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-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; 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; Arnon Nagler; Stefano Landi; Federica Gemignani; Federico Canzian

doi:10.1002/ijc.30465

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, Arnon Nagler, Stefano Landi, Federica Gemignani, Federico Canzian

Department of Clinical Medicine

6 Citations (Scopus)

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.

Original language	English
Journal	International Journal of Cancer
Volume	140
Issue number	3
Pages (from-to)	526-534
Number of pages	9
ISSN	0020-7136
DOIs	https://doi.org/10.1002/ijc.30465
Publication status	Published - 1 Feb 2017

Keywords

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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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., Martinez Lopez, J., 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

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, Martinez Lopez, J, Watek, M, Butrym, A, Sarasquete, ME, Dudziński, M, Jurczyszyn, A, Druzd-Sitek, A, Kruszewski, M, Subocz, E, Petrini, M, Iskierka-Jażdżewska, E, Raźny, M, Szombath, G, Marques, H, Zawirska, D, Chraniuk, D, Halka, J, Hove Jacobsen, SE, Mazur, G, García Sanz, R, Dumontet, C, Moreno, V, Stępień, A, Beider, K, Pelosini, M, Manuel Reis, R, Krawczyk-Kulis, M, Rymko, M, Avet-Loiseau, H, Lesueur, F, Grząśko, N, Ostrovsky, O, Jamroziak, K, Vangsted, AJ, Jerez, A, Tomczak, W, Zaucha, JM, Kadar, K, Sainz, J, Nagler, A, Landi, S, Gemignani, F & Canzian, F 2017, 'Identification of miRSNPs associated with the risk of multiple myeloma', International Journal of Cancer, vol. 140, no. 3, pp. 526-534. https://doi.org/10.1002/ijc.30465

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title = "Identification of miRSNPs associated with the risk of multiple myeloma",

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.",

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author = "Angelica Macauda and Diego Calvetti and Giuseppe Maccari and Kari Hemminki and Asta F{\"o}rsti and Hartmut Goldschmidt and Niels Weinhold and Richard Houlston and Vibeke Andersen and Ulla Vogel and Gabriele Buda and Judit Varkonyi and Anna Sureda and {Martinez Lopez}, Joaquin and Marzena Watek and Aleksandra Butrym and Sarasquete, {Maria Eugenia} and Marek Dudzi{\'n}ski and Artur Jurczyszyn and Agnieszka Druzd-Sitek and Marcin Kruszewski and Edyta Subocz and Mario Petrini and Elzbieta Iskierka-Ja{\.z}d{\.z}ewska and Malgorzata Ra{\'z}ny and Gergely Szombath and Herlander Marques and Daria Zawirska and Dominik Chraniuk and Janusz Halka and {Hove Jacobsen}, {Svend Erik} and Grzegorz Mazur and {Garc{\'i}a Sanz}, Ram{\'o}n and Charles Dumontet and Victor Moreno and Anna St{\c e}pie{\'n} and Katia Beider and Matteo Pelosini and {Manuel Reis}, Rui and Malgorzata Krawczyk-Kulis and Marcin Rymko and Herv{\'e} Avet-Loiseau and Fabienne Lesueur and Norbert Grz{\c a}{\'s}ko and Olga Ostrovsky and Krzysztof Jamroziak and Vangsted, {Annette J} and Andr{\'e}s Jerez and Waldemar Tomczak and Zaucha, {Jan Maciej} and Katalin Kadar and Juan Sainz and Arnon Nagler and Stefano Landi and Federica Gemignani and Federico Canzian",

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day = "1",

doi = "10.1002/ijc.30465",

language = "English",

volume = "140",

pages = "526--534",

journal = "International Journal of Cancer",

issn = "0020-7136",

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TY - JOUR

T1 - Identification of miRSNPs associated with the risk of multiple myeloma

AU - Macauda, Angelica

AU - Calvetti, Diego

AU - Maccari, Giuseppe

AU - Hemminki, Kari

AU - Försti, Asta

AU - Goldschmidt, Hartmut

AU - Weinhold, Niels

AU - Houlston, Richard

AU - Andersen, Vibeke

AU - Vogel, Ulla

AU - Buda, Gabriele

AU - Varkonyi, Judit

AU - Sureda, Anna

AU - Martinez Lopez, Joaquin

AU - Watek, Marzena

AU - Butrym, Aleksandra

AU - Sarasquete, Maria Eugenia

AU - Dudziński, Marek

AU - Jurczyszyn, Artur

AU - Druzd-Sitek, Agnieszka

AU - Kruszewski, Marcin

AU - Subocz, Edyta

AU - Petrini, Mario

AU - Iskierka-Jażdżewska, Elzbieta

AU - Raźny, Malgorzata

AU - Szombath, Gergely

AU - Marques, Herlander

AU - Zawirska, Daria

AU - Chraniuk, Dominik

AU - Halka, Janusz

AU - Hove Jacobsen, Svend Erik

AU - Mazur, Grzegorz

AU - García Sanz, Ramón

AU - Dumontet, Charles

AU - Moreno, Victor

AU - Stępień, Anna

AU - Beider, Katia

AU - Pelosini, Matteo

AU - Manuel Reis, Rui

AU - Krawczyk-Kulis, Malgorzata

AU - Rymko, Marcin

AU - Avet-Loiseau, Hervé

AU - Lesueur, Fabienne

AU - Grząśko, Norbert

AU - Ostrovsky, Olga

AU - Jamroziak, Krzysztof

AU - Vangsted, Annette J

AU - Jerez, Andrés

AU - Tomczak, Waldemar

AU - Zaucha, Jan Maciej

AU - Kadar, Katalin

AU - Sainz, Juan

AU - Nagler, Arnon

AU - Landi, Stefano

AU - Gemignani, Federica

AU - Canzian, Federico

PY - 2017/2/1

Y1 - 2017/2/1

N2 - 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.

AB - 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.

KW - 3' Untranslated Regions/genetics

KW - Adult

KW - Aged

KW - Binding Sites/genetics

KW - Case-Control Studies

KW - Europe

KW - Female

KW - Genetic Predisposition to Disease/genetics

KW - Genome-Wide Association Study/methods

KW - Genotype

KW - Humans

KW - Male

KW - MicroRNAs/genetics

KW - Middle Aged

KW - Multiple Myeloma/genetics

KW - Myeloma Proteins/genetics

KW - Polymorphism, Single Nucleotide/genetics

KW - RNA, Messenger/genetics

KW - Risk

U2 - 10.1002/ijc.30465

DO - 10.1002/ijc.30465

M3 - Journal article

C2 - 27718532

SN - 0020-7136

VL - 140

SP - 526

EP - 534

JO - International Journal of Cancer

JF - International Journal of Cancer

IS - 3

ER -

Identification of miRSNPs associated with the risk of multiple myeloma

Abstract

Keywords

UN SDGs

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