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

Alternate Title

Study of Individuals and Families at High Risk for Cancer

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
No phase specified	Biomarker/Laboratory analysis, Genetics, Natural history/Epidemiology	Active	1 month to 95 years	NCI	NCI-78-C-0039 NCT00004007

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

Objectives

1. Identify individuals at high risk of cancer, especially due to personal or family medical history.
2. Evaluate and define clinical spectrum of disease in syndromes predisposing to cancer.
3. Quantify risks of tumors in family members.
4. Map, clone, and determine function of tumor susceptibility genes.
5. Identify genetic determinants and gene-environmental interactions conferring cancer risk in individuals and families.
6. Evaluate gene-gene and gene-environmental interactions in tumor formation.
7. Evaluate potential precursor states of disease in families at risk of cancer.

Entry Criteria

Disease Characteristics:

• Family or personal medical history of neoplasia of unusual type, pattern, or number
  • Two or more living affected cases among family members are required
  • The following types of familial cancers are eligible:
    • Bone (non-neuroaxis, such as osteosarcoma)
    • Bladder
    • Brain
    • Chordoma
    • Lung
    • Nevoid basal cell carcinoma syndrome (NBCC)
  • The following type of familial benign neoplasm is eligible:
    • Neurofibromatosis type 2 (bilateral acoustic neurofibromatosis)

  OR




• Known or suspected factor(s) predisposing to neoplasia, meeting 1 of the following criteria:
  • Environmental exposure, including:
    • Medications
    • Occupation
    • Radiation
    • Diet
    • Infectious agents
  • Genetic and/or congenital factors, including:
    • Birth defects
    • Metabolic phenotype
    • Chromosomal anomalies
    • Mendelian traits associated with tumors
  • Unusual demographic features, including:
    • Very young age of onset
    • Multiple tumors



• Personal and family medical history must be verified through questionnaires, interviews, and review of pathology slides and medical records



• Ineligible for familial melanoma, lymphoproliferative, breast-ovarian cancer, or testicular cancer protocols

Prior/Concurrent Therapy:

Biologic therapy

• Not specified

Chemotherapy

• Not specified

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified

Patient Characteristics:

Age:

• 1 month to 95 years

Performance status:

• Not specified

Life expectancy:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• Not specified

Renal:

• Not specified

Other:

• Not pregnant (for parts of protocol involving ionizing radiation or magnetic fields)

Expected Enrollment

A total of 7,500 individuals will be accrued for this study. Substudies, involving subsets of the 7,500 individuals, are part of the overall study design.

Outline

One family member completes a family history questionnaire for verification of diagnosis and construction of a family pedigree. Individuals and families undergo clinical evaluation comprising at least a medical history, physical examination, and testing of blood specimens. Other biologic specimens may also be obtained from some individuals, and some individuals may undergo other diagnostic studies and examinations, depending on the type of familial neoplasm being studied.

If a family is already participating in the study and a specific mutation in a tumor predisposing gene predictive of disease has already been identified in the family, individuals may be eligible for genetic testing. Genes tested include RB1, APC, BRCA1/2, NF2, and VHL. Individuals under age 18 are only eligible to be tested for APC (familial adenomatous polyposis), NF2 (neurofibromatosis type 2), PTCH (nevoid basal cell carcinoma syndrome), RB1 (retinoblastoma), and VHL (von Hippel-Lindau disease).

Individuals may receive results of the genetic testing and genetic counseling is offered to all individuals who are tested.

A certificate of confidentiality protecting the identity of research participants in this project has been issued by the National Cancer Institute.

Families are followed every 1-2 years. In selected instances, individuals and families may return to the Clinical Center periodically for study-specific follow-up evaluations.

