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

Sponsor:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00056121

Purpose

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.

Condition	Intervention
Cancer	Genetic: comparative genomic hybridization Genetic: cytogenetic analysis Genetic: microarray analysis Other: biologic sample preservation procedure Other: medical chart review Other: questionnaire administration

Study Type:	Observational
Official Title:	Etiologic Investigation Of Cancer Susceptibility In Inherited Bone Marrow Failure Syndromes: A Natural History Study

Resource links provided by NLM:

Genetics Home Reference related topics: Diamond-Blackfan anemia Shwachman-Diamond syndrome thrombocytopenia-absent radius syndrome

MedlinePlus related topics: Anal Cancer Anemia Bone Marrow Diseases Cancer Leukemia, Adult Acute Leukemia, Adult Chronic Leukemia, Childhood Liver Cancer Vulvar Cancer

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

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

Secondary Outcome Measures:

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

Estimated Enrollment:	4000
Study Start Date:	November 2002

Detailed Description:

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.

Eligibility

Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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) 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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00056121

Locations

United States, California
Jonsson Comprehensive Cancer Center at UCLA	Recruiting
Los Angeles, California, United States, 90095-1781
Contact: Clinical Trials Office - Jonsson Comprehensive Cancer Center a 888-798-0719
Stanford Comprehensive Cancer Center - Palo Alto	Recruiting
Palo Alto, California, United States, 94305
Contact: Steven Artandi, MD, PhD 650-736-0975
UCSF Helen Diller Family Comprehensive Cancer Center	Recruiting
San Francisco, California, United States, 94115
Contact: Clinical Trials Office - UCSF Helen Diller Family Comprehensi 877-827-3222
United States, Maryland
Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office	Recruiting
Bethesda, Maryland, United States, 20892-1182
Contact: Clinical Trials Office - Warren Grant Magnusen Clinical Center 888-NCI-1937
United States, Washington
Fred Hutchinson Cancer Research Center	Recruiting
Seattle, Washington, United States, 98109
Contact: Akiko Shimamura, MD, PhD 206-667-1127
University of Washington School of Medicine	Recruiting
Seattle, Washington, United States, 98195
Contact: Clinical Trials Office - University of Washington School of Me 206-616-8289

Sponsors and Collaborators

National Cancer Institute (NCI)

Investigators

Study Chair:

Blanche P. Alter, MD, MPH

Clinical Genetics Branch

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Web site for additional information This link exits the ClinicalTrials.gov site

Featured trial article This link exits the ClinicalTrials.gov site

Publications:

Atkinson JC, Harvey KE, Domingo DL, Trujillo MI, Guadagnini JP, Gollins S, Giri N, Hart TC, Alter BP. Oral and dental phenotype of dyskeratosis congenita. Oral Dis. 2008 Jul;14(5):419-27.

Giri N, Batista DL, Alter BP, Stratakis CA. Endocrine Abnormalities in Patients with Fanconi Anemia. J Clin Endocrinol Metab. 2007 Apr 10; [Epub ahead of print]

Rosenberg PS, Socie G, Alter BP, Gluckman E. Risk of head and neck squamous cell cancer and death in patients with Fanconi anemia who did and did not receive transplants. Blood. 2005 Jan 1;105(1):67-73. Epub 2004 Aug 26.

Rosenberg PS, Huang Y, Alter BP. Individualized risks of first adverse events in patients with Fanconi anemia. Blood. 2004 Jul 15;104(2):350-5. Epub 2004 Apr 1.

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.

Alter BP, Baerlocher GM, Savage SA, Chanock SJ, Weksler BB, Willner JP, Peters JA, Giri N, Lansdorp PM. Very short telomere length by flow fluorescence in situ hybridization identifies patients with dyskeratosis congenita. Blood. 2007 Sep 1;110(5):1439-47. Epub 2007 Apr 27.

Alter BP, Rosenberg PS, Brody LC. Clinical and molecular features associated with biallelic mutations in FANCD1/BRCA2. J Med Genet. 2007 Jan;44(1):1-9. Epub 2006 Jul 6.

Giri N, Pitel PA, Green D, Alter BP. Splenic peliosis and rupture in patients with dyskeratosis congenita on androgens and granulocyte colony-stimulating factor. Br J Haematol. 2007 Sep;138(6):815-7. No abstract available.

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

Alter BP. The association between FANCD1/BRCA2 mutations and leukaemia. Br J Haematol. 2006 May;133(4):446-8; author reply 448. No abstract available.

Braun M, Giri N, Alter BP, Cowen EW. Thrombocytopenia, multiple mucosal squamous cell carcinomas, and dyspigmentation. J Am Acad Dermatol. 2006 Jun;54(6):1056-9. No abstract available.

Alter BP. Fanconi's anemia, transplantation, and cancer. Pediatr Transplant. 2005 Dec;9 Suppl 7:81-6.

Alter BP, Joenje H, Oostra AB, Pals G. Fanconi anemia: adult head and neck cancer and hematopoietic mosaicism. Arch Otolaryngol Head Neck Surg. 2005 Jul;131(7):635-9. No abstract available.

Rosenberg PS, Alter BP, Socie G, Gluckman E. Secular trends in outcomes for Fanconi anemia patients who receive transplants: implications for future studies. Biol Blood Marrow Transplant. 2005 Sep;11(9):672-9.

Alter BP. Growth hormone and the risk of malignancy. Pediatr Blood Cancer. 2004 Oct;43(5):534-5. No abstract available.

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, Westra WH, Alter BP, Sidransky D, Koch WM, Califano JA. 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. 2004 Apr;26(4):345-52.

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

Alter BP, Greene MH, Velazquez I, Rosenberg PS. Cancer in Fanconi anemia. Blood. 2003 Mar 1;101(5):2072. No abstract available.

Rosenberg PS, Greene MH, Alter BP. Cancer incidence in persons with Fanconi anemia. Blood. 2003 Feb 1;101(3):822-6. Epub 2002 Sep 5. Erratum in: Blood. 2003 Mar 15;101(6):2136.

Study ID Numbers:	CDR0000276572, NCI-02-C-0052
Study First Received:	March 6, 2003
Last Updated:	September 26, 2009
ClinicalTrials.gov Identifier:	NCT00056121 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

secondary acute myeloid leukemia
secondary myelodysplastic syndromes
unspecified adult solid tumor, protocol specific
unspecified childhood solid tumor, protocol specific
congenital amegakaryocytic thrombocytopenia
Diamond-Blackfan anemia
dyskeratosis congenita
Fanconi anemia
IVIC syndrome
myelocerebellar disorder
Pearson marrow-pancreas syndrome
radioulnar synostosis
Revesz syndrome
severe congenital neutropenia
Shwachman-Diamond syndrome

thrombocytopenia-absent radius syndrome
WT limb-blood syndrome
stage 0 laryngeal cancer
stage IV vulvar cancer
advanced adult primary liver cancer
localized resectable adult primary liver cancer
localized unresectable adult primary liver cancer
recurrent adult primary liver cancer
recurrent childhood liver cancer
stage I childhood liver cancer
stage II childhood liver cancer
stage III childhood liver cancer
stage IV childhood liver cancer
recurrent lymphoepithelioma of the oropharynx
recurrent squamous cell carcinoma of the oropharynx

ClinicalTrials.gov processed this record on November 09, 2009