Meta-Analysis

. 2016 Sep 13;7(37):59029-59048.

doi: 10.18632/oncotarget.10665.

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^{1

2}, Carmen Belén Lupiañez^{1

2}, Daniele Campa³, Thomas Hielscher⁴, Niels Weinhold^{5

6}, Joaquin Martínez-López⁷, Andrés Jerez⁸, Stefano Landi³, Krzysztof Jamroziak⁹, Charles Dumontet¹⁰, Marzena Wątek¹¹, Fabienne Lesueur^{12

13

14

15}, Rui Manuel Reis^{16

17

18}, Herlander Marques^{16

17}, Artur Jurczyszyn¹⁹, Ulla Vogel²⁰, Gabriele Buda²¹, Ramón García-Sanz²², Enrico Orciuolo²¹, Mario Petrini²¹, Annette J Vangsted²³, Federica Gemignani³, Asta Försti²⁴, Hartmut Goldschmidt^{6

25}, Kari Hemminki²⁴, Federico Canzian¹⁰, Manuel Jurado^{1

2}, Juan Sainz^{1

2}

Affiliations

¹ Genomic Oncology Area, Pfizer-University of Granada-Junta de Andalucía Centre for Genomics and Oncological Research (GENYO), Granada, Spain.
² Hematology Department, Virgen de las Nieves University Hospital, Granada, Spain.
³ Department of Biology, University of Pisa, Pisa, Italy.
⁴ Division of Biostatistics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
⁵ Myeloma Institute, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
⁶ Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany.
⁷ Department of Hematology, Hospital Universitario Doce de Octubre, Madrid, Spain.
⁸ Hematology and Medical Oncology Department, University Hospital Morales Meseguer, IMIB, Murcia, Spain.
⁹ Medical University of Lodz, Lodz, Poland.
¹⁰ INSERM UMR 1052/CNRS 5286, Universite Claude Bernard Lyon I, Lyon, France.
¹¹ Hematoloy Clinik, Holy Cross Cancer Center, Kielce, Poland.
¹² Institute Curie, Paris, France.
¹³ PSL Research University, Paris, France.
¹⁴ INSERM, U900, Paris, France.
¹⁵ Mines ParisTech, F-77305 Cedex Fontainebleau, France.
¹⁶ Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal.
¹⁷ ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
¹⁸ Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, Brazil.
¹⁹ Jagiellonian University Medical College, Department of Haematology, Kraków, Poland.
²⁰ National Research Centre for the Working Environment, Copenhagen, Denmark.
²¹ UO Hematology, Department of Internal and Experimental Medicine, University of Pisa, Pisa, Italy.
²² Haematology Department, University Hospital of Salamanca & IBSAL, Salamanca, Spain.
²³ Department of Hematology, Rigshospitalet, Copenhagen, Denmark.
²⁴ Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
²⁵ National Center of Tumor Diseases, Heidelberg, Germany.

PMID: 27437873
PMCID: PMC5312293
DOI: 10.18632/oncotarget.10665

Meta-Analysis

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 et al. Oncotarget. 2016.

. 2016 Sep 13;7(37):59029-59048.

doi: 10.18632/oncotarget.10665.

Authors

Affiliations

¹ Genomic Oncology Area, Pfizer-University of Granada-Junta de Andalucía Centre for Genomics and Oncological Research (GENYO), Granada, Spain.
² Hematology Department, Virgen de las Nieves University Hospital, Granada, Spain.
³ Department of Biology, University of Pisa, Pisa, Italy.
⁴ Division of Biostatistics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
⁵ Myeloma Institute, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
⁶ Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany.
⁷ Department of Hematology, Hospital Universitario Doce de Octubre, Madrid, Spain.
⁸ Hematology and Medical Oncology Department, University Hospital Morales Meseguer, IMIB, Murcia, Spain.
⁹ Medical University of Lodz, Lodz, Poland.
¹⁰ INSERM UMR 1052/CNRS 5286, Universite Claude Bernard Lyon I, Lyon, France.
¹¹ Hematoloy Clinik, Holy Cross Cancer Center, Kielce, Poland.
¹² Institute Curie, Paris, France.
¹³ PSL Research University, Paris, France.
¹⁴ INSERM, U900, Paris, France.
¹⁵ Mines ParisTech, F-77305 Cedex Fontainebleau, France.
¹⁶ Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal.
¹⁷ ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
¹⁸ Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, Brazil.
¹⁹ Jagiellonian University Medical College, Department of Haematology, Kraków, Poland.
²⁰ National Research Centre for the Working Environment, Copenhagen, Denmark.
²¹ UO Hematology, Department of Internal and Experimental Medicine, University of Pisa, Pisa, Italy.
²² Haematology Department, University Hospital of Salamanca & IBSAL, Salamanca, Spain.
²³ Department of Hematology, Rigshospitalet, Copenhagen, Denmark.
²⁴ Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
²⁵ National Center of Tumor Diseases, Heidelberg, Germany.

PMID: 27437873
PMCID: PMC5312293
DOI: 10.18632/oncotarget.10665

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.

Keywords: diabetes; genetic variants; multiple myeloma; survival.

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Conflict of interest statement

CONFLICTS OF INTEREST

All authors have nothing to disclose.

Figures

**Figure 1. Kaplan-Meier plots for the *HNF1B*_rs7501939 SNP in the IMMENSE (A) and Heidelberg (B) populations**

See this image and copyright information in PMC

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

Affiliations

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

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Abstract

Conflict of interest statement

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