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Multiple myeloma gammopathies

Genetic predisposition for multiple myeloma

Leukemia volume 34, pages 697–708 (2020)Cite this article

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Abstract

Multiple myeloma (MM) is the second most common blood malignancy. Epidemiological family studies going back to the 1920s have provided evidence for familial aggregation, suggesting a subset of cases have an inherited genetic background. Recently, studies aimed at explaining this phenomenon have begun to provide direct evidence for genetic predisposition to MM. Genome-wide association studies have identified common risk alleles at 24 independent loci. Sequencing studies of familial cases and kindreds have begun to identify promising candidate genes where variants with strong effects on MM risk might reside. Finally, functional studies are starting to give insight into how identified risk alleles promote the development of MM. Here, we review recent findings in MM predisposition field, and highlight open questions and future directions.

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Fig. 1: Genomic location of MM risk alleles identified in genome-wide association studies.

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Acknowledgements

The authors were supported by Knut and Alice Wallenberg’s Foundation (2012.0193 and 2017.0436), the Swedish Research Council (2018-00424), the Swedish Cancer Society (2017/265), the Nordic Cancer Union (R217-A13329), and the Stiftelsen Borås forsknings- och utvecklingsfond mot cancer. RSH is supported by BLOODWISE and MYELOMA UK.

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Authors and Affiliations

  1. Hematology and Transfusion Medicine, Department of Laboratory Medicine, BMC B13, 221 84, Lund, Sweden

    Maroulio Pertesi, Markus Hansson & Björn Nilsson

  2. Division of Genetics and Epidemiology, The Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey, SM2 5NG, UK

    Molly Went & Richard S. Houlston

  3. Department of Cancer Epidemiology, German Cancer Research Center, Im Neuenheimer Feld, Heidelberg, Germany

    Kari Hemminki

  4. Faculty of Medicine and Biomedical Center, Charles University in Prague, 30605, Pilsen, Czech Republic

    Kari Hemminki

  5. Broad Institute, 415 Main Street, Cambridge, MA, 02142, USA

    Björn Nilsson

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Pertesi, M., Went, M., Hansson, M. et al. Genetic predisposition for multiple myeloma. Leukemia 34, 697–708 (2020). https://doi.org/10.1038/s41375-019-0703-6

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