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Int J Cancer. 2017 Feb 1;140(3):526-534. doi: 10.1002/ijc.30465. Epub 2016 Nov 9.

Identification of miRSNPs associated with the risk of multiple myeloma.

Author information

1
Department of Biology, University of Pisa, Pisa, Italy.
2
Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.
3
The Pirbright Institute, Pirbright, Woking, Surrey, GU24 0NF, United Kingdom.
4
Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
5
Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany.
6
Division of Genetics and Epidemiology, The Institute of Cancer Research, London, United Kingdom.
7
Institute of Regional Health Research, and Institute of Molecular Medicine, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark.
8
Research Unit of Molecular Diagnostics and Clinical Research, Laboratory Center, Hospital of Southern Jutland, Aabenraa, Denmark.
9
National Research Centre for the Working Environment, Copenhagen, DK-2100, Denmark.
10
UO Hematology, Department of Internal and Experimental Medicine, University of Pisa, Pisa, Italy.
11
Department of Hematology, Semmelweis University, Budapest, Hungary.
12
Department of Hematology, Catalan Institute of Oncology (ICO) and IDIBELL, Barcelona, Spain.
13
Department of Hematology, Hospital Universitario 12 de Octubre, Complutense School of Medicine, CNIO, Madrid, Spain.
14
Holycross Medical Center, Kielce, Poland.
15
Medical University, Wrocław, Poland.
16
Department of Hematology, University Hospital of Salamanca, Salamanca, Spain.
17
Department of Hematology, Specialist District Hospital, Rzeszow, Poland.
18
Department of Hematology, Cracow University Hospital, Cracow, Poland.
19
Department of Lymphoid Malignancies Maria Sklodowska-Curie Memorial Institute and Oncology Centre Warsaw, Warsaw, Poland.
20
Department of Hematology, University Hospital, Bydgoszcz, Poland.
21
Department of Hematology, Military Institute of Medicine, Warsaw, Poland.
22
Department of Hematology, Medical University of Lodz, Łódź, Poland.
23
Department of Hematology, Rydygier Hospital, Cracow, Poland.
24
Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal.
25
ICVS/3B's-PT Government Associate Laboratory, Braga, Portugal.
26
Department of Hematology, Copernicus Hospital, Torun, Poland.
27
Clinic of Immunology, Laboratory Center, Hospital of Southern Jutland, Sønderborg, Denmark.
28
Department of Internal Diseases, Hypertension and Occupational Medicine, Medical University, Wroclaw, Poland.
29
INSERM UMR 1052/CNRS 5286, Université Claude Bernard Lyon I, Lyon, 69622, France.
30
Cancer Prevention and Control Program, Catalan Institute of Oncology (ICO), IDIBELL, CIBERESP and Department of Clinical Sciences, Faculty of Medicine, University of Barcelona, Barcelona, Spain.
31
Laboratory of Clinical and Transplant Immunology and Genetics, Copernicus Memorial Hospital, Łódź, Poland.
32
Chaim Sheba Medical Center, Tel-Hashomer, Ramat Gan, Israel.
33
Azienda USL Toscana Nord Ovest, U.O Dipartimento di Ematologia, Livorno, Italy.
34
Barretos Cancer Hospital, Molecular Oncology Research Center, Barretos, Brazil.
35
Department of Hematology and Bone marrow Transplantation, Silesian Medical University, Katowice, Poland.
36
Laboratoire d'hématologie, Pôle biologie, Institut Universitaire du Cancer de Toulouse-Oncopole 1, Avenue Irène Joliot-Curie, Toulouse 31059, France.
37
Institut Curie, 26 rue d'Ulm, Paris, F-75005, France.
38
PSL Research University, Paris, F-75005, France.
39
Inserm, U900, Paris, F-75005, France.
40
Mines Paris Tech, Fontainebleau, Paris, F-77305, France.
41
Department of Hematology, St. John's Cancer Center, Lublin, Poland.
42
Department of Hematology, Institute of Hematology and Transfusion Medicine, Warsaw, Poland.
43
Department of Haematology, Rigshospitalet, Copenhagen University, Copenhagen, Denmark.
44
Department of Hematology and Medical Oncology, IMIB, University Hospital Morales Meseguer, Murcia, Spain.
45
Department of Hematooncology and Bone Marrow Transplantation, Medical University of Lublin, Lublin, Poland.
46
Department of Hematology, Sea Hospital, Gdynia, Poland.
47
Centro Pfizer, Universidad de Granada, Junta de Andalucía de Genómica e Investigación Oncológica (GENYO), Granada, Spain.

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 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 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.

KEYWORDS:

Genetic susceptibility; Multiple myeloma; SNP; miRNA

PMID:
27718532
DOI:
10.1002/ijc.30465
[Indexed for MEDLINE]
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