Etiological Investigation of Cancer Susceptibility in Inherited Bone Marrow Failure Syndromes: A Natural History Study

Background:

A prospective cohort of Inherited Bone Marrow Failure Syndrome (IBMFS) will provide new information regarding cancer rates and types in these disorders.
Mutations in IBMFS genes are relevant to carcinogenesis in sporadic cancers.
Patients with IBMFS who develop cancer differ in their genetic and/or environmental features from patients with IBMFS who do not develop cancer.
These cancer-prone families are well suited for cancer screening and prevention trials targeting those at increased genetic risk of cancer.
Carriers of IBMFS gene mutations are at increased risk of cancer.
The prototype disorder is Fanconi Anemia (FA); other IBMFS will also be studied.

Objectives:

To determine the types and incidence of specific cancers in patients with an IBMFS.
To investigate the relevance of IBMFS gene mutations in the carcinogenesis pathway of the sporadic counterparts of IBMFS-associated cancers.
To identify risk factors for IBMFS-related cancers in addition to the primary germline mutations.
To determine the risk of cancer in IBMFS carriers.

Design:

Natural history study, with questionnaires, clinical evaluations, clinical and research laboratory tests, review of medical records, cancer surveillance.
Primary endpoints are all cancers, solid tumors, and cancers specific to each type of IBMFS.
Secondary endpoints are markers of pre-malignant conditions, such as leukoplakia, serum or tissue evidence of carcinogenic viruses, and bone marrow morphologic myelodyplastic syndrome or cytogenetic clones.