title: Phenotypic heterogeneity in multiple myeloma families.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Creighton University School of Medicine, 2500 California Plaza, Omaha, Nebraska 68178, USA. htlynch@creighton.edu
authors.forename: Henry T
authors.initials: HT
authors.lastname: Lynch
authors.forename: Patrice
authors.initials: P
authors.lastname: Watson
authors.forename: Stefano
authors.initials: S
authors.lastname: Tarantolo
authors.forename: Peter H
authors.initials: PH
authors.lastname: Wiernik
authors.forename: Brigid
authors.initials: B
authors.lastname: Quinn-Laquer
authors.forename: Karin
authors.initials: K
authors.lastname: Isgur Bergsagel
authors.forename: Laetitia
authors.initials: L
authors.lastname: Huiart
authors.forename: O I
authors.initials: OI
authors.lastname: Olopade
authors.forename: Hagay
authors.initials: H
authors.lastname: Sobol
authors.forename: Warren
authors.initials: W
authors.lastname: Sanger
authors.forename: David
authors.initials: D
authors.lastname: Hogg
authors.forename: Dennis
authors.initials: D
authors.lastname: Weisenburger
mesh_terms: D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype