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Clinical Trials (PDQ®)

Genetic and Etiology Study of Cancer Susceptibility in Patients With Inherited Disorders of the Bone Marrow and Their Families

Alternate Title
Basic Trial Information
Entry Criteria
Expected Enrollment
Published Results
Related Publications
Trial Contact Information
Related Information
Registry Information

Alternate Title

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

Basic Trial Information

PhaseTypeStatusAgeSponsorProtocol IDs
No phase specifiedGenetics, Natural history/EpidemiologyActiveAny ageNCINCI-02-C-0052

Special Category: NCI Web site featured trial, NIH Clinical Center trial, NCI Web site featured trial


  1. 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.
  2. Determine the specific types of cancer associated with each type of IBMFS.
  3. Compare the biology of incident and prevalent tumors in IBMFS patients vs their sporadic counterparts in the general population.
  4. 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.
  5. 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.
  6. Determine the risk of cancer in individuals who are carriers of FA or other IBMFS gene mutations.
  7. Compare cellular and molecular characteristics of tumor biopsies and specimens from IBMFS patients vs cancers in the same tissues from the general population.
  8. Compare myelodysplastic syndromes (MDS) in these patients vs primary and secondary MDS in the general adult and pediatric population.
  9. 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.
  10. Search for genes that might modify cancer susceptibility in these patients using single nucleotide polymorphisms for candidate regions.
  11. Determine, using molecular methods, whether viral agents, such as human papilloma virus, are in the causal pathway of IBMFS-associated cancers.

Entry Criteria

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)


  • First-degree relatives (i.e., full or half siblings, biologic parents, and children) and grandparents of IBMFS patients


  • 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

Prior/Concurrent Therapy:

Biologic therapy

  • Not specified


  • Not specified

Endocrine therapy

  • Not specified


  • Not specified


  • Not specified

Patient Characteristics:


  • Any age

Performance status

  • Not specified

Life expectancy

  • Not specified


  • See Disease Characteristics


  • See Disease Characteristics


  • Not specified


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

Expected Enrollment


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


Primary Outcome(s)

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

Secondary Outcome(s)

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


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.

Published Results

Atkinson JC, Harvey KE, Domingo DL, et al.: Oral and dental phenotype of dyskeratosis congenita. Oral Dis 14 (5): 419-27, 2008.[PUBMED Abstract]

Giri N, Batista DL, Alter BP, et al.: Endocrine abnormalities in patients with Fanconi anemia. J Clin Endocrinol Metab 92 (7): 2624-31, 2007.[PUBMED Abstract]

Rosenberg PS, Socié G, Alter BP, et al.: Risk of head and neck squamous cell cancer and death in patients with Fanconi anemia who did and did not receive transplants. Blood 105 (1): 67-73, 2005.[PUBMED Abstract]

Rosenberg PS, Huang Y, Alter BP: Individualized risks of first adverse events in patients with Fanconi anemia. Blood 104 (2): 350-5, 2004.[PUBMED Abstract]

Socie G, Rosenberg P, Gluckman B, et al.: How can we quantify the risk of squamous cell cancer (SCC) and death in transplanted versus non-transplanted patients with Fanconi's anaemia. [Abstract] Bone Marrow Transplant 33 (Suppl 1): S27, 2004.

Related Publications

Alter BP, Baerlocher GM, Savage SA, et al.: Very short telomere length by flow fluorescence in situ hybridization identifies patients with dyskeratosis congenita. Blood 110 (5): 1439-47, 2007.[PUBMED Abstract]

Alter BP, Rosenberg PS, Brody LC: Clinical and molecular features associated with biallelic mutations in FANCD1/BRCA2. J Med Genet 44 (1): 1-9, 2007.[PUBMED Abstract]

Giri N, Pitel PA, Green D, et al.: Splenic peliosis and rupture in patients with dyskeratosis congenita on androgens and granulocyte colony-stimulating factor. Br J Haematol 138 (6): 815-7, 2007.[PUBMED Abstract]

