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    European genome-wide association study identifies SLC14A1 as a new urinary bladder cancer susceptibility gene.

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    Authors
    Rafnar, T
    Vermeulen, S H
    Sulem, P
    Thorleifsson, G
    Aben, Katja K H
    Witjes, J A
    Grotenhuis, A J
    Verhaegh, G W
    Hulsbergen-van de Kaa, C A
    Besenbacher, S
    Gudbjartsson, D
    Stacey, S N
    Gudmundsson, J
    Johannsdottir, H
    Bjarnason, H
    Zanon, C
    Helgadottir, H
    Jonasson, J G
    Tryggvadottir, L
    Jonsson, E
    Geirsson, G
    Nikulasson, S
    Petursdottir, V
    Bishop, D T
    Chung-Sak, S
    Choudhury, Ananya
    Elliott, F
    Barrett, J H
    Knowles, M A
    de Verdier, P J
    Ryk, C
    Lindblom, A
    Rudnai, P
    Gurzau, E
    Koppova, K
    Vineis, P
    Polidoro, S
    Guarrera, S
    Sacerdote, C
    Panadero, A
    Sanz-Velez, J I
    Sanchez, M
    Valdivia, G
    Garcia-Prats, M D
    Hengstler, J G
    Selinski, S
    Gerullis, H
    Ovsiannikov, D
    Khezri, A
    Aminsharifi, Al
    Malekzadeh, M
    van den Berg, L H
    Ophoff, R A
    Veldink, J H
    Zeegers, M P
    Kellen, E
    Fostinelli, J
    Andreoli, D
    Arici, C
    Porru, S
    Buntinx, F
    Ghaderi, A
    Golka, K
    Mayordomo, J I
    Matullo, G
    Kumar, R
    Steineck, G
    Kiltie, A E
    Kong, A
    Thorsteinsdottir, U
    Stefansson, K
    Kiemeney, L A
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    Affiliation
    deCODE Genetics, Sturlugata 8, 101 Reykjavik, Iceland.
    Issue Date
    2011-11-01
    
    Metadata
    Show full item record
    Abstract
    Three genome-wide association studies in Europe and the USA have reported eight urinary bladder cancer (UBC) susceptibility loci. Using extended case and control series and 1000 Genomes imputations of 5 340 737 single-nucleotide polymorphisms (SNPs), we searched for additional loci in the European GWAS. The discovery sample set consisted of 1631 cases and 3822 controls from the Netherlands and 603 cases and 37 781 controls from Iceland. For follow-up, we used 3790 cases and 7507 controls from 13 sample sets of European and Iranian ancestry. Based on the discovery analysis, we followed up signals in the urea transporter (UT) gene SLC14A. The strongest signal at this locus was represented by a SNP in intron 3, rs17674580, that reached genome-wide significance in the overall analysis of the discovery and follow-up groups: odds ratio = 1.17, P = 7.6 × 10(-11). SLC14A1 codes for UTs that define the Kidd blood group and are crucial for the maintenance of a constant urea concentration gradient in the renal medulla and, through this, the kidney's ability to concentrate urine. It is speculated that rs17674580, or other sequence variants in LD with it, indirectly modifies UBC risk by affecting urine production. If confirmed, this would support the 'urogenous contact hypothesis' that urine production and voiding frequency modify the risk of UBC.
    Citation
    European genome-wide association study identifies SLC14A1 as a new urinary bladder cancer susceptibility gene. 2011, 20 (21):4268-81 Hum Mol Genet
    Journal
    Human Molecular Genetics
    URI
    http://hdl.handle.net/10541/226175
    DOI
    10.1093/hmg/ddr303
    PubMed ID
    21750109
    Type
    Article
    Language
    en
    ISSN
    1460-2083
    ae974a485f413a2113503eed53cd6c53
    10.1093/hmg/ddr303
    Scopus Count
    Collections
    All Christie Publications
    Clinical Oncology

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