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Single-nucleotide polymorphism rs1052501 associated with monoclonal gammopathy of undetermined significance and multiple myeloma

Leukemia volume 27, pages 515–516 (2013)Cite this article

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Monoclonal gammopathy of undetermined significance (MGUS) is the most prevalent clonal plasma cell proliferative disorder, present in over 3% of the population aged 50 years and older, with a rate of progression to malignancy of 1% per year.1 MGUS has been shown to precede multiple myeloma (MM) in almost all cases.2 We, and others, have shown evidence for a familial component to MGUS, with first-degree relatives of MM or MGUS probands having a 2.5-fold increased risk of MGUS, indicative of an underlying genetic predisposition.3, 4

While several genetic variants have been identified for MM, none have been identified that are associated with MGUS.5 Broderick et al.6 recently conducted the first genome-wide association study of MM using case–control studies from the United Kingdom and Germany and identified three novel loci at 3p22.1 (rs1052501 in ULK4), 7p15.3 (rs4487645) and 2p23.3 (rs6746082) associated with risk of MM, although the latter did not reach genome-wide significance (P<5 × 10−8). We investigate whether these three loci for MM risk are also associated with risk of MGUS in order to provide evidence that genetic variation influences MM through MGUS. We also attempt to replicate the association of these loci with MM within a case–control study of MM.

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Acknowledgements

This work was supported, in part, by the National Cancer Institute, National Institutes of Health, Bethesda, MD (CA107476, CA100707, CA 83724, and CA92153) and by the NIH/NCRR CTSA Grant Number TL1 RR024152. This work was also supported, in part, by the Jabbs Foundation, Birmingham, United Kingdom and the Henry J Predolin Foundation, USA. This project was supported by NIH/NCRR/NCATS CTSA Grant Number UL1 RR024150. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH.

AUTHOR CONTRIBUTIONS

SLS and CMV conceived of the study question and were responsible for study design and overseeing the project. CMV, SLS and AJG wrote the paper with comments from all coauthors; JRC, ML, CMV, SVR and RAK contributed study populations, and interpreted study findings; DJS, SKM, DRL, CLC performed all statistical analyses and contributed to their interpretation; ADN, AML and RBD provided scientific input and interpretation of analyses; all coauthors read and approved the paper.

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Author notes

  1. S L Slager and C M Vachon: Joint senior authors.

Authors and Affiliations

  1. Department of Health Sciences Research, Division of Epidemiology, College of Medicine, Mayo Clinic, Rochester, MN, USA

    A J Greenberg, J R Cerhan & C M Vachon

  2. Department of Molecular Pharmacology and Experimental Therapeutics, College of Medicine, Mayo Clinic, Rochester, MN, USA

    A M Lee & R B Diasio

  3. Department of Health Sciences Research, Division of Biomedical Statistics and Informatics, College of Medicine, Mayo Clinic, Rochester, MN, USA

    D J Serie, S K McDonnell, D R Larson, C L Colby, A D Norman & S L Slager

  4. Department of Internal Medicine,College of Medicine, Division of General Internal Medicine, Mayo Clinic, Rochester, MN, USA

    M Liebow

  5. Department of Internal Medicine,College of Medicine, Division of Hematology, Mayo Clinic, Rochester, MN, USA

    R A Kyle, S Kumar & S V Rajkumar

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  1. A J Greenberg
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  2. A M Lee
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  6. M Liebow
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  7. D R Larson
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  10. R A Kyle
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  11. S Kumar
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  12. S V Rajkumar
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  15. C M Vachon
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Corresponding author

Correspondence to C M Vachon.

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Greenberg, A., Lee, A., Serie, D. et al. Single-nucleotide polymorphism rs1052501 associated with monoclonal gammopathy of undetermined significance and multiple myeloma. Leukemia 27, 515–516 (2013). https://doi.org/10.1038/leu.2012.232

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