title: A common variant within the HNF1B gene is associated with overall survival of multiple myeloma patients: results from the IMMEnSE consortium and meta-analysis.
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.
authors.affiliation: Genomic Oncology Area, Pfizer-University of Granada-Junta de Andalucía Centre for Genomics and Oncological Research (GENYO), Granada, Spain.|Hematology Department, Virgen de las Nieves University Hospital, Granada, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Ríos-Tamayo
authors.affiliation: Genomic Oncology Area, Pfizer-University of Granada-Junta de Andalucía Centre for Genomics and Oncological Research (GENYO), Granada, Spain.|Hematology Department, Virgen de las Nieves University Hospital, Granada, Spain.
authors.forename: Carmen Belén
authors.initials: CB
authors.lastname: Lupiañez
authors.affiliation: Department of Biology, University of Pisa, Pisa, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Campa
authors.affiliation: Division of Biostatistics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hielscher
authors.affiliation: Myeloma Institute, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.|Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany.
authors.forename: Niels
authors.initials: N
authors.lastname: Weinhold
authors.affiliation: Department of Hematology, Hospital Universitario Doce de Octubre, Madrid, Spain.
authors.forename: Joaquin
authors.initials: J
authors.lastname: Martínez-López
authors.affiliation: Hematology and Medical Oncology Department, University Hospital Morales Meseguer, IMIB, Murcia, Spain.
authors.forename: Andrés
authors.initials: A
authors.lastname: Jerez
authors.affiliation: Department of Biology, University of Pisa, Pisa, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Landi
authors.affiliation: Medical University of Lodz, Lodz, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Jamroziak
authors.affiliation: INSERM UMR 1052/CNRS 5286, Universite Claude Bernard Lyon I, Lyon, France.
authors.forename: Charles
authors.initials: C
authors.lastname: Dumontet
authors.affiliation: Hematoloy Clinik, Holy Cross Cancer Center, Kielce, Poland.
authors.forename: Marzena
authors.initials: M
authors.lastname: Wątek
authors.affiliation: Institute Curie, Paris, France.|PSL Research University, Paris, France.|INSERM, U900, Paris, France.|Mines ParisTech, F-77305 Cedex Fontainebleau, France.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Lesueur
authors.affiliation: Life 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.|Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, Brazil.
authors.forename: Rui Manuel
authors.initials: RM
authors.lastname: Reis
authors.affiliation: Life 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.
authors.forename: Herlander
authors.initials: H
authors.lastname: Marques
authors.affiliation: Jagiellonian University Medical College, Department of Haematology, Kraków, Poland.
authors.forename: Artur
authors.initials: A
authors.lastname: Jurczyszyn
authors.affiliation: National Research Centre for the Working Environment, Copenhagen, Denmark.
authors.forename: Ulla
authors.initials: U
authors.lastname: Vogel
authors.affiliation: UO Hematology, Department of Internal and Experimental Medicine, University of Pisa, Pisa, Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Buda
authors.affiliation: Haematology Department, University Hospital of Salamanca & IBSAL, Salamanca, Spain.
authors.forename: Ramón
authors.initials: R
authors.lastname: García-Sanz
authors.affiliation: UO Hematology, Department of Internal and Experimental Medicine, University of Pisa, Pisa, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Orciuolo
authors.affiliation: UO Hematology, Department of Internal and Experimental Medicine, University of Pisa, Pisa, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Petrini
authors.affiliation: Department of Hematology, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Annette J
authors.initials: AJ
authors.lastname: Vangsted
authors.affiliation: Department of Biology, University of Pisa, Pisa, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Gemignani
authors.affiliation: Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Asta
authors.initials: A
authors.lastname: Försti
authors.affiliation: Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany.|National Center of Tumor Diseases, Heidelberg, Germany.
authors.forename: Hartmut
authors.initials: H
authors.lastname: Goldschmidt
authors.affiliation: Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Kari
authors.initials: K
authors.lastname: Hemminki
authors.affiliation: INSERM UMR 1052/CNRS 5286, Universite Claude Bernard Lyon I, Lyon, France.
authors.forename: Federico
authors.initials: F
authors.lastname: Canzian
authors.affiliation: Genomic Oncology Area, Pfizer-University of Granada-Junta de Andalucía Centre for Genomics and Oncological Research (GENYO), Granada, Spain.|Hematology Department, Virgen de las Nieves University Hospital, Granada, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Jurado
authors.affiliation: Genomic Oncology Area, Pfizer-University of Granada-Junta de Andalucía Centre for Genomics and Oncological Research (GENYO), Granada, Spain.|Hematology Department, Virgen de las Nieves University Hospital, Granada, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Sainz
mesh_terms: D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D051539:Hepatocyte Nuclear Factor 1-beta / Q000235:genetics*; D006801:Humans; D008297:Male; D009101:Multiple Myeloma / Q000235:genetics* / Q000401:mortality; D020641:Polymorphism, Single Nucleotide; D012737:Sex Factors; D016019:Survival Analysis; D000075703:Zinc Transporter 8 / Q000235:genetics*
chemical_list: C496495:HNF1B protein, human; C492522:SLC30A8 protein, human; D000075703:Zinc Transporter 8; D051539:Hepatocyte Nuclear Factor 1-beta
keywords: diabetes; genetic variants; multiple myeloma; survival