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NCT Number: NCT04541654

Li-Fraumeni & TP53 (LiFT UP): Understanding and Progress

The purpose of this research study is to learn more about variants in the TP53 gene both associated with Li-Fraumeni Syndrome (LFS), a hereditary cancer risk condition, and TP53 variants found in the blood for other reasons (e.g. ACE/CHIP and mosaicism).

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Key information

Conditions

Li-Fraumeni Syndrome Clonal Hematopoiesis Congenital, Hereditary, and Neonatal Diseases and Abnormalities DNA Repair-Deficiency Disorders Genetic Diseases, Inborn Hereditary Cancer Syndrome Metabolic Diseases Mosaicism Neoplasms Neoplastic Syndromes, Hereditary Nutritional and Metabolic Diseases TP53 Gene Mutation

Sex eligibility

All sexes

Study type

Observational

Primary location

Boston Children's Hospital, Boston, Massachusetts, United States

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About this study

This research study looks to enroll as many people with LFS or TP53 gene variants as possible in order to:

  • Better estimate cancer risks in individuals with TP53 variants or LFS, which is a rare condition.
  • Learn the range of cancer risks linked to TP53 variants to help individuals and families to improve our ability to counsel patients and families about cancer risks more accurately.
  • Improve opportunities for cancer prevention, early detection, and treatment.
  • Learn more about the meaning of TP53 variants in the blood that are not inherited (e.g. ACE/CHIP and mosaicism).

Study procedures will include:

  • Collecting information from the participant's medical record and short questionnaires.
  • Collecting blood, saliva, eyebrow hair and tumor tissue samples (optional).
  • Sharing study information with family members (optional).

It is expected that about 1500 people will take part in this research study. Participants will be in this study until it closes or the participant withdraws consent.

The National Cancer Institute is providing funding for part of this study and is considered a study sponsor. They will require that some of the genetic information be made available to the research community without personal identifying information.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Individuals with a TP53 pathogenic or likely pathogenic variant identified in blood or saliva,
  • Individuals with variants of uncertain significance in TP53 may be eligible at the PI's discretion,
  • Blood relatives of individuals with a TP53 variant, who may be presumed obligate carriers or healthy controls,
  • Individuals who meet Classic or Chompret LFS criteria whether or not they have a TP53 gene variant,
  • Individuals may enroll their deceased relatives in the study.
  • Individuals with a known TP53 variant that is not LFS, but rather ACE, CHIP, or mosaicism.
  • Individuals participating in other LFS studies can still enroll in LiFT UP. Investigators may be collaborators.

Exclusion criteria

  • Individuals who decline to sign consent
  • Individuals who are unable to give consent or assent and are without a designated healthcare proxy

Treatment and study plan

Data and Specimen Collection

Genetic
  • Provide research team and access to relevant medical records
  • Answer short questionnaires periodically
  • Consider consenting to other optional parts of the research such as:
  • Providing up to 3 tubes (15ml) of blood at or near the time of consent, as approved by treating physician (optional).
  • Provide a saliva sample (optional).
  • Provide eyebrow hairs for analysis of DNA from the bulb (15-20 eyebrow plucks) (optional).
  • Provide permission for obtainment of stored tissue specimens from cancer or pre-cancer surgeries or biopsies from the pathology departments where they have been stored (optional).
  • Consider inviting relatives to join the study (optional).

Primary outcomes

  1. Repository of specimens and data

    Time frame: 5 years or Study closure

    Examine accuracy of family history and the extent to which families meet various published Li-Fraumeni family criteria or assess for de-novo mutations using descriptive statistics. Exact binomial confidence limits for percents will be calculated at 95% coverage. Tests of difference between >2 groups for binary variables will use the Fisher exact test.

Secondary outcomes

  1. Estimation of Cancer Risks in TP53 mutation carriers

    Time frame: 5 years or Study closure

    Estimate the frequency in ExAc as a population rate and calculate a standardized risk ratio as the ratio of the prevalence of mutations in a given cancer type compared to that in ExAc. P-values and 95% confidence intervals will be calculated assuming the observed number of mutations follows a Poisson distribution with mean equal to the expected value calculated from the ExAC observed frequency.

  2. Modified segregation analysis

    Time frame: 5 years or Study closure

    For each dataset, the following analyses will be performed using MENDEL: a) the relative risk (RR) across age groups is assumed to be constant; b) the RR is assumed to be a continuous, piece wise linear function of age which was constant before age 40 years and after age 60 years, and linear between ages 40 and 60 years

  3. Estimation of risk for the more commonly occurring cancers associated with inherited TP53 mutations

    Time frame: 5 years or Study closure

    P-values and 95% confidence intervals will be calculated

Study contacts

Contact information is provided by the study sponsor or research team.

Judy E Garber, MD, MPH

CONTACT

[email protected]

617-632-5770

Sophie Cahill, BS

CONTACT

[email protected]

617-632-4795

Sponsors and collaborators

Lead sponsor

Dana-Farber Cancer Institute

Other

Collaborators

  • Baylor College of Medicine
  • City of Hope Medical Center
  • National Cancer Institute (NCI)

Registry information

Official study title

Li-Fraumeni & TP53: Understanding and Progress (LiFT UP)

Acronym: LiFT_UP

Important dates

Study start
2020
Primary completion
2030
Study completion
2032
First posted
Sep 9, 2020
Registry last updated
Mar 27, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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