Sequence variant on 8q24 confers susceptibility to urinary bladder cancer

Lambertus A. Kiemeney; Steinunn Thorlacius; Patrick Sulem; Frank Geller; Katja K.H. Aben; Simon N. Stacey; Julius Gudmundsson; Margret Jakobsdottir; Jon T. Bergthorsson; Asgeir Sigurdsson; Thorarinn Blondal; J. Alfred Witjes; Sita H. Vermeulen; Christina A. Hulsbergen-Van De Kaa; Dorine W. Swinkels; Martine Ploeg; Erik B. Cornel; Henk Vergunst; Thorgeir E. Thorgeirsson; Daniel Gudbjartsson; Sigurjon A. Gudjonsson; Gudmar Thorleifsson; Kari T. Kristinsson; Magali Mouy; Steinunn Snorradottir; Donatella Placidi; Marcello Campagna; Cecilia Arici; Kvetoslava Koppova; Eugene Gurzau; Peter Rudnai; Eliane Kellen; Silvia Polidoro; Simonetta Guarrera; Carlotta Sacerdote; Manuel Sanchez; Berta Saez; Gabriel Valdivia; Charlotta Ryk; Petra De Verdier; Annika Lindblom; Klaus Golka; D. Timothy Bishop; Margaret A. Knowles; Sigfus Nikulasson; Vigdis Petursdottir; Eirikur Jonsson; Gudmundur Geirsson; Baldvin Kristjansson; Jose I. Mayordomo; Gunnar Steineck; Stefano Porru; Frank Buntinx; Maurice P. Zeegers; Tony Fletcher; Rajiv Kumar; Giuseppe Matullo; Paolo Vineis; Anne E. Kiltie; Jeffrey R. Gulcher; Unnur Thorsteinsdottir; Augustine Kong; Thorunn Rafnar; Kari Stefansson

doi:10.1038/ng.229

Sequence variant on 8q24 confers susceptibility to urinary bladder cancer

Lambertus A. Kiemeney, Steinunn Thorlacius, Patrick Sulem, Frank Geller, Katja K.H. Aben, Simon N. Stacey, Julius Gudmundsson, Margret Jakobsdottir, Jon T. Bergthorsson, Asgeir Sigurdsson, Thorarinn Blondal, J. Alfred Witjes, Sita H. Vermeulen, Christina A. Hulsbergen-Van De Kaa, Dorine W. Swinkels, Martine Ploeg, Erik B. Cornel, Henk Vergunst, Thorgeir E. Thorgeirsson, Daniel GudbjartssonSigurjon A. Gudjonsson, Gudmar Thorleifsson, Kari T. Kristinsson, Magali Mouy, Steinunn Snorradottir, Donatella Placidi, Marcello Campagna, Cecilia Arici, Kvetoslava Koppova, Eugene Gurzau, Peter Rudnai, Eliane Kellen, Silvia Polidoro, Simonetta Guarrera, Carlotta Sacerdote, Manuel Sanchez, Berta Saez, Gabriel Valdivia, Charlotta Ryk, Petra De Verdier, Annika Lindblom, Klaus Golka, D. Timothy Bishop, Margaret A. Knowles, Sigfus Nikulasson, Vigdis Petursdottir, Eirikur Jonsson, Gudmundur Geirsson, Baldvin Kristjansson, Jose I. Mayordomo, Gunnar Steineck, Stefano Porru, Frank Buntinx, Maurice P. Zeegers, Tony Fletcher, Rajiv Kumar, Giuseppe Matullo, Paolo Vineis, Anne E. Kiltie, Jeffrey R. Gulcher, Unnur Thorsteinsdottir, Augustine Kong, Thorunn Rafnar, Kari Stefansson

The Rowett Institute of Nutrition and Health

Research output: Contribution to journal › Article › peer-review

355 Citations (Scopus)

Abstract

We conducted a genome-wide SNP association study on 1,803 urinary bladder cancer (UBC) cases and 34,336 controls from Iceland and The Netherlands and follow up studies in seven additional case-control groups (2,165 cases and 3,800 controls). The strongest association was observed with allele T of rs9642880 on chromosome 8q24, 30 kb upstream of MYC (allele-specific odds ratio (OR) = 1.22; P = 9.34 × 10^-12). Approximately 20% of individuals of European ancestry are homozygous for rs9642880[T], and their estimated risk of developing UBC is 1.49 times that of noncarriers. No association was observed between UBC and the four 8q24 variants previously associated with prostate, colorectal and breast cancers, nor did rs9642880 associate with any of these three cancers. A weaker signal, but nonetheless of genome-wide significance, was captured by rs710521[A] located near TP63 on chromosome 3q28 (allele-specific OR = 1.19; P = 1. 15 × 10^-7).

