Genetic Study of Cancer Risk and Gene Identification in Patients With Inherited Bone Marrow Disorders and Their Families

OBJECTIVES:

- Establish a cohort of North American families with Fanconi's anemia (FA) or other
inherited bone marrow failure syndromes (IBMFS) to determine the incident and prevalent
rates of cancer (for all cancer and each type of cancer) in patients with these
disorders.

- Determine the specific types of cancer associated with each type of IBMFS.

- Compare the biology of incident and prevalent tumors in IBMFS patients vs their
sporadic counterparts in the general population.

- Determine whether FA or other IBMFS gene products are involved in the cancer pathways
of the sporadic cancers seen in the general population that are common in patients with
IBMFS.

- Determine differences, including genotype, phenotype, cancer susceptibility
differences, modifier genes (gene-gene interactions), and environmental risk factors
(gene-environment interactions), between those patients with FA or IBMFS who develop
cancer and those with the same IBMFS who do not develop cancer.

- Determine the risk of cancer in individuals who are carriers of FA or other IBMFS gene
mutations.

- Compare cellular and molecular characteristics of tumor biopsies and specimens from
IBMFS patients vs cancers in the same tissues from the general population.

- Compare myelodysplastic syndromes (MDS) in these patients vs primary and secondary MDS
in the general adult and pediatric population.

- Examine germline and tumor specimen DNA for IBMFS mutations from individuals not
previously diagnosed with an IBMFS if they have tumors typical of IBMFS and do not have
the risk factors seen in the general population.

- Search for genes that might modify cancer susceptibility in these patients using single
nucleotide polymorphisms for candidate regions.

- Determine, using molecular methods, whether viral agents, such as human papilloma
virus, are in the causal pathway of IBMFS-associated cancers.

OUTLINE: Patients and family members complete questionnaires and undergo clinical
examinations and laboratory tests, which may include blood, bone marrow, urine, stool,
buccal scraping, oral cavity brushing, oropharynx brushing, skin biopsy, hair, deciduous
teeth, or tissue biopsies or pathology samples from tumors. Information is gathered
retrospectively through questionnaires, review of medical records, and examination of
archived materials and prospectively through additional questionnaires, clinical
examinations, and laboratory tests.

Genetic education, counseling, and germline testing, as well as disclosure of the results,
are available to patients and family members.

A certificate of confidentiality protecting the identity of research participants in this
project has been issued by the National Cancer Institute.

PROJECTED ACCRUAL: A total of 4,000 patients and family members will be accrued for this
study.