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Research Papers:

A common variant within the HNF1B gene is associated with overall survival of multiple myeloma patients: results from the IMMEnSE consortium and meta-analysis

Rafael Ríos-Tamayo, Carmen Belén Lupiañez, Daniele Campa, Thomas Hielscher, Niels Weinhold, Joaquin Martínez-López, Andrés Jerez, Stefano Landi, Krzysztof Jamroziak, Charles Dumontet, Marzena Wątek, Fabienne Lesueur, Rui Manuel Reis, Herlander Marques, Artur Jurczyszyn, Ulla Vogel, Gabriele Buda, Ramón García-Sanz, Enrico Orciuolo, Mario Petrini, Annette J. Vangsted, Federica Gemignani, Asta Försti, Hartmut Goldschmidt, Kari Hemminki, Federico Canzian, Manuel Jurado and Juan Sainz _

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Oncotarget. 2016; 7:59029-59048. https://doi.org/10.18632/oncotarget.10665

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Abstract

Rafael Ríos-Tamayo1,2,*, Carmen Belén Lupiañez1,2,*, Daniele Campa3, Thomas Hielscher4, Niels Weinhold5,6, Joaquin Martínez-López7, Andrés Jerez8, Stefano Landi3, Krzysztof Jamroziak9, Charles Dumontet10, Marzena Wątek11, Fabienne Lesueur12,13,14,15, Rui Manuel Reis16,17,18, Herlander Marques16,17, Artur Jurczyszyn19, Ulla Vogel20, Gabriele Buda21, Ramón García-Sanz22, Enrico Orciuolo21, Mario Petrini21, Annette J. Vangsted23, Federica Gemignani3, Asta Försti24, Hartmut Goldschmidt6,25, Kari Hemminki24, Federico Canzian26, Manuel Jurado1,2, Juan Sainz1,2

1Genomic Oncology Area, Pfizer-University of Granada-Junta de Andalucía Centre for Genomics and Oncological Research (GENYO), Granada, Spain

2Hematology Department, Virgen de las Nieves University Hospital, Granada, Spain

3Department of Biology, University of Pisa, Pisa, Italy

4Division of Biostatistics, German Cancer Research Center (DKFZ), Heidelberg, Germany

5Myeloma Institute, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA

6Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany

7Department of Hematology, Hospital Universitario Doce de Octubre, Madrid, Spain

8Hematology and Medical Oncology Department, University Hospital Morales Meseguer, IMIB, Murcia, Spain

9Medical University of Lodz, Lodz, Poland

10INSERM UMR 1052/CNRS 5286, Universite Claude Bernard Lyon I, Lyon, France

11Hematoloy Clinik, Holy Cross Cancer Center, Kielce, Poland

12Institute Curie, Paris, France

13PSL Research University, Paris, France

14INSERM, U900, Paris, France

15Mines ParisTech, F-77305 Cedex Fontainebleau, France

16Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal

17ICVS/3B’s – PT Government Associate Laboratory, Braga/Guimarães, Portugal

18Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, Brazil

19Jagiellonian University Medical College, Department of Haematology, Kraków, Poland

20National Research Centre for the Working Environment, Copenhagen, Denmark

21UO Hematology, Department of Internal and Experimental Medicine, University of Pisa, Pisa, Italy

22Haematology Department, University Hospital of Salamanca & IBSAL, Salamanca, Spain

23Department of Hematology, Rigshospitalet, Copenhagen, Denmark

24Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany

25National Center of Tumor Diseases, Heidelberg, Germany

26Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany

*These authors contributed equally to this work

Correspondence to:

Juan Sainz, email: juan.sainz@genyo.es

Keywords: multiple myeloma, diabetes, genetic variants, survival

Received: April 07, 2016     Accepted: May 19, 2016     Published: July 18, 2016

ABSTRACT

Diabetogenic single nucleotide polymorphisms (SNPs) have recently been associated with multiple myeloma (MM) risk but their impact on overall survival (OS) of MM patients has not been analysed yet. In order to investigate the impact of 58 GWAS-identified variants for type 2 diabetes (T2D) on OS of patients with MM, we analysed genotyping data of 936 MM patients collected by the International Multiple Myeloma rESEarch (IMMENSE) consortium and an independent set of 700 MM patients recruited by the University Clinic of Heidelberg. A meta-analysis of the cox regression results of the two sets showed that rs7501939 located in the HNF1B gene negatively impacted OS (HRRec= 1.44, 95% CI = 1.18–1.76, P = 0.0001). The meta-analysis also showed a noteworthy gender-specific association of the SLC30A8rs13266634 SNP with OS. The presence of each additional copy of the minor allele at rs13266634 was associated with poor OS in men whereas no association was seen in women (HRMen-Add = 1.32, 95% CI 1.13–1.54, P = 0.0003). In conclusion, these data suggest that the HNF1Brs7501939 SNP confers poor OS in patients with MM and that a SNP in SLC30A8 affect OS in men.


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