Chordoma is a rare bone tumor that is diagnosed in only about 300 patients in the U.S. each year. It develops from cells located in the base of the skull, the vertebrae, and the sacrum or the coccyx (the tail bone). It occurs in these three regions with equal frequency. The cells that give rise to chordoma are left over from a structure called the notochord. The notochord is present in the embryo before birth but usually disappears almost entirely shortly after birth. The leftover notochord cells are called “notochord rests”.
Chordoma is diagnosed most often in people who are in their late 50s, but it can occur much earlier or later. It develops in males more often than females. For unknown reasons, it rarely occurs in African Americans. No specific environmental risk factors that increase the chance that a person will develop chordoma have been identified. The vast majority of people with chordoma have no other family member with this tumor. However, recent studies suggest that rare genetic or hereditary factors may increase the risk of relatives developing chordoma in some families.
Background
Since 1958, only 6 families with multiple relatives with chordoma have been reported in medical journals. In most of these families, chordoma occurred in a parent and one or more of his/her children. This pattern suggests that the tumor results from inheritance of an altered or mutated gene.
Recently, investigators in the Genetic Epidemiology Branch (GEB), National Cancer Institute (NCI), studied several families with multiple relatives with chordoma. The purpose was to try to identify the altered gene in these families that increased the risk of relatives developing chordoma. The studies included both clinical and laboratory components. In the clinical part, family members with chordoma as well as their unaffected blood relatives had imaging studies done; these took pictures of the bones at the base of the skull and along the spine. Through the imaging studies, we found very small chordomas in several of the relatives. The laboratory studies were done on DNA (the genetic material) obtained from blood from all of the family members. When we analyzed information from the clinical studies together with the results from the laboratory studies, we concluded that a mutated gene that increased the risk of developing chordoma was located on chromosome 7. Unfortunately, we did not have enough information to identify the altered gene.
Now our goals are to identify the "chordoma" gene and study it to learn how changes in it can lead to the development of chordoma. To reach these goals, we need to find and study more families in which two or more blood relatives have been diagnosed with chordoma.
Purpose of the Study
- Find the gene or genes that cause chordoma to occur in multiple relatives in a family;
- Describe the clinical findings in people with "familial" chordoma;
- Determine whether families prone to chordoma are at increased risk of other types of cancer; and
- Develop better health care choices for families who have an increased risk for developing chordoma.
Who are the Responsible Investigators?
The Study Team consists of the following researchers:
Dilys M. Parry, Ph.D. - She is a board certified Ph.D. medical geneticist who has been involved in research on familial and hereditary cancers for 27 years. She began studying chordoma families in 1996 and then initiated this study.
Mary L. McMaster, M.D. - She is a board certified internist and medical oncologist with specialty training in clinical genetics as well. Her main interest is studying cancer-prone families.
Deborah Zametkin, R.N., M.S.N. - She is a senior research nurse who has been working with patients with familial and hereditary cancers for 12 years. She has been involved in the Familial Chordoma Study since 1996.
Michael J. Kelley, M.D. - He is a board certified internist and medical oncologist. One of his research interests is identifying genes that change a person's risk of developing cancer. He directs the laboratory aspects of this study.
Alisa M. Goldstein, Ph.D. - She is a board certified Ph.D. medical geneticist. She is interested in identifying genes and environmental factors that increase a person's risk for developing cancer. She is responsible for analyzing the clinical and laboratory data from this study.
What Does Participation in the Study Involve?
Those who choose to participate in the Familial Chordoma Study will be asked to:
- Provide a blood sample or cells rinsed from inside of the mouth for genetic studies which may help us find the gene or genes that cause familial chordoma;
- Provide personal medical and family history information; and
- Give us permission to obtain past medical records about chordoma, other cancers and related illnesses, and a small piece of tumor stored after any cancer surgery.
In addition, some individuals may be invited to the Clinical Center of the National Institutes of Health (NIH) to participate in clinical and laboratory studies. The clinical part may include magnetic resonance (MR) imaging studies of the head and spine.
This study has been reviewed and approved by the Institutional Review Board (IRB) of the NCI. NCI is required by Federal law not to reveal any personal information that is collected from study participants to anyone other than persons directly involved with the study. A system is in place to ensure your privacy; in addition, all information obtained as part of this research is protected from disclosure by a Certificate of Confidentiality issued by the NCI.
Participants and family members will be able to ask questions and stay in touch with the research team. Participants will be asked to complete a yearly follow-up form to update medical information. We will provide participants with the overall findings of the study when analysis of information from the study is completed.
Costs: NCI will pay all study-related medical expenses and travel costs to the NIH Clinical Center for participants.
Treatment: Treatment is not offered as part of this study. However, if the need arises, we will discuss treatment options with participants. We will also provide assistance in establishing care with appropriate physicians as needed. Study participants will remain under the care of their primary doctors while participating in the study.
Who is Eligible to Participate in the Study?
To participate in the study, a family must have one of the following:
- Two or more blood relatives with a history of chordoma, or
- One blood relative with a history of chordoma and one or more blood relative(s) with a history of a brain tumor as a child or young adult.
The family members who are eligible to participate include those with chordoma or a brain tumor, their parents, siblings and children. We may also invite other blood relatives to join the study if they are genetically linked to family members with chordoma or have another form of cancer.
In addition, we may invite the spouse of a person with a history of chordoma or a childhood brain tumor who is enrolled in the study to participate if their children are enrolled in the study.
If your family fits one of the categories listed above and you and other family members are interested in contributing to research on familial chordoma, please complete and submit the Familial Chordoma study form. An investigator will get back to you in a few days.
While reasonably safe, e-mail is not perfectly secure. If you prefer, you can call toll-free 1-800-518-8474 and ask to speak with Ms. Stephanie Steinbart. She is one of our research nurses who knows about the Familial Chordoma Study. She can answer your questions and provide additional information about it. From Canada and Mexico, call collect to Ms. Steinbart at 301-881-1460.
