Etiologic Investigation of Cancer Susceptibility in
Inherited Bone Marrow Failure Syndromes (IBMFS)

Inherited bone marrow failure syndromes (IBMFS) are rare disorders in which there is usually some form of aplastic anemia (failure of the bone marrow to produce blood), associated with a family history of the same disorder. Some of these conditions have typical changes in physical appearance or in laboratory findings which suggest a specific diagnosis. There are several well-described syndromes, which can be recognized by health care experts. There are also patients who are harder to classify, but who appear to belong in this category.

Patients with these syndromes have a very high risk of development of cancer (either leukemia or certain solid tumors). At the moment we cannot predict which specific patient with an IBMFS is going to develop cancer. The NCI IBMFS Cohort Study will enroll North American families in which at least one member has or had an IBMFS. We plan to:

• include individuals known to have an IBMFS as well as their first degree relatives (brothers, sisters, parents, and children);
• collect clinical information from study participants and their physicians;
  
• perform detailed physical examinations, x-rays and routine laboratory tests on those who are interested in traveling to the NIH to be seen in person by our team;
  
• attempt (on a research basis) identification of the specific genetic mutation that is associated with each family's disease;
  
• screen participants for early changes related to the specific cancers that occur in each syndrome;
  
• perform detailed research laboratory studies on blood and tumors collected from study participants, in an effort to understand the process by which cancers develop;
  
• monitor study participants in an ongoing fashion to determine the rate at which complications develop related to each disease, and to identify those complications more precisely;
  
• provide suggestions to study participants and their physicians regarding how to best take care of family members who are affected with a particular IBMFS; and
  
• offer genetic counseling, and an opportunity to learn the results of mutation testing, for those persons who decide that this information will be of use to them.

The Principal Investigator responsible for this study is Blanche P. Alter, MD, MPH. For further information regarding her credentials and experience, please see: http://dceg.cancer.gov/people/AlterBlanche.html.

Our overall goal is to reach a better understanding of how cancers develop in persons with IBMFS, so that we may improve the health care which can be offered to persons with these disorders.