• Cancer, leukemia, or aplastic anemia as measured by blood counts, bone marrow, and other exams annually
  

• Evolution from current status as determined by blood counts, bone marrow, and other exams annually
  

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.

DISEASE CHARACTERISTICS:

• Suspected (at the investigator's discretion) or proven diagnosis of 1 of the following inherited bone marrow failure syndromes (IBMFS):

  • Fanconi's anemia
  • Diamond-Blackfan anemia
  • Dyskeratosis congenita
  • Shwachman-Diamond syndrome
  • Amegakaryocytic thrombocytopenia
  • Thrombocytopenia absent radii
  • Severe congenital neutropenia
  • Pearson's syndrome
  • Other IBMFS (including Revesz, WT limb-blood syndrome, IVIC syndrome, radio-ulnar synostosis, and ataxia-pancytopenia) OR
• First-degree relatives (i.e., full or half siblings, biologic parents, and children) and grandparents of IBMFS patients OR
• Patients in the general population diagnosed with a sporadic tumor of the type seen in IBMFS (head and neck, gastrointestinal, or anogenital cancer) with none of the usual risk factors for that tumor (e.g., smoking, drinking, or human papilloma viral infection)
• No evidence that the hematologic disorder is acquired (e.g., temporal relation of aplastic anemia to known marrow suppressant drugs, chemicals, toxins, or viruses) in the absence of evidence indicative of an inherited marrow failure disorder

• No known causes of cytopenias, including any of the following:

  • Autoantibodies to red blood cells, platelets, or neutrophils
  • Viruses (especially hepatitis)
  • Micronutrient deficiencies
  • Transient erythroblastopenia of childhood
  • Cyclic neutropenia
• No physical findings indicative of other syndromes or causes that are not part of the IBMFS disease spectrum

PATIENT CHARACTERISTICS:

Age

• Any age

Performance status

• Not specified

Life expectancy

• Not specified

Hematopoietic

• See Disease Characteristics

Hepatic

• See Disease Characteristics

Renal

• Not specified

Other

• Able and willing to complete questionnaires and permit access to medical records and pathology specimens

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• Not specified

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified