A sequence variant at 4p16.3 confers susceptibility to urinary bladder cancer

Lambertus A. Kiemeney, Patrick Sulem, Soren Besenbacher, Sita H. Vermeulen, Asgeir Sigurdsson, Gudmar Thorleifsson, Daniel F. Gudbjartsson, Simon N. Stacey, Julius Gudmundsson, Carlo Zanon, Jelena Kostic, Gisli Masson, Hjordis Bjarnason, Stefan T. Palsson, Oskar B. Skarphedinsson, Sigurjon A. Gudjonsson, J. Alfred Witjes, Anne J. Grotenhuis, Gerald W. Verhaegh, D. Timothy BishopSei Chung Sak, Ananya Choudhury, Faye Elliott, Jennifer H. Barrett, Carolyn D. Hurst, Petra J. De Verdier, Charlotta Ryk, P. Rudnai, Eugene Gurzau, Kvetoslava Koppova, Paolo Vineis, Silvia Polidoro, Simonetta Guarrera, Carlotta Sacerdote, Marcello Campagna, Donatella Placidi, Cecilia Arici, Maurice P. Zeegers, Eliane Kellen, Berta Saez Gutierrez, José I. Sanz-Velez, Manuel Sanchez-Zalabardo, Gabriel Valdivia, Maria D. Garcia-Prats, Jan G. Hengstler, Meinolf Blaszkewicz, Holger Dietrich, Roel A. Ophoff, Leonard H. Van Den Berg, Kristin Alexiusdottir, Kristleifur Kristjansson, Gudmundur Geirsson, Sigfus Nikulasson, Vigdis Petursdottir, Augustine Kong, Thorgeir Thorgeirsson, N. Aydin Mungan, Annika Lindblom, Michael A. Van Es, Stefano Porru, Frank Buntinx, Klaus Golka, José I. Mayordomo, Rajiv Kumar, Giuseppe Matullo, Gunnar Steineck, Anne E. Kiltie, Katja K H Aben, Eirikur Jonsson, Unnur Thorsteinsdottir, Margaret A. Knowles, Thorunn Rafnar, Kari Stefansson

Research output: Contribution to journalArticle

124 Citations (Scopus)

Abstract

Previously, we reported germline DNA variants associated with risk of urinary bladder cancer (UBC) in Dutch and Icelandic subjects. Here we expanded the Icelandic sample set and tested the top 20 markers from the combined analysis in several European case-control sample sets, with a total of 4,739 cases and 45,549 controls. The T allele of rs798766 on 4p16.3 was found to associate with UBC (odds ratio = 1.24, P = 9.9 × 10 12). rs798766 is located in an intron of TACC3, 70 kb from FGFR3, which often harbors activating somatic mutations in low-grade, noninvasive UBC. Notably, rs798766[T] shows stronger association with low-grade and low-stage UBC than with more aggressive forms of the disease and is associated with higher risk of recurrence in low-grade stage Ta tumors. The frequency of rs798766[T] is higher in Ta tumors that carry an activating mutation in FGFR3 than in Ta tumors with wild-type FGFR3. Our results show a link between germline variants, somatic mutations of FGFR3 and risk of UBC.

Original languageEnglish
Pages (from-to)415-419
Number of pages5
JournalNature Genetics
Volume42
Issue number5
DOIs
Publication statusPublished - May 2010

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Urinary Bladder Neoplasms
Mutation
Neoplasms
Introns
Alleles
Odds Ratio
Recurrence
DNA

ASJC Scopus subject areas

  • Genetics

Cite this

Kiemeney, L. A., Sulem, P., Besenbacher, S., Vermeulen, S. H., Sigurdsson, A., Thorleifsson, G., ... Stefansson, K. (2010). A sequence variant at 4p16.3 confers susceptibility to urinary bladder cancer. Nature Genetics, 42(5), 415-419. https://doi.org/10.1038/ng.558

