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Leukemia & Lymphoma Volume 60, 2019 - Issue 7
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Original Article – Research

Genetic polymorphisms in genes of class switch recombination and multiple myeloma risk and survival: an IMMEnSE study

Daniele CampaDepartment of Biology, University of Pisa, Pisa, Italy; View further author information
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Alessandro MartinoGenomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany; View further author information
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Angelica MacaudaDepartment of Biology, University of Pisa, Pisa, Italy; ;Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany; ORCID Iconhttp://orcid.org/0000-0001-9820-5079View further author information
ORCID Icon,
Marek DudzińskiHematology Department, Teaching Hospital No 1, Rzeszów, Poland; View further author information
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Anna SuskaDepartment of Hematology, Jagiellonian University Medical College, Cracow, Poland; View further author information
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Agnieszka Druzd-SitekLymphoma Department, Centre of Oncology-Institute of Maria Skłodowska-Curie, Warsaw, Poland; View further author information
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Marc-Steffen RaabDepartment of Internal Medicine V, Heidelberg University Hospital, Heidelberg, Germany; ;Max-Eder Research Group Experimental Therapies for Hematologic Malignancies, German Cancer Research Center (DKFZ), Heidelberg, Germany; View further author information
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Victor MorenoCancer Prevention and Control Program, Catalan Institute of Oncology (ICO), IDIBELL, CIBERESP and Department of Clinical Sciences, Faculty of Medicine, University of Barcelona, Barcelona, Spain; ORCID Iconhttp://orcid.org/0000-0002-2818-5487View further author information
ORCID Icon,
Stefanie HuhnMolecular Biology Laboratory, Section of Multiple Myeloma, Department of Internal Medicine V, Heidelberg University Hospital, Heidelberg, Germany; View further author information
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Aleksandra ButrymDepartment of Internal and Occupational Diseases, Hypertension and Clinical Oncology, Wroclaw Medical University, Wroclaw, Poland; View further author information
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Juan SainzPTS Granada, Genomic Oncology Area, GENYO. Centre for Genomics and Oncological Research: Pfizer / University of Granada / Andalusian Regional Government, Granada, Spain; ;Monoclonal Gammopathies Unit, University Hospital Virgen de las Nieves, Granada, Spain; ;Pharmacogenetics Unit. Instituto de Investigación Biosanitaria de Granada (Ibs. Granada), Hospitales Universitarios de Granada / Universidad de Granada, Granada, Spain; View further author information
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Gergely SzombathDepartment of Intrenal Medicine, Semmelweis University, Budapest, Hungary; View further author information
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Marcin RymkoDepartment of Haematology, Copernicus Town Hospital of Torun, Torun, Poland; View further author information
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Herlander MarquesLife and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal; View further author information
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Fabienne LesueurINSERM U900, Paris, France; ;Institut Curie, Paris, France; ;Mines ParisTech, Fontainebleau, France; ;PSL University, Paris, France; View further author information
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Annette Juul VangstedDepartment of Hematology, Copenhagen University Hospital, Rigshospitalet, Denmark; View further author information
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Ulla VogelNational Research Centre for the Working Environment, Denmark; View further author information
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Marcin KruszewskiDepartment of Hematology, University Hospital, Bydgoszcz, Poland; View further author information
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Edyta SuboczDepartment of Haematology, Military Institute of Medicine, Warsaw, Poland; View further author information
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Gabriele BudaHematology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy; View further author information
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Elżbieta Iskierka-JażdżewskaDepartment of Hematology, Copernicus Memorial Hospital, Medical University of Lodz, Lodz, Poland; View further author information
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Rafael RíosPTS Granada, Genomic Oncology Area, GENYO. Centre for Genomics and Oncological Research: Pfizer / University of Granada / Andalusian Regional Government, Granada, Spain; ;Monoclonal Gammopathies Unit, University Hospital Virgen de las Nieves, Granada, Spain; ;Pharmacogenetics Unit. Instituto de Investigación Biosanitaria de Granada (Ibs. Granada), Hospitales Universitarios de Granada / Universidad de Granada, Granada, Spain; View further author information
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Maximilian MerzDepartment of Internal Medicine V, Heidelberg University Hospital, Heidelberg, Germany; View further author information
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Ben SchöttkerDivision of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany; ;Network Aging Research (NAR), University of Heidelberg, Heidelberg, Germany; View further author information
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Grzegorz MazurDepartment of Internal and Occupational Diseases, Hypertension and Clinical Oncology, Wroclaw Medical University, Wroclaw, Poland; View further author information
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Emeline PerrialCancer Research Center of Lyon, INSERM 1052/CNRS 5286, University of Lyon, Lyon, France; View further author information
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Joaquin Martinez-LopezHospital 12 de Octubre, Complutense University, CNIO, CIBERONC, Madrid, Spain; ORCID Iconhttp://orcid.org/0000-0001-7908-0063View further author information
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Katja ButterbachNetwork Aging Research (NAR), University of Heidelberg, Heidelberg, Germany; View further author information
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Ramón García SanzDepartment of Hematology, University Hospital of Salamanca, Salamanca, Spain; View further author information
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Hartmut GoldschmidtDepartment of Internal Medicine V, Heidelberg University Hospital, Heidelberg, Germany; ;National Center for Tumor Diseases (NCT), Heidelberg, Germany; View further author information
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Hermann BrennerDivision of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany; ;Network Aging Research (NAR), University of Heidelberg, Heidelberg, Germany; ;Division of Preventive Oncology, National Center for Tumor Diseases (NCT) German Cancer Research Center (DKFZ), Heidelberg, Germany; ;German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany; View further author information
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Krzysztof JamroziakDepartment of Hematology, Institute of Hematology and Transfusion Medicine, Warsaw, Poland; View further author information
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Rui Manuel ReisLife and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal; ;ICVS/3B’s – PT Government Associate Laboratory, Braga/Guimarães, Portugal; ;Barretos Cancer Hospital, Molecular Oncology Research Center, S. Paulo, Brazil; View further author information
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Katalin KadarDepartment of Intrenal Medicine, Semmelweis University, Budapest, Hungary; View further author information
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Charles DumontetCancer Research Center of Lyon, INSERM 1052/CNRS 5286, University of Lyon, Lyon, France; View further author information
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Marzena WątekDepartment of Hematology, Holy Cross Oncology Center, Kielce, Poland; View further author information
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Eva Kannik HaastrupDepartment of Clinical Immunology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark; View further author information
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Grzegorz HelbigDepartment of Hematology and Bone Marrow Transplantation, Medical University of Silesia, Katowice, Poland; View further author information
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Artur JurczyszynDepartment of Hematology, Jagiellonian University Medical College, Cracow, Poland; View further author information
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Andrés JerezDepartment of Hematology, University Hospital Morales Meseguer, IMIB, Murcia, Spain; View further author information
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Judit VarkonyiDepartment of Intrenal Medicine, Semmelweis University, Budapest, Hungary; View further author information
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Torben BaringtonDepartment of Clinical Immunology, Odense University Hospital, Odense, Denmark; ORCID Iconhttp://orcid.org/0000-0001-6968-148XView further author information
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Norbert GrzaskoDepartment of Hematology, St. John’s Cancer Center, Lublin, Poland; ;Department of Experimental Hematooncology, Medical University of Lublin, Lublin, Poland; View further author information
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Jan Maciej ZauchaDepartment of Hematology, Sea Hospital, Gdynia, Poland; View further author information
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Vibeke AndersenIRS-Center Sønderjylland, Aabenraa, Denmark; ;Institute of Molecular Biology, University of Southern Denmark, Odense, Denmark; View further author information
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Daria ZawirskaDepartment of Haematology, University Hospital of Cracow, Cracow, PolandView further author information
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Federico CanzianGenomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany; Correspondence[email protected]
ORCID Iconhttp://orcid.org/0000-0002-4261-4583View further author information
ORCID Icon show all
Pages 1803-1811 | Received 25 Jul 2018, Accepted 14 Nov 2018, Published online: 11 Jan 2019
 
