European genome-wide association study identifies SLC14A1 as a new urinary bladder cancer susceptibility gene
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 G...
Published in: | Human Molecular Genetics |
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Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
Format: | Article in Journal/Newspaper |
Language: | English |
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2011
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Online Access: | https://research.manchester.ac.uk/en/publications/ea37f289-f255-4331-8850-fa9fb629ecfd https://doi.org/10.1093/hmg/ddr303 |
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ftumanchesterpub:oai:pure.atira.dk:publications/ea37f289-f255-4331-8850-fa9fb629ecfd |
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The University of Manchester: Research Explorer |
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English |
topic |
Adult Aged 80 and over Chromosomes Human Pair 18/genetics Disease Progression European Continental Ancestry Group/genetics Female Genetic Loci/genetics Genetic Predisposition to Disease Genome-Wide Association Study Humans Male Membrane Transport Proteins/genetics Middle Aged Polymorphism Single Nucleotide/genetics Reproducibility of Results Risk Factors Urinary Bladder Neoplasms/genetics Young Adult |
spellingShingle |
Adult Aged 80 and over Chromosomes Human Pair 18/genetics Disease Progression European Continental Ancestry Group/genetics Female Genetic Loci/genetics Genetic Predisposition to Disease Genome-Wide Association Study Humans Male Membrane Transport Proteins/genetics Middle Aged Polymorphism Single Nucleotide/genetics Reproducibility of Results Risk Factors Urinary Bladder Neoplasms/genetics Young Adult 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 European genome-wide association study identifies SLC14A1 as a new urinary bladder cancer susceptibility gene |
topic_facet |
Adult Aged 80 and over Chromosomes Human Pair 18/genetics Disease Progression European Continental Ancestry Group/genetics Female Genetic Loci/genetics Genetic Predisposition to Disease Genome-Wide Association Study Humans Male Membrane Transport Proteins/genetics Middle Aged Polymorphism Single Nucleotide/genetics Reproducibility of Results Risk Factors Urinary Bladder Neoplasms/genetics Young Adult |
description |
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. |
format |
Article in Journal/Newspaper |
author |
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 |
author_facet |
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 |
author_sort |
Rafnar, Thorunn |
title |
European genome-wide association study identifies SLC14A1 as a new urinary bladder cancer susceptibility gene |
title_short |
European genome-wide association study identifies SLC14A1 as a new urinary bladder cancer susceptibility gene |
title_full |
European genome-wide association study identifies SLC14A1 as a new urinary bladder cancer susceptibility gene |
title_fullStr |
European genome-wide association study identifies SLC14A1 as a new urinary bladder cancer susceptibility gene |
title_full_unstemmed |
European genome-wide association study identifies SLC14A1 as a new urinary bladder cancer susceptibility gene |
title_sort |
european genome-wide association study identifies slc14a1 as a new urinary bladder cancer susceptibility gene |
publishDate |
2011 |
url |
https://research.manchester.ac.uk/en/publications/ea37f289-f255-4331-8850-fa9fb629ecfd https://doi.org/10.1093/hmg/ddr303 |
genre |
Iceland |
genre_facet |
Iceland |
op_source |
Rafnar , T , Vermeulen , S H , Sulem , P , Thorleifsson , G , Aben , K K , 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 , A , 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 , A , 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 2011 , ' European genome-wide association study identifies SLC14A1 as a new urinary bladder cancer susceptibility gene ' , Human Molecular Genetics , vol. 20 , no. 21 , pp. 4268-81 . https://doi.org/10.1093/hmg/ddr303 |
op_rights |
info:eu-repo/semantics/restrictedAccess |
op_doi |
https://doi.org/10.1093/hmg/ddr303 |
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Human Molecular Genetics |
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ftumanchesterpub:oai:pure.atira.dk:publications/ea37f289-f255-4331-8850-fa9fb629ecfd 2023-11-12T04:19:27+01:00 European genome-wide association study identifies SLC14A1 as a new urinary bladder cancer susceptibility gene 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 2011-11-01 https://research.manchester.ac.uk/en/publications/ea37f289-f255-4331-8850-fa9fb629ecfd https://doi.org/10.1093/hmg/ddr303 eng eng info:eu-repo/semantics/restrictedAccess Rafnar , T , Vermeulen , S H , Sulem , P , Thorleifsson , G , Aben , K K , 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 , A , 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 , A , 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 2011 , ' European genome-wide association study identifies SLC14A1 as a new urinary bladder cancer susceptibility gene ' , Human Molecular Genetics , vol. 20 , no. 21 , pp. 4268-81 . https://doi.org/10.1093/hmg/ddr303 Adult Aged 80 and over Chromosomes Human Pair 18/genetics Disease Progression European Continental Ancestry Group/genetics Female Genetic Loci/genetics Genetic Predisposition to Disease Genome-Wide Association Study Humans Male Membrane Transport Proteins/genetics Middle Aged Polymorphism Single Nucleotide/genetics Reproducibility of Results Risk Factors Urinary Bladder Neoplasms/genetics Young Adult article 2011 ftumanchesterpub https://doi.org/10.1093/hmg/ddr303 2023-10-30T09:12:21Z 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. Article in Journal/Newspaper Iceland The University of Manchester: Research Explorer Human Molecular Genetics 20 21 4268 4281 |