A sequence variant at 4p16.3 confers susceptibility to urinary bladder cancer. / Kiemeney, Lambertus A.; Sulem, Patrick; Besenbacher, Soren; Vermeulen, Sita H.; Sigurdsson, Asgeir; Thorleifsson, Gudmar; Gudbjartsson, Daniel F.; Stacey, Simon N.; Gudmundsson, Julius; Zanon, Carlo; Kostic, Jelena; Masson, Gisli; Bjarnason, Hjordis; Palsson, Stefan T.; Skarphedinsson, Oskar B.; Gudjonsson, Sigurjon A.; Witjes, J. Alfred; Grotenhuis, Anne J.; Verhaegh, Gerald W.; Bishop, D. Timothy; Sak, Sei Chung; Choudhury, Ananya; Elliott, Faye; Barrett, Jennifer H.; Hurst, Carolyn D.; De Verdier, Petra J.; Ryk, Charlotta; Rudnai, P.; Gurzau, Eugene; Koppova, Kvetoslava; Vineis, Paolo; Polidoro, Silvia; Guarrera, Simonetta; Sacerdote, Carlotta; Campagna, Marcello; Placidi, Donatella; Arici, Cecilia; Zeegers, Maurice P.; Kellen, Eliane; Gutierrez, Berta Saez; Sanz-Velez, José I.; Sanchez-Zalabardo, Manuel; Valdivia, Gabriel; Garcia-Prats, Maria D.; Hengstler, Jan G.; Blaszkewicz, Meinolf; Dietrich, Holger; Ophoff, Roel A.; Van Den Berg, Leonard H.; Alexiusdottir, Kristin; Kristjansson, Kristleifur; Geirsson, Gudmundur; Nikulasson, Sigfus; Petursdottir, Vigdis; Kong, Augustine; Thorgeirsson, Thorgeir; Mungan, N. Aydin; Lindblom, Annika; Van Es, Michael A.; Porru, Stefano; Buntinx, Frank; Golka, Klaus; Mayordomo, José I.; Kumar, Rajiv; Matullo, Giuseppe; Steineck, Gunnar; Kiltie, Anne E.; Aben, Katja K H; Jonsson, Eirikur; Thorsteinsdottir, Unnur; Knowles, Margaret A.; Rafnar, Thorunn; Stefansson, Kari.

In: Nature Genetics, Vol. 42, No. 5, 05.2010, p. 415-419.

Research output: Contribution to journalArticle

Kiemeney, LA, Sulem, P, Besenbacher, S, Vermeulen, SH, Sigurdsson, A, Thorleifsson, G, Gudbjartsson, DF, Stacey, SN, Gudmundsson, J, Zanon, C, Kostic, J, Masson, G, Bjarnason, H, Palsson, ST, Skarphedinsson, OB, Gudjonsson, SA, Witjes, JA, Grotenhuis, AJ, Verhaegh, GW, Bishop, DT, Sak, SC, Choudhury, A, Elliott, F, Barrett, JH, Hurst, CD, De Verdier, PJ, Ryk, C, Rudnai, P, Gurzau, E, Koppova, K, Vineis, P, Polidoro, S, Guarrera, S, Sacerdote, C, Campagna, M, Placidi, D, Arici, C, Zeegers, MP, Kellen, E, Gutierrez, BS, Sanz-Velez, JI, Sanchez-Zalabardo, M, Valdivia, G, Garcia-Prats, MD, Hengstler, JG, Blaszkewicz, M, Dietrich, H, Ophoff, RA, Van Den Berg, LH, Alexiusdottir, K, Kristjansson, K, Geirsson, G, Nikulasson, S, Petursdottir, V, Kong, A, Thorgeirsson, T, Mungan, NA, Lindblom, A, Van Es, MA, Porru, S, Buntinx, F, Golka, K, Mayordomo, JI, Kumar, R, Matullo, G, Steineck, G, Kiltie, AE, Aben, KKH, Jonsson, E, Thorsteinsdottir, U, Knowles, MA, Rafnar, T & Stefansson, K 2010, 'A sequence variant at 4p16.3 confers susceptibility to urinary bladder cancer', Nature Genetics, vol. 42, no. 5, pp. 415-419. https://doi.org/10.1038/ng.558
Kiemeney LA, Sulem P, Besenbacher S, Vermeulen SH, Sigurdsson A, Thorleifsson G et al. A sequence variant at 4p16.3 confers susceptibility to urinary bladder cancer. Nature Genetics. 2010 May;42(5):415-419. https://doi.org/10.1038/ng.558
Kiemeney, Lambertus A. ; Sulem, Patrick ; Besenbacher, Soren ; Vermeulen, Sita H. ; Sigurdsson, Asgeir ; Thorleifsson, Gudmar ; Gudbjartsson, Daniel F. ; Stacey, Simon N. ; Gudmundsson, Julius ; Zanon, Carlo ; Kostic, Jelena ; Masson, Gisli ; Bjarnason, Hjordis ; Palsson, Stefan T. ; Skarphedinsson, Oskar B. ; Gudjonsson, Sigurjon A. ; Witjes, J. Alfred ; Grotenhuis, Anne J. ; Verhaegh, Gerald W. ; Bishop, D. Timothy ; Sak, Sei Chung ; Choudhury, Ananya ; Elliott, Faye ; Barrett, Jennifer H. ; Hurst, Carolyn D. ; De Verdier, Petra J. ; Ryk, Charlotta ; Rudnai, P. ; Gurzau, Eugene ; Koppova, Kvetoslava ; Vineis, Paolo ; Polidoro, Silvia ; Guarrera, Simonetta ; Sacerdote, Carlotta ; Campagna, Marcello ; Placidi, Donatella ; Arici, Cecilia ; Zeegers, Maurice P. ; Kellen, Eliane ; Gutierrez, Berta Saez ; Sanz-Velez, José I. ; Sanchez-Zalabardo, Manuel ; Valdivia, Gabriel ; Garcia-Prats, Maria D. ; Hengstler, Jan G. ; Blaszkewicz, Meinolf ; Dietrich, Holger ; Ophoff, Roel A. ; Van Den Berg, Leonard H. ; Alexiusdottir, Kristin ; Kristjansson, Kristleifur ; Geirsson, Gudmundur ; Nikulasson, Sigfus ; Petursdottir, Vigdis ; Kong, Augustine ; Thorgeirsson, Thorgeir ; Mungan, N. Aydin ; Lindblom, Annika ; Van Es, Michael A. ; Porru, Stefano ; Buntinx, Frank ; Golka, Klaus ; Mayordomo, José I. ; Kumar, Rajiv ; Matullo, Giuseppe ; Steineck, Gunnar ; Kiltie, Anne E. ; Aben, Katja K H ; Jonsson, Eirikur ; Thorsteinsdottir, Unnur ; Knowles, Margaret A. ; Rafnar, Thorunn ; Stefansson, Kari. / A sequence variant at 4p16.3 confers susceptibility to urinary bladder cancer. In: Nature Genetics. 2010 ; Vol. 42, No. 5. pp. 415-419.
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AU - Kiemeney, Lambertus A.

