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

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Hum. Mol. Genet.-2011-Rafnar-h ...
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Authors
Rafnar, Thorunn
Vermeulen, Sita H
Sulem, Patrick
Thorleifsson, Gudmar
Aben, Katja K
Witjes, J Alfred
Grotenhuis, Anne J
Verhaegh, Gerald W
Hulsbergen-van de Kaa, Christina A
Besenbacher, Soren
Gudbjartsson, Daniel
Stacey, Simon N
Gudmundsson, Julius
Johannsdottir, Hrefna
Bjarnason, Hjordis
Zanon, Carlo
Helgadottir, Hafdis
Jonasson, Jon Gunnlaugur
Tryggvadottir, Laufey
Jonsson, Eirikur
Geirsson, Gudmundur
Nikulasson, Sigfus
Petursdottir, Vigdis
Bishop, D Timothy
Chung-Sak, Sei
Choudhury, Ananya
Elliott, Faye
Barrett, Jennifer H
Knowles, Margaret A
de Verdier, Petra J
Ryk, Charlotta
Lindblom, Annika
Rudnai, Peter
Gurzau, Eugene
Koppova, Kvetoslava
Vineis, Paolo
Polidoro, Silvia
Guarrera, Simonetta
Sacerdote, Carlotta
Panadero, Angeles
Sanz-Velez, José I
Sanchez, Manuel
Valdivia, Gabriel
Garcia-Prats, Maria D
Hengstler, Jan G
Selinski, Silvia
Gerullis, Holger
Ovsiannikov, Daniel
Khezri, Abdolaziz
Aminsharifi, Alireza
Malekzadeh, Mahyar
van den Berg, Leonard H
Ophoff, Roel A
Veldink, Jan H
Zeegers, Maurice P
Kellen, Eliane
Fostinelli, Jacopo
Andreoli, Daniele
Arici, Cecilia
Porru, Stefano
Buntinx, Frank
Ghaderi, Abbas
Golka, Klaus
Mayordomo, José I
Matullo, Giuseppe
Kumar, Rajiv
Steineck, Gunnar
Kiltie, Anne E
Kong, Augustine
Thorsteinsdottir, Unnur
Stefansson, Kari
Kiemeney, Lambertus A
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Issue Date
2011-11-01

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Citation
Hum. Mol. Genet. 2011, 20(21):4268-81
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.
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http://dx.doi.org/10.1093/hmg/ddr303
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openAccess
ae974a485f413a2113503eed53cd6c53
10.1093/hmg/ddr303
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