Ng D, Stavrou T, Liu L, et al.: Retrospective family study of childhood medulloblastoma. Am J Med Genet A 134 (4): 399-403, 2005.[PUBMED Abstract]

Yang XR, Beerman M, Bergen AW, et al.: Corroboration of a familial chordoma locus on chromosome 7q and evidence of genetic heterogeneity using single nucleotide polymorphisms (SNPs). Int J Cancer 116 (3): 487-91, 2005.[PUBMED Abstract]

Baser ME, Makariou EV, Parry DM: Predictors of vestibular schwannoma growth in patients with neurofibromatosis Type 2. J Neurosurg 96 (2): 217-22, 2002.[PUBMED Abstract]

Chan CC, Koch CA, Kaiser-Kupfer MI, et al.: Loss of heterozygosity for the NF2 gene in retinal and optic nerve lesions of patients with neurofibromatosis 2. J Pathol 198 (1): 14-20, 2002.[PUBMED Abstract]

Patronas NJ, Courcoutsakis N, Bromley CM, et al.: Intramedullary and spinal canal tumors in patients with neurofibromatosis 2: MR imaging findings and correlation with genotype. Radiology 218 (2): 434-42, 2001.[PUBMED Abstract]

Parry DM, MacCollin MM, Kaiser-Kupfer MI, et al.: Germ-line mutations in the neurofibromatosis 2 gene: correlations with disease severity and retinal abnormalities. Am J Hum Genet 59 (3): 529-39, 1996.[PUBMED Abstract]

Ruttledge MH, Andermann AA, Phelan CM, et al.: Type of mutation in the neurofibromatosis type 2 gene (NF2) frequently determines severity of disease. Am J Hum Genet 59 (2): 331-42, 1996.[PUBMED Abstract]

R Yang X, Pfeiffer RM, Goldstein AM: Influence of glutathione-S-transferase (GSTM1, GSTP1, GSTT1) and cytochrome p450 (CYP1A1, CYP2D6) polymorphisms on numbers of basal cell carcinomas (BCCs) in families with the naevoid basal cell carcinoma syndrome. J Med Genet 43 (4): e16, 2006.[PUBMED Abstract]

Baser ME, Kuramoto L, Woods R, et al.: The location of constitutional neurofibromatosis 2 (NF2) splice site mutations is associated with the severity of NF2. J Med Genet 42 (7): 540-6, 2005.[PUBMED Abstract]

Baser ME, Mautner VF, Parry DM, et al.: Methodological issues in longitudinal studies: vestibular schwannoma growth rates in neurofibromatosis 2. J Med Genet 42 (12): 903-6, 2005.[PUBMED Abstract]

Taylor MD, Liu L, Raffel C, et al.: Mutations in SUFU predispose to medulloblastoma. Nat Genet 31 (3): 306-10, 2002.[PUBMED Abstract]

Zhao Y, Kumar RA, Baser ME, et al.: Intrafamilial correlation of clinical manifestations in neurofibromatosis 2 (NF2). Genet Epidemiol 23 (3): 245-59, 2002.[PUBMED Abstract]

Kelley MJ, Korczak JF, Sheridan E, et al.: Familial chordoma, a tumor of notochordal remnants, is linked to chromosome 7q33. Am J Hum Genet 69 (2): 454-60, 2001.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

NCI - Center for Cancer Research

Margaret Tucker, MD, Protocol chair		Ph: 301-496-4375

U.S.A.
Maryland
	Bethesda
	NCI - Division of Cancer Epidemiology and Genetics
		Genetic Epidemiology Branch Referral Nurse	Ph:  800-518-8474
	Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
		Patient Recruitment	Ph:  888-NCI-1937

Related Information

Featured trial article

Registry Information
Official Title		Clinical, Laboratory and Epidemiologic Characterization of Individuals and Families at High Risk of Cancer
Trial Start Date		1978-01-01
Trial Completion Date		2020-12-31 (estimated)
Registered in ClinicalTrials.gov		NCT00004007
Date Submitted to PDQ		1999-07-08
Information Last Verified		2009-06-07

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