Original language	English
Pages (from-to)	1307-1312
Number of pages	6
Journal	Nature Genetics
Volume	40
Issue number	11
DOIs	https://doi.org/10.1038/ng.229
Publication status	Published - Nov 2008

Bibliographical note

Funding Information:
We thank the individuals that participated in the study and whose contribution made this work possible. We also thank the nurses at Noatun (deCODE’s participant recruitment center) and the personnel at the deCODE core facilities. We acknowledge the Icelandic Cancer Registry for assistance in the ascertainment of the Icelandic UBC cases. Collection of samples and data in Iceland and The Netherlands was funded in part by the European Commission (POLYGENE: LSHC-CT-2005-018827 and GENADDICT: LSHM-CT-2004-005166), the National Institute of Health (R01-DA017932) and a research investment grant of the Radboud University Nijmegen Medical Centre. The Leeds Bladder Cancer Study was funded by Cancer Research UK and Yorkshire Cancer Research. 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, the Italian Association for Cancer Research, Italy and the Piedmont Region Progetti di Ricerca Sanitaria Finalizzata.

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Kiemeney, L. A., Thorlacius, S., Sulem, P., Geller, F., Aben, K. K. H., Stacey, S. N., Gudmundsson, J., Jakobsdottir, M., Bergthorsson, J. T., Sigurdsson, A., Blondal, T., Witjes, J. A., Vermeulen, S. H., Hulsbergen-Van De Kaa, C. A., Swinkels, D. W., Ploeg, M., Cornel, E. B., Vergunst, H., Thorgeirsson, T. E., ... Stefansson, K. (2008). Sequence variant on 8q24 confers susceptibility to urinary bladder cancer. Nature Genetics, 40(11), 1307-1312. https://doi.org/10.1038/ng.229

Kiemeney, LA, Thorlacius, S, Sulem, P, Geller, F, Aben, KKH, Stacey, SN, Gudmundsson, J, Jakobsdottir, M, Bergthorsson, JT, Sigurdsson, A, Blondal, T, Witjes, JA, Vermeulen, SH, Hulsbergen-Van De Kaa, CA, Swinkels, DW, Ploeg, M, Cornel, EB, Vergunst, H, Thorgeirsson, TE, Gudbjartsson, D, Gudjonsson, SA, Thorleifsson, G, Kristinsson, KT, Mouy, M, Snorradottir, S, Placidi, D, Campagna, M, Arici, C, Koppova, K, Gurzau, E, Rudnai, P, Kellen, E, Polidoro, S, Guarrera, S, Sacerdote, C, Sanchez, M, Saez, B, Valdivia, G, Ryk, C, De Verdier, P, Lindblom, A, Golka, K, Bishop, DT, Knowles, MA, Nikulasson, S, Petursdottir, V, Jonsson, E, Geirsson, G, Kristjansson, B, Mayordomo, JI, Steineck, G, Porru, S, Buntinx, F, Zeegers, MP, Fletcher, T, Kumar, R, Matullo, G, Vineis, P, Kiltie, AE, Gulcher, JR, Thorsteinsdottir, U, Kong, A, Rafnar, T & Stefansson, K 2008, 'Sequence variant on 8q24 confers susceptibility to urinary bladder cancer', Nature Genetics, vol. 40, no. 11, pp. 1307-1312. https://doi.org/10.1038/ng.229

@article{ffc41cf22f6b4e4292ef13c9c0de6687,

title = "Sequence variant on 8q24 confers susceptibility to urinary bladder cancer",

abstract = "We conducted a genome-wide SNP association study on 1,803 urinary bladder cancer (UBC) cases and 34,336 controls from Iceland and The Netherlands and follow up studies in seven additional case-control groups (2,165 cases and 3,800 controls). The strongest association was observed with allele T of rs9642880 on chromosome 8q24, 30 kb upstream of MYC (allele-specific odds ratio (OR) = 1.22; P = 9.34 × 10-12). Approximately 20% of individuals of European ancestry are homozygous for rs9642880[T], and their estimated risk of developing UBC is 1.49 times that of noncarriers. No association was observed between UBC and the four 8q24 variants previously associated with prostate, colorectal and breast cancers, nor did rs9642880 associate with any of these three cancers. A weaker signal, but nonetheless of genome-wide significance, was captured by rs710521[A] located near TP63 on chromosome 3q28 (allele-specific OR = 1.19; P = 1. 15 × 10-7).",

