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Multiple myeloma gammopathies

Eight novel loci implicate shared genetic etiology in multiple myeloma, AL amyloidosis, and monoclonal gammopathy of unknown significance

Leukemia volume 34, pages 1187–1191 (2020)Cite this article

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Multiple myeloma (MM) is caused by a clonal proliferation of malignant plasma cells in the bone marrow preceded by monoclonal gammopathy of unknown significance (MGUS) [1]. This indolent stage can also progress to immunoglobulin light chain amyloidosis (AL amyloidosis) characterized by deposition of free light chains in multiple organs [2].

Genome-wide association studies (GWASs) have identified 23 risk loci for MM [3]. Six of these were associated with AL amyloidosis at a significance level of P < 1.0 × 10−5 and additionally four single nucleotide polymorphisms (SNPs), unrelated to MM reached that significance level [4]. A recent meta-analysis found eight MGUS-specific loci and two loci shared between MGUS and MM reaching a meta-analyzed P value below 1.0 × 10−5 [5]. In addition, ten of the reported MM risk loci were at least weakly associated with MGUS. Collectively these data are consistent with a common heritable basis and comparison of the three plasma cell dyscrasias may discern signals that are related to all three. To explore this possibility we analyzed European GWAS data on MM, AL amyloidosis, and MGUS.

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Acknowledgements

This work is supported by Multiple Myeloma Research Foundation, the German Ministry of Education and Science (01ZX1309B), the Harald Huppert Foundation, Dietmar Hopp Stiftung and Deutsche Krebshilfe. Research by the Houlston group is supported by grants from Myeloma UK and BLOODWISE. PV and LV are recipients of a support from UNCE-MED006 and PROGRESS Q28.

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Authors and Affiliations

  1. Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 580, D-69120, Heidelberg, Germany

    Subhayan Chattopadhyay, Hauke Thomsen, Iman Meziane, Miguel Inacio da Silva Filho, Kari Hemminki & Asta Försti

  2. Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 580, D-69120, Heidelberg, Germany

    Subhayan Chattopadhyay & Kari Hemminki

  3. Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany

    Niels Weinhold, Stefanie Huhn, Ute Hegenbart, Stefan O. Schönland & Hartmut Goldschmidt

  4. Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Videnska 1083, 142 00, Prague, Czech Republic

    Pavel Vodicka & Ludmila Vodickova

  5. Institute of Biology and Medical Genetics, 1st Medical Faculty, Charles University, Albertov 4, 128 00, Prague, Czech Republic

    Pavel Vodicka & Ludmila Vodickova

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

    Pavel Vodicka, Ludmila Vodickova & Kari Hemminki

  7. Institute of Human Genetics, University of Bonn, Bonn, Germany

    Per Hoffmann & Markus M. Nöthen

  8. Department of Biomedicine, University of Basel, Basel, Switzerland

    Per Hoffmann

  9. Department of Genomics, Life & Brain Research Center, University of Bonn, Bonn, Germany

    Markus M. Nöthen

  10. Institute for Medical Informatics, Biometry and Epidemiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany

    Karl-Heinz Jöckel & Börge Schmidt

  11. Department of Biology, University of Pisa, Pisa, Italy

    Stefano Landi

  12. Department of Hematooncology, University Hospital Ostrava, 17. listopadu 1790, 708 52, Ostrava, Czech Republic

    Roman Hajek

  13. Department of Medical Biosciences/Pathology, University of Umea, Umea, Sweden

    Göran Hallmans

  14. Clinical Pharmacology, Department of Pharmacology and Clinical Neuroscience, Umea University, Umea, Sweden

    Ulrika Pettersson-Kymmer

  15. Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

    Claes Ohlsson

  16. Amyloidosis Research and Treatment Center, Foundation “Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico San Matteo” and Department of Molecular Medicine, University of Pavia, Pavia, Italy

    Paolo Milani, Giampaolo Merlini & Giovanni Palladini

  17. National Amyloidosis Centre, University College London Medical School, Royal Free Hospital Campus, London, Rowland Hill Street, London, NW32PF, UK

    Dorota Rowcieno, Philip Hawkins & Ashutosh Wechalekar

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

    Richard Houlston

  19. Division of Molecular Patholog, The Institute of Cancer Research, 15 Cotswold Road, Sutton, London, SM2 5NG, UK

    Richard Houlston

  20. National Centre of Tumor Diseases, Heidelberg, Germany

    Hartmut Goldschmidt

  21. Hopp Children’s Cancer Center (KiTZ), Heidelberg, Germany

    Asta Försti

  22. Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), Heidelberg, Germany

    Asta Försti

Authors
  1. Subhayan Chattopadhyay
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  2. Hauke Thomsen
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  4. Iman Meziane
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  9. Per Hoffmann
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  11. Karl-Heinz Jöckel
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  12. Börge Schmidt
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  13. Stefano Landi
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  14. Roman Hajek
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  15. Göran Hallmans
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  17. Claes Ohlsson
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  18. Paolo Milani
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  19. Giampaolo Merlini
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  20. Dorota Rowcieno
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  21. Philip Hawkins
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  22. Ute Hegenbart
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  23. Giovanni Palladini
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  24. Ashutosh Wechalekar
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  25. Stefan O. Schönland
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  26. Richard Houlston
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  27. Hartmut Goldschmidt
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  28. Kari Hemminki
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  29. Asta Försti
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Correspondence to Asta Försti.

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Shared senior authorship: Kari Hemminki and Asta Försti

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Chattopadhyay, S., Thomsen, H., Weinhold, N. et al. Eight novel loci implicate shared genetic etiology in multiple myeloma, AL amyloidosis, and monoclonal gammopathy of unknown significance. Leukemia 34, 1187–1191 (2020). https://doi.org/10.1038/s41375-019-0619-1

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