| Conditions: |
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Cancer |
| Purpose: |
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RATIONALE: Genetic studies may help in understanding the genetic processes involved in the
development of some types of cancer and may help doctors identify patients who are at risk
for cancer.
PURPOSE: Genetic study of cancer risk and gene identification in patients and families who
have Fanconi's anemia or other inherited bone marrow disorders.
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| Study Summary: |
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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.
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| Criteria: |
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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
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| NCT ID: |
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NCT00056121 |
| Primary Contact: |
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Study Chair
Blanche P. Alter, MD, MPH
Clinical Genetics Branch
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| Backup Contact: |
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N/A |
| Location Contact: |
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San Francisco, California 94115
United States
Clinical Trials Office - UCSF Helen Diller Family Comprehensi
Phone: 877-827-3222
Site Status: Recruiting |