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Abstract

Genetic variants in genes acting during the maturation process of immature B-cell to differentiated plasma cell could influence the risk of developing multiple myeloma (MM). During B-cell maturation, several programmed genetic rearrangements occur to increase the variation of the immunoglobulin chains. Class switch recombination (CSR) is one of the most important among these mechanisms. Germline polymorphisms altering even subtly this process could play a role in the etiology and outcome of MM. We performed an association study of 30 genetic variants in the key CSR genes, using 2632 MM patients and 2848 controls from the International Multiple Myeloma rESEarch (IMMEnSE) consortium, the Heidelberg MM Group and the ESTHER cohort. We found an association between LIG4-rs1555902 and decreased MM risk, which approached statistical significance, as well as significant associations between AICDA-rs3794318 and better outcome. Our results add to our knowledge on the genetic component of MM risk and survival.

Additional information

Funding

This work was partially supported by intramural funds of DKFZ, by grants PI12/02688 and PI17/02276 from Fondo de Investigaciones Sanitarias (Madrid, Spain), Instituto de Salud Carlos III, co-funded by FEDER funds –a way to build Europe– grant PI14-00613 and Agency for Management of University and Research Grants (AGAUR) of the Catalan Government grant 2017SGR723. The ESTHER study was funded by grants from the Baden-Württemberg state Ministry of Science, Research and Arts (Stuttgart, Germany), the Federal Ministry of Education and Research (Berlin, Germany), the Federal Ministry of Family Affairs, Senior Citizens, Women and Youth (Berlin, Germany) and the Saarland Ministry of Social Affairs, Health, Women and Family (Saarbrücken, Germany).

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