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Phenotypic Heterogeneity in Multiple Myeloma Families

From the Creighton University School of Medicine; University of Nebraska Medical Center, Omaha, NE; Weill Medical College of Cornell University; Our Lady of Mercy Cancer Center, New York Medical College, New York, NY; University of Chicago, Chicago, IL; Institut Paoli-Calmettes, Marseille, France; and University of Toronto, Toronto, Ontario, Canada

Address reprint requests to Henry T. Lynch, MD, Department of Preventive Medicine, Creighton University School of Medicine, 2500 California Plaza, Omaha, Nebraska 68178; e-mail: htlynch{at}creighton.edu

PURPOSE: To describe a series of families with familial multiple myeloma (MM). Observations were used to generate hypotheses about the role of genetic factors, the mode of inheritance of these factors, and the association of other cancers with familial MM.

PATIENTS AND METHODS: This observational study consisted of 39 families with multiple cases of MM or related disorders from four collaborating research centers. Each center followed its usual family study method. Probands were interviewed, and, when possible, cancers were verified by medical records and pathology review. A working pedigree was compiled on each family.

RESULTS: Seventeen families had affected members in two or more generations, and eight families had two or more affected members in a single generation. Four families had two or more members with plasma cell dyscrasias, with or without a single case of MM. In the remaining 10 families, a single MM case occurred with a family history of other cancers. Other cancers observed in family members included hematologic malignancies and solid tumors. In families with MM in multiple generations, there was a decrease in the age at MM diagnosis in successive generations.

CONCLUSION: The study of familial MM may provide insights into the pathogenesis and, ultimately, the control and prevention of MM and related disorders. Population-based epidemiologic studies are crucial, but because of the rarity of familial MM, a concerted case-finding approach may also be fruitful. Therefore, we propose an international consortium to study familial MM, and we invite all interested colleagues to participate.

Supported by revenue from Nebraska cigarette taxes awarded to Creighton University and the University of Nebraska Medical Center by the Nebraska Department of Health and Human Services. Support was also provided through National Institutes of Health grant Nos. 1U01 CA86389 and CA36727.

The contents of this article are solely the responsibility of the authors and do not necessarily represent the official views of the state of Nebraska or the Nebraska Department of Health and Human Services.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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