author = "Kiemeney, {Lambertus A.} and Steinunn Thorlacius and Patrick Sulem and Frank Geller and Aben, {Katja K.H.} and Stacey, {Simon N.} and Julius Gudmundsson and Margret Jakobsdottir and Bergthorsson, {Jon T.} and Asgeir Sigurdsson and Thorarinn Blondal and Witjes, {J. Alfred} and Vermeulen, {Sita H.} and {Hulsbergen-Van De Kaa}, {Christina A.} and Swinkels, {Dorine W.} and Martine Ploeg and Cornel, {Erik B.} and Henk Vergunst and Thorgeirsson, {Thorgeir E.} and Daniel Gudbjartsson and Gudjonsson, {Sigurjon A.} and Gudmar Thorleifsson and Kristinsson, {Kari T.} and Magali Mouy and Steinunn Snorradottir and Donatella Placidi and Marcello Campagna and Cecilia Arici and Kvetoslava Koppova and Eugene Gurzau and Peter Rudnai and Eliane Kellen and Silvia Polidoro and Simonetta Guarrera and Carlotta Sacerdote and Manuel Sanchez and Berta Saez and Gabriel Valdivia and Charlotta Ryk and {De Verdier}, Petra and Annika Lindblom and Klaus Golka and Bishop, {D. Timothy} and Knowles, {Margaret A.} and Sigfus Nikulasson and Vigdis Petursdottir and Eirikur Jonsson and Gudmundur Geirsson and Baldvin Kristjansson and Mayordomo, {Jose I.} and Gunnar Steineck and Stefano Porru and Frank Buntinx and Zeegers, {Maurice P.} and Tony Fletcher and Rajiv Kumar and Giuseppe Matullo and Paolo Vineis and Kiltie, {Anne E.} and Gulcher, {Jeffrey R.} and Unnur Thorsteinsdottir and Augustine Kong and Thorunn Rafnar and Kari Stefansson",

note = "Funding Information: We thank the individuals that participated in the study and whose contribution made this work possible. We also thank the nurses at Noatun (deCODE{\textquoteright}s participant recruitment center) and the personnel at the deCODE core facilities. We acknowledge the Icelandic Cancer Registry for assistance in the ascertainment of the Icelandic UBC cases. Collection of samples and data in Iceland and The Netherlands was funded in part by the European Commission (POLYGENE: LSHC-CT-2005-018827 and GENADDICT: LSHM-CT-2004-005166), the National Institute of Health (R01-DA017932) and a research investment grant of the Radboud University Nijmegen Medical Centre. The Leeds Bladder Cancer Study was funded by Cancer Research UK and Yorkshire Cancer Research. 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: {\textquoteleft}{\textquoteleft}Food Quality and Safety{\textquoteright}{\textquoteright} (Contract No 513943); by a grant of the compagnia di San Paolo, the Italian Association for Cancer Research, Italy and the Piedmont Region Progetti di Ricerca Sanitaria Finalizzata.",

year = "2008",

month = nov,

doi = "10.1038/ng.229",

language = "English",

volume = "40",

pages = "1307--1312",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "11",

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TY - JOUR

T1 - Sequence variant on 8q24 confers susceptibility to urinary bladder cancer

AU - Kiemeney, Lambertus A.

AU - Thorlacius, Steinunn

AU - Sulem, Patrick

AU - Geller, Frank

AU - Aben, Katja K.H.

AU - Stacey, Simon N.

AU - Gudmundsson, Julius

AU - Jakobsdottir, Margret

AU - Bergthorsson, Jon T.

AU - Sigurdsson, Asgeir

AU - Blondal, Thorarinn

AU - Witjes, J. Alfred

AU - Vermeulen, Sita H.

AU - Hulsbergen-Van De Kaa, Christina A.

AU - Swinkels, Dorine W.

AU - Ploeg, Martine

AU - Cornel, Erik B.

AU - Vergunst, Henk

AU - Thorgeirsson, Thorgeir E.

AU - Gudbjartsson, Daniel

AU - Gudjonsson, Sigurjon A.

AU - Thorleifsson, Gudmar

AU - Kristinsson, Kari T.

