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.

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.

Accepts Healthy Volunteers

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