Identification of miRSNPs associated with the risk of multiple myeloma

Angelica Macauda, Diego Calvetti, Giuseppe Maccari, Kari Hemminki, Asta Försti, Hartmut Goldschmidt, Niels Weinhold, Richard Houlston, Vibeke Andersen, Ulla Vogel, Gabriele Buda, Judit Varkonyi, Anna Sureda, Joaquin Martinez Lopez, Marzena Watek, Aleksandra Butrym, Maria Eugenia Sarasquete, Marek Dudziński, Artur Jurczyszyn, Agnieszka Druzd-SitekMarcin Kruszewski, Edyta Subocz, Mario Petrini, Elzbieta Iskierka-Jażdżewska, Malgorzata Raźny, Gergely Szombath, Herlander Marques, Daria Zawirska, Dominik Chraniuk, Janusz Halka, Svend Erik Hove Jacobsen, Grzegorz Mazur, Ramón García Sanz, Charles Dumontet, Victor Moreno, Anna Stępień, Katia Beider, Matteo Pelosini, Rui Manuel Reis, Malgorzata Krawczyk-Kulis, Marcin Rymko, Hervé Avet-Loiseau, Fabienne Lesueur, Norbert Grząśko, Olga Ostrovsky, Krzysztof Jamroziak, Annette J Vangsted, Andrés Jerez, Waldemar Tomczak, Jan Maciej Zaucha, Katalin Kadar, Juan Sainz Pérez, Arnon Nagler, Stefano Landi, Federica Gemignani, Federico Canzian

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Abstract

Multiple myeloma (MM) is a malignancy of plasma cells usually infiltrating the bone marrow, associated with the production of a monoclonal immunoglobulin (M protein) which can be detected in the blood and/or urine. Multiple lines of evidence suggest that genetic factors are involved in MM pathogenesis, and several studies have identified single nucleotide polymorphisms (SNPs) associated with the susceptibility to the disease. SNPs within miRNA-binding sites in target genes (miRSNPs) may alter the strength of miRNA-mRNA interactions, thus deregulating protein expression. MiRSNPs are known to be associated with risk of various types of cancer, but they have never been investigated in MM. We performed an in silico genome-wide search for miRSNPs predicted to alter binding of miRNAs to their target sequences. We selected 12 miRSNPs and tested their association with MM risk. Our study population consisted of 1,832 controls and 2,894 MM cases recruited from 7 European countries and Israel in the context of the IMMEnSE (International Multiple Myeloma rESEarch) consortium. In this population two SNPs showed an association with p<0.05: rs286595 (located in gene MRLP22) and rs14191881 (located in gene TCF19). Results from IMMEnSE were meta-analyzed with data from a previously published genome-wide association study (GWAS). The SNPs rs13409 (located in the 3'UTR of the POU5F1 gene), rs1419881 (TCF19), rs1049633, rs1049623 (both in DDR1) showed significant associations with MM risk. In conclusion, we sought to identify genetic polymorphisms associated with MM risk starting from genome-wide prediction of miRSNPs. For some mirSNPs we have shown promising associations with MM risk. This article is protected by copyright. All rights reserved.

Original languageEnglish
JournalInternational Journal of Cancer
Volume140
Issue number3
Pages (from-to)526-534
ISSN0020-7136
DOIs
Publication statusPublished - 2017

Keywords

  • Genetic susceptibility
  • Multiple myeloma
  • SNP
  • miRNA
  • 3' Untranslated Regions/genetics
  • MicroRNAs/genetics
  • Multiple Myeloma/genetics
  • Europe
  • Humans
  • Middle Aged
  • Genetic Predisposition to Disease/genetics
  • Genotype
  • Male
  • Risk
  • Binding Sites/genetics
  • Case-Control Studies
  • RNA, Messenger/genetics
  • Polymorphism, Single Nucleotide/genetics
  • Myeloma Proteins/genetics
  • Genome-Wide Association Study/methods
  • Adult
  • Female
  • Aged

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  • Cite this

    Macauda, A., Calvetti, D., Maccari, G., Hemminki, K., Försti, A., Goldschmidt, H., Weinhold, N., Houlston, R., Andersen, V., Vogel, U., Buda, G., Varkonyi, J., Sureda, A., Lopez, J. M., Watek, M., Butrym, A., Sarasquete, M. E., Dudziński, M., Jurczyszyn, A., ... Canzian, F. (2017). Identification of miRSNPs associated with the risk of multiple myeloma. International Journal of Cancer, 140(3), 526-534. https://doi.org/10.1002/ijc.30465