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.

Epidemiology of hairy cell leukemia in Iceland.

INTRODUCTION: Hairy cell leukemia (HCL) is a rare B-cell lymphoproliferative disorder. Previous epidemiological studies have mainly focused on cases derived from single institutions or from localized cancer registries. This is the first study in which all cases diagnosed nationwide over a long period of time in a well defined population are analysed. We report the epidemiology of all HCL patients in Iceland, their clinical characteristics, treatment and follow-up. PATIENTS AND METHODS: : All patients diagnosed with HCL in Iceland over a 20 year period, were included in this study. Data was collected retrospectively. RESULTS: Sixteen patients, 13 males and three females were diagnosed with HCL in Iceland from 1981-2000, giving a mean incidence of 4.7/million/year (95% CI: 2.7-7.6) in the population 20 years and older. Eleven patients were treated with a purine analogue, 10 of whom achieved CR. One other patient obtained CR following splenectomy and IFN, giving a total CR rate of 69%. Three other patients (19%) obtained PR, giving a total response rate of 88%. One patient had a variant of HCL and did not respond to any therapy and one patient died of sepsis before any chemotherapy could be given. Six patients with HCL have died, one from complications of HCL. Three patients developed a second malignancy (19%). CONCLUSIONS: The mean incidence of HCL in Iceland is 4.7/million/year. This is slighty higher than the reported incidence in England and Wales, although not significantly higher. The incidence is based on a nationwide information from a well defined stable and racially homogenous island population. Other results are in accordance with previously published studies.