Identification of miRSNPs associated with the risk of multiple myeloma

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• 作者：Angelica Macauda ; Diego Calvetti ; Giuseppe Maccari ; Kari Hemminki ; Asta F&ouml ; rsti ; 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-Sitek ; Marcin 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 ; Ramó ; n Garcí ; a Sanz ; Charles Dumontet ; Victor Moreno ; Anna Stępień ; Katia Beider ; Matteo Pelosini ; Rui Manuel Reis ; Malgorzata Krawczyk-Kulis ; Marcin Rymko ; Herv&eacute ; Avet-Loiseau ; Fabienne Lesueur ; Norbert Grząśko ; Olga Ostrovsky ; Krzysztof Jamroziak ; Annette J. Vangsted ; Andr&eacute ; s Jerez ; Waldemar Tomczak ; Jan Maciej Zaucha ; Katalin Kadar ; Juan Sainz ; Arnon Nagler ; Stefano Landi ; Federica Gemignani and Federico Canzian
• 刊名：International Journal of Cancer
• 出版年：2017
• 出版时间：1 February 2017
• 年：2017
• 卷：140
• 期：3
• 页码：526-534
• 全文大小：335K
• ISSN：1097-0215

文摘

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 m>in silicom> 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 seven European countries and Israel in the context of the IMMEnSE (International Multiple Myeloma rESEarch) consortium. In this population two SNPs showed an association with m>pm> < 0.05: rs286595 (located in gene m>MRLP22m>) and rs14191881 (located in gene m>TCF19m>). Results from IMMEnSE were meta-analyzed with data from a previously published genome-wide association study (GWAS). The SNPs rs13409 (located in the 3&prime;UTR of the m>POU5F1m> gene), rs1419881 (m>TCF19m>), rs1049633, rs1049623 (both in m>DDR1m>) 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.