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Genetic factors influencing the risk of multiple myeloma bone disease

Lookup NU author(s): Professor Graham Jackson

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

A major complication of multiple myeloma (MM) is the development of osteolytic lesions, fractures and bone pain. To identify genetic variants influencing the development of MM bone disease (MBD), we analyzed MM patients of European ancestry (totaling 3774), which had been radiologically surveyed for MBD. Each patient had been genotyped for similar to 6 00 000 single-nucleotide polymorphisms with genotypes for six million common variants imputed using 1000 Genomes Project and UK10K as reference. We identified a locus at 8q24.12 for MBD (rs4407910, OPG/TNFRSF11B, odds ratio = 1.38, P = 4.09 x 10(-9)) and a promising association at 19q13.43 (rs74676832, odds ratio = 1.97, P = 9.33 x 10(-7)). Our findings demonstrate that germline variation influences MBD and highlights the importance of RANK/RANKL/OPG pathway in MBD development. These findings will contribute to the development of future strategies for prevention of MBD in the early precancerous phases of MM.


Publication metadata

Author(s): Johnson DC, Weinhold N, Mitchell J, Chen B, Stephens OW, Forsti A, Nickel J, Kaiser M, Gregory WA, Cairns D, Jackson GH, Hoffmann P, Noethen MM, Hillengass J, Bertsch U, Barlogie B, Davis FE, Hemminki K, Goldschmidt H, Houlston RS, Morgan GJ

Publication type: Article

Publication status: Published

Journal: Leukemia

Year: 2016

Volume: 30

Issue: 4

Pages: 883-888

Print publication date: 01/04/2016

Online publication date: 12/01/2016

Acceptance date: 30/11/2015

Date deposited: 14/06/2016

ISSN (print): 0887-6924

ISSN (electronic): 1476-5551

Publisher: Nature Publishing Group

URL: http://dx.doi.org/10.1038/leu.2015.342

DOI: 10.1038/leu.2015.342


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Funding

Funder referenceFunder name
NHS via the Biological Research Centre of the National Institute for Health Research at the Royal Marsden Hospital NHS Trust
Leukaemia Lymphoma Research
Myeloma UK
01ZX1309BGerman Ministry of Education and Science (Cliommics)
C1298/A8362Cancer Research UK (Bobby Moore Fund)
ER 155/6-1German Research Council (DFG)
P01CA055819National Institutes of Health
SI 236/8-1German Research Council (DFG)
SI236/9-1German Research Council (DFG)

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