OBJECTIVES:

• Identify key late-occurring complications, specifically, cardiac dysfunction, myocardial infarction (closed to accrual as of 6/5/06), ischemic stroke, avascular necrosis, and subsequent malignant neoplasm, in childhood cancer survivors.
• Correlate key late-occurring complications with pathology and staging of the primary malignancy and therapeutic treatment protocol details in these patients.
• Identify treatment-related and demographic risk factors by comparing patients who develop late-occurring complications (case group) vs those with the same primary malignancy who do not develop late-occurring complications (control group).
• Compare the frequency of mutations or polymorphisms in specific candidate genes in both the case and control groups using constitutional DNA and RNA from both groups.
• Explore the role and nature of gene-environment interaction in the development of late-occurring complications in these patients.

OUTLINE: This is a multicenter study.

DNA from peripheral blood or buccal sample of patients is analyzed for the presence of polymorphisms in candidate genes associated with an increased risk of late-occurring complications, such as cardiac dysfunction, myocardial infarction (closed to accrual as of 6/5/06), ischemic stroke, avascular necrosis, and subsequent malignant neoplasms.

Patients also complete a questionnaire detailing family history and health history.

PROJECTED ACCRUAL: A total of 6,900 patients (1,725 with late-occurring complications [case group] and 5,175 without late-occurring complications [control group] [myocardial infarction patients closed to accrual as of 6/5/06]) will be accrued for this study.

DISEASE CHARACTERISTICS:

• Diagnosis of primary cancer at age 21 or younger

• In active follow-up by a Children's Oncology Group (COG) institution

  • Date of last visit or contact by a COG institution within the past 24 months

• Case group

  • Development of one of the following key adverse events after initiation of prior cancer therapy:

    • Cardiac dysfunction, meeting 1 of the following criteria:

      • Symptomatic cardiac dysfunction, including current or previous diagnosis of congestive heart failure based on any of the following clinical criteria:

        • Pulmonary and/or peripheral edema
        • Dyspnea
        • Orthopnea
        • Fatigue
        • Hepatomegaly

      • Asymptomatic cardiac dysfunction

        • Ejection fraction < 40% on echocardiogram OR MUGA and/or fractional shortening < 28% on echocardiogram without clinical symptoms

    • Myocardial infarction, meeting 1 of the following criteria (closed to accrual as of 6/5/06):

      • Definite ECG changes
      • Typical, atypical, or inadequately described symptoms AND probable ECG, AND abnormal enzymes, including creatine kinase MB
      • Typical symptoms AND abnormal enzymes, including creatine kinase MB, AND ischemic ECG, non-codable ECG, or ECG not available

    • Ischemic stroke, meeting the following criteria:

      • Fixed neurological deficit lasting more than 24 hours
      • Confirmed by CT scan or MRI within 7 days of onset of symptoms
      • No subarachnoid or intracerebral hemorrhage, transient ischemic attacks, or amaurosis fugax

    • Avascular necrosis, meeting the following criteria:

      • Clinical symptoms of joint pain, joint stiffness, or decreased range of motion
      • Confirmed by plain radiographs, CT scan, MRI, or bone scan

    • Subsequent malignant neoplasm, meeting the following criteria:

      • Histologically distinct neoplasm developing in patients treated for a primary cancer
      • Confirmed by an institutional pathology report

• Control group

  • No clinical evidence of any of the following:

    • Cardiac dysfunction
    • Myocardial infarction (closed to accrual as of 6/5/06)
    • Ischemic stroke
    • Avascular necrosis
    • Subsequent malignant neoplasm

PATIENT CHARACTERISTICS:

Age

• 21 and under at diagnosis, any age at study entry

Performance status

• Not specified

Life expectancy

• Not specified

Hematopoietic

• Not specified

Hepatic

• Not specified

Renal

• Not specified

Cardiovascular

• See Disease Characteristics

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• Not specified

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified

Other

• No prior allogeneic (non-autologous) hematopoietic cell transplant