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Role of p53 Gene in Metabolism Regulation in Patients With Li-Fraumeni Syndrome

This study is currently recruiting participants.
Verified May 2013 by National Institutes of Health Clinical Center (CC)
Information provided by:
National Institutes of Health Clinical Center (CC) Identifier:
First received: November 25, 2006
Last updated: March 14, 2014
Last verified: May 2013

This study will examine metabolic and biological factors in people with Li-Fraumeni syndrome, a rare hereditary disorder that greatly increases a person's susceptibility to cancer. Patients have a mutation in the p53 tumor suppressor gene, which normally helps control cell growth. This gene may control metabolism as well as cancer susceptibility, and the study findings may help improve our understanding of not only cancer but also other conditions, such as cardiovascular function.

Healthy normal volunteers and patients with the Li-Fraumeni syndrome and their family members may be eligible for this study. Candidates must be at least 18 years of age, in overall good health and cancer-free within 1 year of entering the study. Participants undergo the following procedures:

"< TAB> Blood tests for routine lab values and for research purposes.

"< TAB> ECG and echocardiogram (heart ultrasound) to evaluate heart structure and function.

"< TAB> Resting and exercise metabolic stress testing: The subject first relaxes in a chair wearing the facemask and then exercises on a stationary bicycle or treadmill while wearing the mask. This test uses the facemask to measure oxygen usage by the body to determine metabolic fitness. Electrodes are placed on the body to monitor the heart in an identical manner to a standard exercise stress test.

"< TAB> Magnetic resonance imaging of metabolism: The subject lies on a bed that slides into a large magnet (the MRI scanner) for up to 60 minutes. During scanning, the arm or leg muscles are stressed by inflating a blood pressure cuff and by exercising the limb for several minutes. Subjects may be asked to squeeze a rubber ball or exercise with a foot pedal. Immediately afterwards, the pressure in the cuff is released and remains deflated for 10 to 15 minutes. No more than three 5-minute episodes of blood flow stoppage are performed.

"< TAB> Standard MRI scan of exercised limb to determine muscle volume.

"< TAB> Brachial artery reactivity test to measure blood vessel function: Before the exercise stress testing, subjects lie on a stretcher while the brachial artery (artery in the forearm) is imaged using a noninvasive ultrasound method. Artery size and blood flow velocity are measured before and after inflating a blood pressure cuff on the forearm. Vessel size and flow velocity measurements are repeated after 15 minutes and again after administration of nitroglycerin under the tongue.

"< TAB> Oral glucose tolerance testing to test for diabetes: To assess sugar metabolism, subjects drink a sugar solution. Blood samples are collected before drinking the solution and 1 and 2 hours after drinking the solution.

"< TAB> Muscle biopsy (optional according to subject preference): Subjects may be given small amounts of sedation for the procedure. A small area of skin over a leg muscle is numbed and a small amount of muscle tissue is surgically removed.

Li-Fraumeni Syndrome
Cardiovascular Capacity

Study Type: Observational
Study Design: Time Perspective: Prospective
Official Title: Metabolic Regulation by Tumor Suppressor p53 in Li-Fraumeni Syndrome

Resource links provided by NLM:

Further study details as provided by National Institutes of Health Clinical Center (CC):

Estimated Enrollment: 246
Study Start Date: November 2006
Detailed Description:

We have recently reported that TP53 (encoding p53 protein), one of the most frequently mutated genes in human cancers, dose dependently modulates the balance between the utilization of oxidative and glycolytic pathways for energy generation in human colon cancer cells and mouse liver mitochondria. Though morphologically similar to their wild-type littermates, mice deficient in p53 display a gene dose-dependent decrease in aerobic exercise capacity, implying that p53 has functions beyond its well characterized cell cycle activities. These current findings have broad implications in fields ranging from cancer and aging research to cardiovascular physiology.

In the Li-Fraumeni familial cancer syndrome (LFS), affected individuals harbor a germline mutation in TP53, hence they are heterozygous with reduced wild-type p53 activity. We hypothesize that the heterozygous individuals will display deficiency in aerobic capacity and metabolism that previously has been unappreciated. This IRB proposal translates our experimental observation to human subjects in collaboration with an extramural group studying this rare familial syndrome. The results may not only help clarify why mutations of p53 gene are so common in cancers by potentially conferring metabolic advantages in tumorigenesis, but they may also give us an opportunity to understand a fundamental regulatory mechanism in cellular energy generation relevant to other processes.


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes

    1. At least 18 years of age and able to give informed consent
    2. In overall good health;
    3. Able to exercise on a treadmill (if participating in the treadmill exercise portion).
    4. Able to perform hand or leg exercises (if participating in the MRS Portion)


  1. Blood pressure higher than 190/100 mmHg
  2. Diabetes requiring medical treatment
  3. Anemia
  4. Tobacco use within the past three months
  5. Symptomatic heart disease, heart failure or poor blood circulation
  6. Diseases predisposing to vasculitis or Raynaud's phenomenon
  7. Undergone stem cell transplantation
  8. Inflammatory disease or immunosuppressive therapy
  9. Claustrophobia and/or unable to lie on your back in the MRI machine
  10. Pregnant or breast feeding
  11. Body mass index under 19 or over 45
  12. Metal medical implantable device or other MRI incompatible materials

Additional Exclusion Criteria for the Muscle Biopsy:


  Contacts and Locations
Please refer to this study by its identifier: NCT00406445

Contact: Dorothy J Tripodi, R.N. (301) 496-3431
Contact: Paul M Hwang, M.D. (301) 435-3068

United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL)    800-411-1222 ext TTY8664111010   
Sponsors and Collaborators
Principal Investigator: Paul M Hwang, M.D. National Heart, Lung, and Blood Institute (NHLBI)
  More Information

Additional Information:
Additional publications automatically indexed to this study by Identifier (NCT Number): Identifier: NCT00406445     History of Changes
Other Study ID Numbers: 070030, 07-H-0030
Study First Received: November 25, 2006
Last Updated: March 14, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Oxygen Consumption
Aerobic Capacity
Magnetic Resonance Spectroscopy
Li-Fraumeni Syndrome

Additional relevant MeSH terms:
Li-Fraumeni Syndrome
Neoplastic Syndromes, Hereditary
Genetic Diseases, Inborn
DNA Repair-Deficiency Disorders
Metabolic Diseases processed this record on April 23, 2014