Study of Individuals and Families at High Risk for Cancer - Full Text View

Sponsored by:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00004007

Purpose

RATIONALE: Studying individuals and families at high risk for cancer may help to identify other persons at risk and identify cancer genes.

PURPOSE: This clinical trial is studying genetic and environmental factors related to cancer risk in individuals and families at high risk for cancer.

Condition	Intervention
Bladder Cancer Brain and Central Nervous System Tumors Chordoma Lung Cancer Non-Melanomatous Skin Cancer Retinoblastoma Sarcoma	Genetic: comparative genomic hybridization Genetic: gene rearrangement analysis Genetic: genetic linkage analysis Genetic: mutation analysis Other: laboratory biomarker analysis Other: questionnaire administration

Genetics Home Reference related topics: bladder cancer retinoblastoma

MedlinePlus related topics: Bladder Cancer Cancer Lung Cancer Skin Cancer Soft Tissue Sarcoma

U.S. FDA Resources

Study Type:	Observational
Official Title:	Clinical, Laboratory and Epidemiologic Characterization of Individuals and Families at High Risk of Cancer

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

Estimated Enrollment:	7500
Study Start Date:	January 1978
Estimated Primary Completion Date:	December 2020 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

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

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.

PROJECTED ACCRUAL: 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.

Eligibility

Ages Eligible for Study:	up to 95 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

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

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)

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: NCT00004007

Locations

United States, Maryland
NCI - Division of Cancer Epidemiology and Genetics	Recruiting
Bethesda, Maryland, United States, 20892
Contact: Genetic Epidemiology Branch Referral Nurse 800-518-8474
Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office	Recruiting
Bethesda, Maryland, United States, 20892-1182
Contact: Patient Recruitment 888-NCI-1937

Sponsors and Collaborators

National Cancer Institute (NCI)

Investigators

Study Chair:

Margaret A. Tucker, MD

NCI - Genetic Epidemiology Branch

More Information

Additional Information:

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

Featured trial article This link exits the ClinicalTrials.gov site

Publications:

Ng D, Stavrou T, Liu L, Taylor MD, Gold B, Dean M, Kelley MJ, Dubovsky EC, Vezina G, Nicholson HS, Byrne J, Rutka JT, Hogg D, Reaman GH, Goldstein AM. Retrospective family study of childhood medulloblastoma. Am J Med Genet A. 2005 May 1;134(4):399-403. Erratum in: Am J Med Genet A. 2005 Jul 15;136(2):226.

Yang XR, Beerman M, Bergen AW, Parry DM, Sheridan E, Liebsch NJ, Kelley MJ, Chanock S, Goldstein AM. Corroboration of a familial chordoma locus on chromosome 7q and evidence of genetic heterogeneity using single nucleotide polymorphisms (SNPs). Int J Cancer. 2005 Sep 1;116(3):487-91.

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

Chan CC, Koch CA, Kaiser-Kupfer MI, Parry DM, Gutmann DH, Zhuang Z, Vortmeyer AO. Loss of heterozygosity for the NF2 gene in retinal and optic nerve lesions of patients with neurofibromatosis 2. J Pathol. 2002 Sep;198(1):14-20.

Patronas NJ, Courcoutsakis N, Bromley CM, Katzman GL, MacCollin M, Parry DM. Intramedullary and spinal canal tumors in patients with neurofibromatosis 2: MR imaging findings and correlation with genotype. Radiology. 2001 Feb;218(2):434-42.

Parry DM, MacCollin MM, Kaiser-Kupfer MI, Pulaski K, Nicholson HS, Bolesta M, Eldridge R, Gusella JF. Germ-line mutations in the neurofibromatosis 2 gene: correlations with disease severity and retinal abnormalities. Am J Hum Genet. 1996 Sep;59(3):529-39.

Ruttledge MH, Andermann AA, Phelan CM, Claudio JO, Han FY, Chretien N, Rangaratnam S, MacCollin M, Short P, Parry D, Michels V, Riccardi VM, Weksberg R, Kitamura K, Bradburn JM, Hall BD, Propping P, Rouleau GA. Type of mutation in the neurofibromatosis type 2 gene (NF2) frequently determines severity of disease. Am J Hum Genet. 1996 Aug;59(2):331-42.