AU - Mouy, Magali

AU - Snorradottir, Steinunn

AU - Placidi, Donatella

AU - Campagna, Marcello

AU - Arici, Cecilia

AU - Koppova, Kvetoslava

AU - Gurzau, Eugene

AU - Rudnai, Peter

AU - Kellen, Eliane

AU - Polidoro, Silvia

AU - Guarrera, Simonetta

AU - Sacerdote, Carlotta

AU - Sanchez, Manuel

AU - Saez, Berta

AU - Valdivia, Gabriel

AU - Ryk, Charlotta

AU - De Verdier, Petra

AU - Lindblom, Annika

AU - Golka, Klaus

AU - Bishop, D. Timothy

AU - Knowles, Margaret A.

AU - Nikulasson, Sigfus

AU - Petursdottir, Vigdis

AU - Jonsson, Eirikur

AU - Geirsson, Gudmundur

AU - Kristjansson, Baldvin

AU - Mayordomo, Jose I.

AU - Steineck, Gunnar

AU - Porru, Stefano

AU - Buntinx, Frank

AU - Zeegers, Maurice P.

AU - Fletcher, Tony

AU - Kumar, Rajiv

AU - Matullo, Giuseppe

AU - Vineis, Paolo

AU - Kiltie, Anne E.

AU - Gulcher, Jeffrey R.

AU - Thorsteinsdottir, Unnur

AU - Kong, Augustine

AU - Rafnar, Thorunn

AU - Stefansson, Kari

N1 - Funding Information: We thank the individuals that participated in the study and whose contribution made this work possible. We also thank the nurses at Noatun (deCODE’s participant recruitment center) and the personnel at the deCODE core facilities. We acknowledge the Icelandic Cancer Registry for assistance in the ascertainment of the Icelandic UBC cases. Collection of samples and data in Iceland and The Netherlands was funded in part by the European Commission (POLYGENE: LSHC-CT-2005-018827 and GENADDICT: LSHM-CT-2004-005166), the National Institute of Health (R01-DA017932) and a research investment grant of the Radboud University Nijmegen Medical Centre. The Leeds Bladder Cancer Study was funded by Cancer Research UK and Yorkshire Cancer Research. 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, the Italian Association for Cancer Research, Italy and the Piedmont Region Progetti di Ricerca Sanitaria Finalizzata.

PY - 2008/11

Y1 - 2008/11

N2 - We conducted a genome-wide SNP association study on 1,803 urinary bladder cancer (UBC) cases and 34,336 controls from Iceland and The Netherlands and follow up studies in seven additional case-control groups (2,165 cases and 3,800 controls). The strongest association was observed with allele T of rs9642880 on chromosome 8q24, 30 kb upstream of MYC (allele-specific odds ratio (OR) = 1.22; P = 9.34 × 10-12). Approximately 20% of individuals of European ancestry are homozygous for rs9642880[T], and their estimated risk of developing UBC is 1.49 times that of noncarriers. No association was observed between UBC and the four 8q24 variants previously associated with prostate, colorectal and breast cancers, nor did rs9642880 associate with any of these three cancers. A weaker signal, but nonetheless of genome-wide significance, was captured by rs710521[A] located near TP63 on chromosome 3q28 (allele-specific OR = 1.19; P = 1. 15 × 10-7).

AB - We conducted a genome-wide SNP association study on 1,803 urinary bladder cancer (UBC) cases and 34,336 controls from Iceland and The Netherlands and follow up studies in seven additional case-control groups (2,165 cases and 3,800 controls). The strongest association was observed with allele T of rs9642880 on chromosome 8q24, 30 kb upstream of MYC (allele-specific odds ratio (OR) = 1.22; P = 9.34 × 10-12). Approximately 20% of individuals of European ancestry are homozygous for rs9642880[T], and their estimated risk of developing UBC is 1.49 times that of noncarriers. No association was observed between UBC and the four 8q24 variants previously associated with prostate, colorectal and breast cancers, nor did rs9642880 associate with any of these three cancers. A weaker signal, but nonetheless of genome-wide significance, was captured by rs710521[A] located near TP63 on chromosome 3q28 (allele-specific OR = 1.19; P = 1. 15 × 10-7).

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U2 - 10.1038/ng.229

DO - 10.1038/ng.229

M3 - Article

C2 - 18794855

AN - SCOPUS:55049112064

SN - 1061-4036

VL - 40

SP - 1307

EP - 1312

JO - Nature Genetics

JF - Nature Genetics

IS - 11

ER -

Sequence variant on 8q24 confers susceptibility to urinary bladder cancer

Abstract

Bibliographical note

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