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Cancer Genetics

Li-Fraumeni Syndrome



If p53 is the most common gene for a cancer mutation, why is Li-Fruameni syndrome considered so rare? It`s involved in 50% of cancers, right?

Wouldn`t radiation treatment for embryonal rhabdomyosarcoma (soft palate) create a likely "environment" for a later breast cancer?


ANSWER #1: Li-Fraumeni syndrome is thought to occur between 1 in 300,000 to 500,000 people. It is very rare when you consider that the p53 gene functions abnormally in at least half of all cancers in the body. There is a logical explanation, however.

Genes come in pairs. In each cell of the body, there are usually two working copies of the p53 gene. These genes are responsible for helping to control normal cell death ("apoptosis"). If the p53 genes do not work properly, the cell fails to die which helps lead to cancer.

Over time (months to years), one of the p53 gene copies in one cell may get damaged. The cell still works normally because the other gene copy is present. As more time passes, the other gene copy may also become damaged. Then the cell is able to grow and multiply without proper control. This is called a "somatic" mutation of p53.

People with Li-Fraumeni syndrome are born with one of the p53 gene copies not working properly because of an inherited change in the gene. Instead of one cell in the body with a defective p53 gene, every cell in the body has a defective gene. If any other cell develops a problem with the second p53 gene copy, cancer may develop. Because a person is born with the gene change, this is called a "germline" mutation.

This explanation fits what we know about Li-Fraumeni syndrome (LFS). People with LFS tend to get cancer at a very early age. All sorts of cancers may occur in the family including colon cancer, lung cancer, ovarian cancer, breast cancer, leukemia, lymphoma, brain cancer, sarcomas, and adrenal gland tumors.

ANSWER #2: Radiation treatment for any kind of cancer always increases the long term risk for the development of other kinds of cancer within the field of the radiation. If a person had radiation treatment of the soft palate, they may or may not have an increased risk for breast cancer depending on how well-focussed the radiation beam was on the soft palate. Radiation oncologists work very carefully to minimize the radiation beam to avoid damaging other areas of the body.

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Response by:

Judith A Westman, MD Judith A Westman, MD
Associate Professor, Clinical Internal Medicine, Pediatrics and Medical Biochemistry
College of Medicine
The Ohio State University