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. 2006 Apr;43(4):e16.

Baser ME, Kuramoto L, Woods R, Joe H, Friedman JM, Wallace AJ, Ramsden RT, Olschwang S, Bijlsma E, Kalamarides M, Papi L, Kato R, Carroll J, Lazaro C, Joncourt F, Parry DM, Rouleau GA, Evans DG. The location of constitutional neurofibromatosis 2 (NF2) splice site mutations is associated with the severity of NF2. J Med Genet. 2005 Jul;42(7):540-6. Review.

Baser ME, Mautner VF, Parry DM, Evans DG. Methodological issues in longitudinal studies: vestibular schwannoma growth rates in neurofibromatosis 2. J Med Genet. 2005 Dec;42(12):903-6. Epub 2005 Apr 14. Review.

Taylor MD, Liu L, Raffel C, Hui CC, Mainprize TG, Zhang X, Agatep R, Chiappa S, Gao L, Lowrance A, Hao A, Goldstein AM, Stavrou T, Scherer SW, Dura WT, Wainwright B, Squire JA, Rutka JT, Hogg D. Mutations in SUFU predispose to medulloblastoma. Nat Genet. 2002 Jul;31(3):306-10. Epub 2002 Jun 17.

Zhao Y, Kumar RA, Baser ME, Evans DG, Wallace A, Kluwe L, Mautner VF, Parry DM, Rouleau GA, Joe H, Friedman JM. Intrafamilial correlation of clinical manifestations in neurofibromatosis 2 (NF2). Genet Epidemiol. 2002 Oct;23(3):245-59.

Kelley MJ, Korczak JF, Sheridan E, Yang X, Goldstein AM, Parry DM. Familial chordoma, a tumor of notochordal remnants, is linked to chromosome 7q33. Am J Hum Genet. 2001 Aug;69(2):454-60. Epub 2001 Jul 10.

Study ID Numbers:	CDR0000067218, NCI-78-C-0039
Study First Received:	November 1, 1999
Last Updated:	February 6, 2009
ClinicalTrials.gov Identifier:	NCT00004007 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

Ewing sarcoma/peripheral primitive neuroectodermal tumor (PNET)
small cell lung cancer
non-small cell lung cancer
childhood brain tumor
osteosarcoma

basal cell carcinoma of the skin
retinoblastoma
adult brain tumor
bladder cancer
chordoma

Study placed in the following topic categories:

Retinal Neoplasms
Thoracic Neoplasms
Urinary Tract Neoplasm
Neuroectodermal Tumors, Primitive
Urogenital Neoplasms
Central Nervous System Neoplasms
Retinoblastoma
Urologic Neoplasms
Chordoma
Neoplasms, Connective and Soft Tissue
Soft Tissue Sarcomas
Sarcoma, Ewing's
Respiratory Tract Diseases
Urologic Diseases
Lung Neoplasms

Neoplasms, Germ Cell and Embryonal
Osteogenic Sarcoma
Neuroepithelioma
Bladder Neoplasm
Ewing's Family of Tumors
Retinal Diseases
Nervous System Neoplasms
Cystocele
Eye Neoplasms
Skin Diseases
Eye Diseases
Urinary Bladder Diseases
Urinary Bladder Neoplasms
Brain Tumor, Childhood
Osteosarcoma

Additional relevant MeSH terms:

Retinal Neoplasms
Thoracic Neoplasms
Neoplasms, Nerve Tissue
Urogenital Neoplasms
Central Nervous System Neoplasms
Urologic Neoplasms
Retinoblastoma
Chordoma
Neoplasms, Connective and Soft Tissue
Neoplasms by Site
Urologic Diseases
Respiratory Tract Diseases
Lung Neoplasms
Neoplasms, Germ Cell and Embryonal
Retinal Diseases

Nervous System Neoplasms
Respiratory Tract Neoplasms
Neoplasms by Histologic Type
Eye Neoplasms
Skin Diseases
Eye Diseases
Urinary Bladder Diseases
Nervous System Diseases
Urinary Bladder Neoplasms
Skin Neoplasms
Neuroectodermal Tumors
Neoplasms
Lung Diseases
Sarcoma
Neoplasms, Neuroepithelial

ClinicalTrials.gov processed this record on May 07, 2009