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

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

doi:10.1093/hmg/ddr303

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

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

Risultato della ricerca: Contributo su rivista › Articolo in rivista › peer review

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 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 3 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.

Lingua originale	Inglese
Numero di articolo	ddr303
pagine (da-a)	4268-4281
Numero di pagine	14
Rivista	Human Molecular Genetics
Volume	20
Numero di pubblicazione	21
DOI	https://doi.org/10.1093/hmg/ddr303
Stato di pubblicazione	Pubblicato - nov 2011
Pubblicato esternamente	Sì

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Rafnar, T., Vermeulen, S. H., Sulem, P., Thorleifsson, G., Aben, K. K., Witjes, J. A., Grotenhuis, A. J., Verhaegh, G. W., van de Kaa, C. A. H., Besenbacher, S., Gudbjartsson, D., Stacey, S. N., Gudmundsson, J., Johannsdottir, H., Bjarnason, H., Zanon, C., Helgadottir, H., Jonasson, J. G., Tryggvadottir, L., ... Kiemeney, L. A. (2011). European genome-wide association study identifies SLC14A1 as a new urinary bladder cancer susceptibility gene. Human Molecular Genetics, 20(21), 4268-4281. Articolo ddr303. https://doi.org/10.1093/hmg/ddr303

@article{ba7cea1782d04f069dd2e9ebae5b6ee1,

title = "European genome-wide association study identifies SLC14A1 as a new urinary bladder cancer susceptibility gene",

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 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 3 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.",

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

year = "2011",

month = nov,

doi = "10.1093/hmg/ddr303",

language = "English",

volume = "20",

pages = "4268--4281",

journal = "Human Molecular Genetics",

issn = "0964-6906",

publisher = "Oxford University Press",

number = "21",

}

Rafnar, T, Vermeulen, SH, Sulem, P, Thorleifsson, G, Aben, KK, Witjes, JA, Grotenhuis, AJ, Verhaegh, GW, van de Kaa, CAH, Besenbacher, S, Gudbjartsson, D, Stacey, SN, Gudmundsson, J, Johannsdottir, H, Bjarnason, H, Zanon, C, Helgadottir, H, Jonasson, JG, Tryggvadottir, L, Jonsson, E, Geirsson, G, Nikulasson, S, Petursdottir, V, Bishop, DT, Chung-Sak, S, Choudhury, A, Elliott, F, Barrett, JH, Knowles, MA, de Verdier, PJ, Ryk, C, Lindblom, A, Rudnai, P, Gurzau, E, Koppova, K, Vineis, P, Polidoro, S, Guarrera, S, Sacerdote, C, Panadero, A, Sanz-Velez, JI, Sanchez, M, Valdivia, G, Garcia-Prats, MD, Hengstler, JG, Selinski, S, Gerullis, H, Ovsiannikov, D, Khezri, A, Aminsharifi, A, Malekzadeh, M, van den Berg, LH, Ophoff, RA, Veldink, JH, Zeegers, MP, Kellen, E, Fostinelli, J, Andreoli, D, Arici, C, Porru, S, Buntinx, F, Ghaderi, A, Golka, K, Mayordomo, JI, Matullo, G, Kumar, R, Steineck, G, Kiltie, AE, Kong, A, Thorsteinsdottir, U, Stefansson, K & Kiemeney, LA 2011, 'European genome-wide association study identifies SLC14A1 as a new urinary bladder cancer susceptibility gene', Human Molecular Genetics, vol. 20, n. 21, ddr303, pagg. 4268-4281. https://doi.org/10.1093/hmg/ddr303

TY - JOUR

T1 - European genome-wide association study identifies SLC14A1 as a new urinary bladder cancer susceptibility gene

AU - Rafnar, Thorunn

AU - Vermeulen, Sita H.

AU - Sulem, Patrick

AU - Thorleifsson, Gudmar

AU - Aben, Katja K.

AU - Witjes, J. A.

AU - Grotenhuis, Anne J.

AU - Verhaegh, Gerald W.

AU - van de Kaa, Christina A.Hulsbergen

AU - Besenbacher, Soren

AU - Gudbjartsson, Daniel

AU - Stacey, Simon N.

AU - Gudmundsson, Julius

AU - Johannsdottir, Hrefna

AU - Bjarnason, Hjordis

AU - Zanon, Carlo

AU - Helgadottir, Hafdis

AU - Jonasson, Jon Gunnlaugur

AU - Tryggvadottir, Laufey

AU - Jonsson, Eirikur

AU - Geirsson, Gudmundur

AU - Nikulasson, Sigfus

AU - Petursdottir, Vigdis

AU - Bishop, D. Timothy

AU - Chung-Sak, Sei

AU - Choudhury, Ananya

AU - Elliott, Faye

AU - Barrett, Jennifer H.

AU - Knowles, Margaret A.

AU - de Verdier, Petra J.

AU - Ryk, Charlotta

AU - Lindblom, Annika

AU - Rudnai, Peter

AU - Gurzau, Eugene

AU - Koppova, Kvetoslava

AU - Vineis, Paolo

AU - Polidoro, Silvia

AU - Guarrera, Simonetta

AU - Sacerdote, Carlotta

AU - Panadero, Angeles

AU - Sanz-Velez, José I.

AU - Sanchez, Manuel

AU - Valdivia, Gabriel

AU - Garcia-Prats, Maria D.

AU - Hengstler, Jan G.

AU - Selinski, Silvia

AU - Gerullis, Holger

AU - Ovsiannikov, Daniel

AU - Khezri, Abdolaziz

AU - Aminsharifi, Alireza

AU - Malekzadeh, Mahyar

AU - van den Berg, Leonard H.

AU - Ophoff, Roel A.

AU - Veldink, Jan H.

AU - Zeegers, Maurice P.

AU - Kellen, Eliane

AU - Fostinelli, Jacopo

AU - Andreoli, Daniele

AU - Arici, Cecilia

AU - Porru, Stefano

AU - Buntinx, Frank

AU - Ghaderi, Abbas

AU - Golka, Klaus

AU - Mayordomo, José I.

AU - Matullo, Giuseppe

AU - Kumar, Rajiv

AU - Steineck, Gunnar

AU - Kiltie, Anne E.

AU - Kong, Augustine

AU - Thorsteinsdottir, Unnur

AU - Stefansson, Kari

AU - Kiemeney, Lambertus A.

PY - 2011/11

Y1 - 2011/11

N2 - 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 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 3 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.

AB - 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 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 3 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.

UR - http://www.scopus.com/inward/record.url?scp=80053945781&partnerID=8YFLogxK

U2 - 10.1093/hmg/ddr303

DO - 10.1093/hmg/ddr303

M3 - Article

SN - 0964-6906

VL - 20

SP - 4268

EP - 4281

JO - Human Molecular Genetics

JF - Human Molecular Genetics

IS - 21

M1 - ddr303

ER -

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

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