mutation.

2

Patients within a family with a known TP53 mutation who are negative for that mutation.

3

Unaffected family members.

4

Patients who meet clinical LFS criteria but haven't had TP53 testing.

5

Patients within a family with an negative/unknown TP53 mutation.

Eligibility Criteria

• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Eligibility for the LFS study population: - 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

You may qualify if:

• because of either:
• A family or personal medical history of neoplasia 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, regardless of family history
• Personal and family medical history must be verified through questionnaires, interviews, review
• of medical records and/or review of pathology slides.
• There are 72 families who have previously enrolled in the pilot study under protocol 78-C-0039.
• As the eligibility criteria remain the same, these families will be eligible for this protocol and will be invited to sign the new consent.
• Ability of subject or Legally Authorized Representative (LAR) to understand and the willingness to sign a written informed consent document.
• For both the Field and Clinical Center Cohort, the PI will ensure that study investigators will
• identify an appropriate LAR consistent with requirements of Policy 403 and will obtain consent
• from the LAR as outlined in the consent process before initiating research interventions.
• Pregnant women

You may not qualify if:

• Referred individuals and families whose reported diagnoses cannot be verified
• Medical or psychiatric disorder which, in the opinion of the Principal Investigator, would preclude the ability to participate in clinical research
• Women who are pregnant will not be eligible for the cancer screening protocol until they recover post-partum. Women participating in the cancer screening protocol will discontinue this component if they become pregnant while on study. Once they recover post-partum, they can continue the cancer screening protocol.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (2)

National Cancer Institute - Shady Grove

Bethesda, Maryland, 20892, United States

RECRUITING

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Publications (7)

• Mai PL, Malkin D, Garber JE, Schiffman JD, Weitzel JN, Strong LC, Wyss O, Locke L, Means V, Achatz MI, Hainaut P, Frebourg T, Evans DG, Bleiker E, Patenaude A, Schneider K, Wilfond B, Peters JA, Hwang PM, Ford J, Tabori U, Ognjanovic S, Dennis PA, Wentzensen IM, Greene MH, Fraumeni JF Jr, Savage SA. Li-Fraumeni syndrome: report of a clinical research workshop and creation of a research consortium. Cancer Genet. 2012 Oct;205(10):479-87. doi: 10.1016/j.cancergen.2012.06.008. Epub 2012 Aug 29.

  PMID: 22939227 BACKGROUND

• Villani A, Tabori U, Schiffman J, Shlien A, Beyene J, Druker H, Novokmet A, Finlay J, Malkin D. Biochemical and imaging surveillance in germline TP53 mutation carriers with Li-Fraumeni syndrome: a prospective observational study. Lancet Oncol. 2011 Jun;12(6):559-67. doi: 10.1016/S1470-2045(11)70119-X. Epub 2011 May 19.

  PMID: 21601526 BACKGROUND

• Malkin D. Li-fraumeni syndrome. Genes Cancer. 2011 Apr;2(4):475-84. doi: 10.1177/1947601911413466.

  PMID: 21779515 BACKGROUND

• Rising CJ, Huelsnitz CO, Shepherd RF, Klein WMP, Sleight AG, Wilsnack C, Boyd P, Feldman AE, Khincha PP, Werner-Lin A. Diet and physical activity behaviors: how are they related to illness perceptions, coping, and health-related quality of life in young people with hereditary cancer syndromes? J Behav Med. 2024 Aug;47(4):707-720. doi: 10.1007/s10865-024-00489-z. Epub 2024 Apr 20.

  PMID: 38642305 DERIVED

• Rising CJ, Wilsnack C, Boyd P, Sleight AG, Hutson SP, Khincha PP, Werner-Lin A. Family communication challenges of adolescents and young adults with Li-Fraumeni syndrome: Implications for psychosocial care. Patient Educ Couns. 2022 Nov;105(11):3259-3266. doi: 10.1016/j.pec.2022.07.012. Epub 2022 Jul 20.

  PMID: 35918231 DERIVED

• Werner-Lin A, Forbes Shepherd R, Young JL, Wilsnack C, Merrill SL, Greene MH, Khincha PP. Embodied risk for families with Li-Fraumeni syndrome: Like electricity through my body. Soc Sci Med. 2022 May;301:114905. doi: 10.1016/j.socscimed.2022.114905. Epub 2022 Mar 17.

  PMID: 35367908 DERIVED

• de Andrade KC, Khincha PP, Hatton JN, Frone MN, Wegman-Ostrosky T, Mai PL, Best AF, Savage SA. Cancer incidence, patterns, and genotype-phenotype associations in individuals with pathogenic or likely pathogenic germline TP53 variants: an observational cohort study. Lancet Oncol. 2021 Dec;22(12):1787-1798. doi: 10.1016/S1470-2045(21)00580-5. Epub 2021 Nov 12.

  PMID: 34780712 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Li-Fraumeni Syndrome; Neoplasms

Condition Hierarchy (Ancestors)

Neoplastic Syndromes, Hereditary; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; DNA Repair-Deficiency Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Payal P Khincha, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

NCI Family Study Referrals

CONTACT

(800) 518-8474; ncifamilystudyreferrals@mail.nih.gov

Payal P Khincha, M.D.

CONTACT

(240) 276-7267; payal.khincha@nih.gov

Study Design

• Study Type: observational
• Observational Model: FAMILY BASED
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 28, 2011
• First Posted: September 29, 2011
• Study Start: January 17, 2012
• Last Updated: June 11, 2026

Record last verified: 2026-06-09

Locations

US (2)