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

2.50
Hdl Handle:
http://hdl.handle.net/10146/196490
Title:
European genome-wide association study identifies SLC14A1 as a new urinary bladder cancer susceptibility gene.
Authors:
Rafnar, Thorunn; Vermeulen, Sita H.; Sulem, Patrick; Thorleifsson, Gudmar; Aben, Katja K.H.; 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.
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:
Hum. Mol. Genet. 2011, 20 (21):4268-4281
Journal:
Human Molecular Genetics
Issue Date:
1-Nov-2011
URI:
http://hdl.handle.net/10146/196490
DOI:
10.1093/hmg/ddr303
PubMed ID:
21750109
Additional Links:
http://hmg.oxfordjournals.org/content/20/21/4268.long
Type:
Article
Language:
en
ISSN:
1460-2083
Sponsors:
This work was supported by the following funding agencies.Torino Bladder Cancer Case Control Study was supported by a grant to ECNIS (Environmental Cancer Risk, Nutrition and Individual Susceptibility), a network of excellence operating within the European Union 6th Framework Program, Priority 5: ‘Food Quality and Safety’ (Contract No. 513943); by a grant of the Compagnia di San Paolo—Human Genetics Foundation (HuGeF), the Italian Association for Cancer Research, Italy and the Piedmont Region Progetti di Ricerca Sanitaria Finalizzata.
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DC FieldValue Language
dc.contributor.authorRafnar, Thorunnen
dc.contributor.authorVermeulen, Sita H.en
dc.contributor.authorSulem, Patricken
dc.contributor.authorThorleifsson, Gudmaren
dc.contributor.authorAben, Katja K.H.en
dc.contributor.authorWitjes, J. Alfreden
dc.contributor.authorGrotenhuis, Anne J.en
dc.contributor.authorVerhaegh, Gerald W.en
dc.contributor.authorHulsbergen-van de Kaa, Christina A.en
dc.contributor.authorBesenbacher, Sorenen
dc.contributor.authorGudbjartsson, Danielen
dc.contributor.authorStacey, Simon N.en
dc.contributor.authorGudmundsson, Juliusen
dc.contributor.authorJohannsdottir, Hrefnaen
dc.contributor.authorBjarnason, Hjordisen
dc.contributor.authorZanon, Carloen
dc.contributor.authorHelgadottir, Hafdisen
dc.contributor.authorJonasson, Jon Gunnlauguren
dc.contributor.authorTryggvadottir, Laufeyen
dc.contributor.authorJonsson, Eirikuren
dc.contributor.authorGeirsson, Gudmunduren
dc.contributor.authorNikulasson, Sigfusen
dc.contributor.authorPetursdottir, Vigdisen
dc.contributor.authorBishop, D. Timothyen
dc.contributor.authorChung-Sak, Seien
dc.contributor.authorChoudhury, Ananyaen
dc.contributor.authorElliott, Fayeen
dc.contributor.authorBarrett, Jennifer H.en
dc.contributor.authorKnowles, Margaret A.en
dc.contributor.authorde Verdier, Petra J.en
dc.contributor.authorRyk, Charlottaen
dc.contributor.authorLindblom, Annikaen
dc.contributor.authorRudnai, Peteren
dc.contributor.authorGurzau, Eugeneen
dc.contributor.authorKoppova, Kvetoslavaen
dc.contributor.authorVineis, Paoloen
dc.contributor.authorPolidoro, Silviaen
dc.contributor.authorGuarrera, Simonettaen
dc.contributor.authorSacerdote, Carlottaen
dc.contributor.authorPanadero, Angelesen
dc.contributor.authorSanz-Velez, José I.en
dc.contributor.authorSanchez, Manuelen
dc.contributor.authorValdivia, Gabrielen
dc.contributor.authorGarcia-Prats, Maria D.en
dc.contributor.authorHengstler, Jan G.en
dc.contributor.authorSelinski, Silviaen
dc.contributor.authorGerullis, Holgeren
dc.contributor.authorOvsiannikov, Danielen
dc.contributor.authorKhezri, Abdolazizen
dc.contributor.authorAminsharifi, Alirezaen
dc.contributor.authorMalekzadeh, Mahyaren
dc.contributor.authorvan den Berg, Leonard H.en
dc.contributor.authorOphoff, Roel A.en
dc.contributor.authorVeldink, Jan H.en
dc.contributor.authorZeegers, Maurice P.en
dc.contributor.authorKellen, Elianeen
dc.contributor.authorFostinelli, Jacopoen
dc.contributor.authorAndreoli, Danieleen
dc.contributor.authorArici, Ceciliaen
dc.contributor.authorPorru, Stefanoen
dc.contributor.authorBuntinx, Franken
dc.contributor.authorGhaderi, Abbasen
dc.contributor.authorGolka, Klausen
dc.contributor.authorMayordomo, José I.en
dc.contributor.authorMatullo, Giuseppeen
dc.contributor.authorKumar, Rajiven
dc.contributor.authorSteineck, Gunnaren
dc.contributor.authorKiltie, Anne E.en
dc.contributor.authorKong, Augustineen
dc.contributor.authorThorsteinsdottir, Unnuren
dc.contributor.authorStefansson, Karien
dc.contributor.authorKiemeney, Lambertus A.en
dc.date.accessioned2011-12-08T12:36:05Z-
dc.date.available2011-12-08T12:36:05Z-
dc.date.issued2011-11-01-
dc.identifier.citationHum. Mol. Genet. 2011, 20 (21):4268-4281en
dc.identifier.issn1460-2083-
dc.identifier.pmid21750109-
dc.identifier.doi10.1093/hmg/ddr303-
dc.identifier.urihttp://hdl.handle.net/10146/196490-
dc.description.abstractThree 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.en
dc.description.sponsorshipThis work was supported by the following funding agencies.Torino Bladder Cancer Case Control Study was supported by a grant to ECNIS (Environmental Cancer Risk, Nutrition and Individual Susceptibility), a network of excellence operating within the European Union 6th Framework Program, Priority 5: ‘Food Quality and Safety’ (Contract No. 513943); by a grant of the Compagnia di San Paolo—Human Genetics Foundation (HuGeF), the Italian Association for Cancer Research, Italy and the Piedmont Region Progetti di Ricerca Sanitaria Finalizzata.en
dc.language.isoenen
dc.relation.urlhttp://hmg.oxfordjournals.org/content/20/21/4268.longen
dc.subjectUrinary bladder canceren
dc.subjectSusceptibilityen
dc.subjectHumanen
dc.subjectCancer risken
dc.subjectGenotypeen
dc.subject.meshAdulten
dc.subject.meshAgeden
dc.subject.meshAged, 80 and overen
dc.subject.meshChromosomes, Human, Pair 18en
dc.subject.meshDisease Progressionen
dc.subject.meshEuropean Continental Ancestry Groupen
dc.subject.meshFemaleen
dc.subject.meshGenetic Locien
dc.subject.meshGenetic Predisposition to Diseaseen
dc.subject.meshGenome-Wide Association Studyen
dc.subject.meshHumansen
dc.subject.meshMaleen
dc.subject.meshMembrane Transport Proteinsen
dc.subject.meshMiddle Ageden
dc.subject.meshPolymorphism, Single Nucleotideen
dc.subject.meshReproducibility of Resultsen
dc.subject.meshRisk Factorsen
dc.subject.meshUrinary Bladder Neoplasmsen
dc.titleEuropean genome-wide association study identifies SLC14A1 as a new urinary bladder cancer susceptibility gene.en
dc.typeArticleen
dc.identifier.journalHuman Molecular Geneticsen

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