Familiality of benign and malignant paraproteinemias. A population-based cancer-registry study of multiple myeloma families.

BACKGROUND AND OBJECTIVES: The occurrence of two or more cases of multiple myeloma (MM) in the same family has been reported from time to time. The current study is the first population- and cancer-registry-based survey to investigate familiality of premalignant or malignant B-cell proliferation. DESIGN AND METHODS: A family registry of 218 multiple myeloma cases was compared with the records of the Icelandic Cancer Registry in order to analyze the pedigrees for the occurrence of families with multiple cases of paraproteinemia and hematologic malignancies. RESULTS: The relative risk of developing monoclonal gammopathies of unknown significance (MGUS) was not increased among first-degree relatives of MM patients, but there was a significantly increased risk of developing MM for females separately (RR = 3.23, CI 1.17-7.01) and for males and females combined (RR = 2.33, CI 1.12-4.26). Analysis for all hematologic malignancies showed an increased risk for female relatives of MM patients (RR = 1.95, CI 1.10-3.20). Eight families were identified in which the propositus with MM had > 1 relatives with MGUS and > 1 with another hematologic malignancy, including 4 families with another relative with MM. In three families both myeloid and lymphoid malignancies occurred. INTERPRETATION AND CONCLUSIONS: Although inheritance does not appear to be a major risk factor for the development of paraproteinemias a significant risk of developing MM was found for female relatives. The occurrence of multiple cases of benign and malignant paraproteinemias in a few families does suggest a hereditary contribution. Further studies of such families might reveal clues on pathogenesis.

Monoclonal gammopathy in Iceland: a population-based registry and follow-up.

The term monoclonal gammopathy (MG) signifies the benign or malignant clonal growth of B lymphocytes. In the present study, monoclonal gammopathy of unknown significance (MGUS) was defined as those patients with no identified haematological malignancy. A database was constructed of all 713 MG patients in Iceland between 1976 and 1997 and compared with the Icelandic Cancer Registry. The age-standardized incidence per 100 000 of MG was 10.3 for males and 8.6 for females, calculated for the whole period, rising steadily from 5.8 (men) and 4.9 (women) during the 5-year period 1976-80 to 14.7 (men) and 12.5 (women) during the last 5 year period. Age-standardized incidence rates were very low for subjects under 50 years of age, then increased with age from 11 and 17 per 100 000 at 50-54, to 169 and 119 per 100 000 at age 80-84, for men and women respectively. No association was detected between MG and non-haematological malignancies, neither retrospectively nor prospectively. Haematological malignancy was diagnosed in 209 (29.3%) cases before the recorded finding of MG or within the same calendar year, leaving 504 (70.7%) patients diagnosed with MGUS. Of these, 51 (10%) progressed to multiple myeloma or Waldenström's macroglobulinaemia after a mean interval of 3.8 years; mean follow-up was 7.4 years, median 6 years. The most common immunoglobulin (Ig) class was IgG (55%), followed by IgM (32%) and IgA (13%). MGUS was a highly significant risk factor for developing haematological malignancies and the risk was significantly greater for MG of the IgA class compared with either IgG or IgM.