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Familial associations of monoclonal gammopathy of unknown significance with autoimmune diseases

Leukemia volume 30, pages 1766–1769 (2016)Cite this article

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Monoclonal gammopathy of undetermined significance (MGUS) is an asymptomatic premalignant clonal condition, which is diagnosed often fortuitously, through high levels of immunoglobulin-derived serum M-protein produced by a plasma cell clone.1, 2 The prevalence of MGUS increases with age, and in predominantly white populations, it increases from 3% at age 60 years to 9% at age 80–89 years.3 MGUS is a precursor condition for multiple myeloma (MM) and light chain amyloidosis, which are progressive conditions with a fatal outcome. Both MGUS and MM show familial clustering among and between these diseases, suggesting that they share genetic susceptibility; MGUS is also related to some other malignancies of the B-cell lineage.4, 5, 6, 7 Known nongenetic risk factors of MGUS include prior infections and exposure to herbicides.8, 9, 10 Studies on the association of MGUS with personal or familial autoimmune diseases (ADs) have shown several associations for personal history, whereas for family history of combined ADs, the risk of 1.1 was reported.9, 11 For MM, both personal and family histories with certain ADs have been identified.9, 11, 12 However, the risk for MM has been overall small (1.1), and found only in ankylosing spondylitis and systemic sclerosis patients.12

For the present study, we identified 12 140 MGUS patients from Swedish nationwide hospital records, and from the same sources, we identified 769 991 patients with any of 43 ADs. Combining these into a nationwide family register, we provide familial risk for MGUS patients whose first-degree relatives were diagnosed with ADs. Conversely, we also calculated risks for AD patients whose family members were diagnosed with MGUS to yield a largely independent risk estimate. Because of large sex-preference among ADs, sex-specific familial risks were also shown.

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Acknowledgements

Supported by the Multiple Myeloma Research Foundation, the German Ministry of Education and Science (01ZX1309B), and Deutsche Krebshilfe.

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Authors and Affiliations

  1. Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany

    K Hemminki & A Försti

  2. Center for Primary Health Care Research, Lund University, Malmö, Sweden

    K Hemminki, A Försti, K Sundquist, J Sundquist & X Li

  3. Stanford Prevention Research Center, Stanford University School of Medicine, Stanford, CA, USA

    K Sundquist & J Sundquist

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  1. K Hemminki
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Correspondence to K Hemminki.

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Hemminki, K., Försti, A., Sundquist, K. et al. Familial associations of monoclonal gammopathy of unknown significance with autoimmune diseases. Leukemia 30, 1766–1769 (2016). https://doi.org/10.1038/leu.2016.43

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