A population-based case-control study was conducted to evaluate risk of developing multiple myeloma (MM) associated with personal history of autoimmune diseases and occurrence of autoimmune and selected hematologic disorders in first-degree relatives. Data were obtained for all (n = 8,406) MM cases diagnosed in Sweden (1958-1998), with linkable relatives, 16,543 matched controls and first-degree relatives of cases (n = 22,490) and controls (n = 44,436). Odds ratios (ORs) were calculated to quantify the risk of MM in relation to personal/family history of 32 autoimmune disorders. Familial aggregation of malignancies was evaluated in a marginal survival model using relatives as the cohort. The risk for MM was significantly elevated among subjects with a personal history of pernicious anemia (OR = 3.27; 2.22-4.83) and individuals with a family history of systemic lupus erythematosus (OR = 2.66; 1.12-6.32). Compared with controls, relative risk (RR) of MM was significantly increased (RR = 1.67; 1.02-2.73) in relatives of cases, particularly relatives of probands aged > or =65 at diagnosis (RR = 2.50; 1.19-5.27). Risks were nearly 4-fold elevated among female relatives (RR = 3.97; 1.54-10.2) and among relatives of female probands (RR = 3.74; 1.58-8.83). MM cases had more cases of monoclonal gammopathy of undetermined significance (MGUS) among their relatives than controls, but the numbers were too small to be conclusive. There was generally no increase in risk of MM in probands whose relatives had hematologic malignancies other than MM. These findings do not support a strong association between personal/familial autoimmune diseases and MM. However, MM itself shows significant familial aggregation, implicating the etiologic importance of this type of hematological neoplasm and perhaps MGUS in germ line genes.

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