Hutson SP, Alter BP: Experiences of siblings of patients with Fanconi anemia. Pediatr Blood Cancer 48 (1): 72-9, 2007.[PUBMED Abstract]

Alter BP: The association between FANCD1/BRCA2 mutations and leukaemia. Br J Haematol 133 (4): 446-8; author reply 448, 2006.[PUBMED Abstract]

Braun M, Giri N, Alter BP, et al.: Thrombocytopenia, multiple mucosal squamous cell carcinomas, and dyspigmentation. J Am Acad Dermatol 54 (6): 1056-9, 2006.[PUBMED Abstract]

Alter BP: Fanconi's anemia, transplantation, and cancer. Pediatr Transplant 9 (Suppl 7): 81-6, 2005.[PUBMED Abstract]

Alter BP, Joenje H, Oostra AB, et al.: Fanconi anemia: adult head and neck cancer and hematopoietic mosaicism. Arch Otolaryngol Head Neck Surg 131 (7): 635-9, 2005.[PUBMED Abstract]

Rosenberg PS, Alter BP, Socié G, et al.: Secular trends in outcomes for Fanconi anemia patients who receive transplants: implications for future studies. Biol Blood Marrow Transplant 11 (9): 672-9, 2005.[PUBMED Abstract]

Alter BP: Growth hormone and the risk of malignancy. Pediatr Blood Cancer 43 (5): 534-5, 2004.[PUBMED Abstract]

Alter BP, Joenje H, Oostra AB, et al.: Fanconi's anemia (FA): first diagnosis in an adult with head and neck cancer and hematopoietic somatic mosaicism. [Abstract] 2004 Pediatric Academic Societies' Annual Meeting, May 1-4, San Francisco, California. A-1649, 2004. Available Online. Last accessed July 15, 2005.

Tong BC, Dhir K, Ha PK, et al.: Use of single nucleotide polymorphism arrays to identify a novel region of loss on chromosome 6q in squamous cell carcinomas of the oral cavity. Head Neck 26 (4): 345-52, 2004.[PUBMED Abstract]

Velazquez I, Alter BP: Androgens and liver tumors: Fanconi's anemia and non-Fanconi's conditions. Am J Hematol 77 (3): 257-67, 2004.[PUBMED Abstract]

Alter BP, Greene MH, Velazquez I, et al.: Cancer in Fanconi anemia. Blood 101 (5): 2072, 2003.[PUBMED Abstract]

Rosenberg PS, Greene MH, Alter BP: Cancer incidence in persons with Fanconi anemia. Blood 101 (3): 822-6, 2003.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

NCI - Center for Cancer Research

Blanche Alter, MD, MPH, Protocol chair
Ph: 301-594-7642

Trial Sites

  Los Angeles
 Jonsson Comprehensive Cancer Center at UCLA
 Clinical Trials Office - Jonsson Comprehensive Cancer Center at UCLA
Ph: 888-798-0719
  Palo Alto
 Stanford Comprehensive Cancer Center - Palo Alto
 Steven Artandi, MD, PhD
Ph: 650-736-0975
  San Francisco
 UCSF Helen Diller Family Comprehensive Cancer Center
 Clinical Trials Office - UCSF Helen Diller Family Comprehensive Cancer Center
Ph: 877-827-3222
 Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
 Clinical Trials Office - Warren Grant Magnusen Clinical Center - NCI Clinical Trials Referral Office
Ph: 888-NCI-1937
 Fred Hutchinson Cancer Research Center
 Akiko Shimamura, MD, PhD
Ph: 206-667-1127
 University of Washington School of Medicine
 Clinical Trials Office - University of Washington School of Medicine
Ph: 206-616-8289
United Kingdom
 King's College School of Medicine and Dentistry
 Swee Thein, MD
Ph: 44-171-274-6222

Related Information

Web site for additional information
Featured trial article

Registry Information
Official Title Etiologic Investigation Of Cancer Susceptibility In Inherited Bone Marrow Failure Syndromes: A Natural History Study
Trial Start Date 2002-11-01
Registered in NCT00056121
Date Submitted to PDQ 2001-06-12
Information Last Verified 2009-06-14

Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol.

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