AU - Sulem, Patrick

AU - Besenbacher, Soren

AU - Vermeulen, Sita H.

AU - Sigurdsson, Asgeir

AU - Thorleifsson, Gudmar

AU - Gudbjartsson, Daniel F.

AU - Stacey, Simon N.

AU - Gudmundsson, Julius

AU - Zanon, Carlo

AU - Kostic, Jelena

AU - Masson, Gisli

AU - Bjarnason, Hjordis

AU - Palsson, Stefan T.

AU - Skarphedinsson, Oskar B.

AU - Gudjonsson, Sigurjon A.

AU - Witjes, J. Alfred

AU - Grotenhuis, Anne J.

AU - Verhaegh, Gerald W.

AU - Bishop, D. Timothy

AU - Sak, Sei Chung

AU - Choudhury, Ananya

AU - Elliott, Faye

AU - Barrett, Jennifer H.

AU - Hurst, Carolyn D.

AU - De Verdier, Petra J.

AU - Ryk, Charlotta

AU - Rudnai, P.

AU - Gurzau, Eugene

AU - Koppova, Kvetoslava

AU - Vineis, Paolo

AU - Polidoro, Silvia

AU - Guarrera, Simonetta

AU - Sacerdote, Carlotta

AU - Campagna, Marcello

AU - Placidi, Donatella

AU - Arici, Cecilia

AU - Zeegers, Maurice P.

AU - Kellen, Eliane

AU - Gutierrez, Berta Saez

AU - Sanz-Velez, José I.

AU - Sanchez-Zalabardo, Manuel

AU - Valdivia, Gabriel

AU - Garcia-Prats, Maria D.

AU - Hengstler, Jan G.

AU - Blaszkewicz, Meinolf

AU - Dietrich, Holger

AU - Ophoff, Roel A.

AU - Van Den Berg, Leonard H.

AU - Alexiusdottir, Kristin

AU - Kristjansson, Kristleifur

AU - Geirsson, Gudmundur

AU - Nikulasson, Sigfus

AU - Petursdottir, Vigdis

AU - Kong, Augustine

AU - Thorgeirsson, Thorgeir

AU - Mungan, N. Aydin

AU - Lindblom, Annika

AU - Van Es, Michael A.

AU - Porru, Stefano

AU - Buntinx, Frank

AU - Golka, Klaus

AU - Mayordomo, José I.

AU - Kumar, Rajiv

AU - Matullo, Giuseppe

AU - Steineck, Gunnar

AU - Kiltie, Anne E.

AU - Aben, Katja K H

AU - Jonsson, Eirikur

AU - Thorsteinsdottir, Unnur

AU - Knowles, Margaret A.

AU - Rafnar, Thorunn

AU - Stefansson, Kari

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