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).
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.
Study Type
OBSERVATIONAL
Enrollment
1,500
* 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).
Boston Children's Hospital
Boston, Massachusetts, United States
RECRUITINGBrigham and Women's Hospital
Boston, Massachusetts, United States
RECRUITINGJudy E. Garber
Boston, Massachusetts, United States
RECRUITINGRepository of specimens and data
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.
Time frame: 5 years or Study closure
Estimation of Cancer Risks in TP53 mutation carriers
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.
Time frame: 5 years or Study closure
Modified segregation analysis
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
Time frame: 5 years or Study closure
Estimation of risk for the more commonly occurring cancers associated with inherited TP53 mutations
P-values and 95% confidence intervals will be calculated
Time frame: 5 years or Study closure
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