RATIONALE: Evaluating genetic and environmental factors in individuals and families at high risk of developing hematologic cancer may help doctors plan more effective treatments.

PURPOSE: Screening trial to determine if genetic and environmental factors contribute to the development of hematologic cancer in individuals and families at high risk for cancer.

OBJECTIVES:

• Ascertain individuals at high risk for hematologic malignancy because of personal or family medical history.
• Evaluate and define the clinical spectrum and natural history of disease in syndromes predisposing these individuals and families to hematologic cancer.
• Evaluate the potential precursor states of malignancy in families at risk.
• Quantify the risks of specific tumors in family members of this high-risk population and define syndromic constellations.
• Identify, map, characterize, clone, and determine function of tumor susceptibility genes in this high-risk population.
• Validate and test associations of biomarkers with risk in these individuals.
• Identify genetic determinants, environmental factors, and gene-environmental interactions conferring cancer risk in individuals and families.
• Identify differences and similarities between the familial and sporadic condition in this high-risk population.
• Educate and counsel study participants about their risk of hematologic malignancy including prevention recommendations and early detection activities when known.

OUTLINE: One family member completes a family history questionnaire. Participants may undergo limited physical exams, imaging studies, and skin or bone marrow biopsy.

Blood is collected for localizing genetic loci, identifying genes, and evaluating genotype/phenotype correlations. Buccal cells are obtained for germline DNA extraction.

Participants receive counseling and education for cancer prevention, risk reduction, and early detection.

Participants are followed approximately annually for as long as possible.

PROJECTED ACCRUAL: A total of 3,000 patients will be accrued for this study.

• Leukemia
• Lymphoma
• Lymphoproliferative Disorder
• Multiple Myeloma and Plasma Cell Neoplasm
• Myelodysplastic Syndromes
• Myelodysplastic/Myeloproliferative Diseases

• Genetic: genetic linkage analysis
• Genetic: microarray analysis
• Other: counseling intervention
• Other: laboratory biomarker analysis
• Other: questionnaire administration
• Procedure: evaluation of cancer risk factors

• McMaster ML, Giambarresi T, Vasquez L, Goldstein AM, Tucker MA. Cytogenetics of familial Waldenstrom's macroglobulinemia: in pursuit of an understanding of genetic predisposition. Clin Lymphoma. 2005 Mar;5(4):230-4.
• Marti GE, Carter P, Abbasi F, Washington GC, Jain N, Zenger VE, Ishibe N, Goldin L, Fontaine L, Weissman N, Sgambati M, Fauget G, Bertin P, Vogt RF Jr, Slade B, Noguchi PD, Stetler-Stevenson MA, Caporaso N. B-cell monoclonal lymphocytosis and B-cell abnormalities in the setting of familial B-cell chronic lymphocytic leukemia. Cytometry. 2003 Mar;52B(1):1-12.
• Caporaso N, Marti GE, Goldin L. Perspectives on familial chronic lymphocytic leukemia: genes and the environment. Semin Hematol. 2004 Jul;41(3):201-6. Review.
• Chatterjee N, Hartge P, Cerhan JR, Cozen W, Davis S, Ishibe N, Colt J, Goldin L, Severson RK. Risk of non-Hodgkin's lymphoma and family history of lymphatic, hematologic, and other cancers. Cancer Epidemiol Biomarkers Prev. 2004 Sep;13(9):1415-21.
• Goldin LR, Pfeiffer RM, Gridley G, Gail MH, Li X, Mellemkjaer L, Olsen JH, Hemminki K, Linet MS. Familial aggregation of Hodgkin lymphoma and related tumors. Cancer. 2004 May 1;100(9):1902-8.
• Goldin LR, Pfeiffer RM, Li X, Hemminki K. Familial risk of lymphoproliferative tumors in families of patients with chronic lymphocytic leukemia: results from the Swedish Family-Cancer Database. Blood. 2004 Sep 15;104(6):1850-4. Epub 2004 May 25.
• Pfeiffer RM, Goldin LR, Chatterjee N, Daugherty S, Hemminki K, Pee D, X LI, Gail MH. Methods for testing familial aggregation of diseases in population-based samples: application to Hodgkin lymphoma in Swedish registry data. Ann Hum Genet. 2004 Sep;68(Pt 5):498-508.
• Goldin LR, Ishibe N, Sgambati M, Marti GE, Fontaine L, Lee MP, Kelley JM, Scherpbier T, Buetow KH, Caporaso NE. A genome scan of 18 families with chronic lymphocytic leukaemia. Br J Haematol. 2003 Jun;121(6):866-873.
• Ishibe N, Prieto D, Hosack DA, Lempicki RA, Goldin LR, Raffeld M, Marti GE, Caporaso NE. Telomere length and heavy-chain mutation status in familial chronic lymphocytic leukemia. Leuk Res. 2002 Sep;26(9):791-4.

DISEASE CHARACTERISTICS:

• Meets one of the following criteria:

  • Family or personal medical history of hematologic/lymphoproliferative malignancy of an unusual type, pattern, or number
  • Known or suspected factor(s) predisposing to hematologic malignancy
  • Genetic and/or congenital (e.g., birth defects, metabolic phenotype, chromosomal anomalies, or Mendelian traits associated with tumors)
  • Environmental exposure (e.g., medications, occupation, radiation, diet, or infectious agents)
  • Unusual demographic features (e.g., very young age at onset or multiple tumors)

• Familial aggregation of any of the following:

  • Chronic lymphocytic leukemia
  • Waldenstrom's macroglobulinemia (WM)
  • Non-Hodgkin's lymphoma
  • Hodgkin's lymphoma
  • Mixed hematologic and lymphoproliferative diseases
  • Any other hematologic cancer

• At least 2 living affected family members required for familial neoplasms

  • For WM, one case plus a living first-degree relative with an autoimmune condition is required

PATIENT CHARACTERISTICS:

Age

• Any age

Performance status

• Not specified

Life expectancy

• Not specified

Hematopoietic

• Not specified

Hepatic

• Not specified

Renal

• Not specified

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• Not specified

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified