A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci

Nathaniel Rothman, Montserrat Garcia-Closas, Nilanjan Chatterjee, Nuria Malats, Xifeng Wu, Jonine D. Figueroa, Francisco X. Real, David Van Den Berg, Giuseppe Matullo, Dalsu Baris, Michael Thun, Lambertus A. Kiemeney, Paolo Vineis, Immaculata De Vivo, Demetrius Albanes, Mark P. Purdue, Thorunn Rafnar, Michelle A.T. Hildebrandt, Anne E. Kiltie, Olivier CussenotKlaus Golka, Rajiv Kumar, Jack A. Taylor, Jose I. Mayordomo, Kevin B. Jacobs, Manolis Kogevinas, Amy Hutchinson, Zhaoming Wang, Yi Ping Fu, Ludmila Prokunina-Oolsson, Laurie BurdeT, Meredith Yeager, William Wheeler, Adonina Tardón, Consol Serra, Alfredo Carrato, Reina García-Cclosas, Josep Loreta, Alison Johnson, Molly Schwenn, Margaret R. Karagas, Alan Schned, Gerald Andriole, Robert Grubb, Amanda Black, Eric J. Jacobs, W. Ryan Diver, Susan M. Gapstur, Stephanie J. Weinstein, Jarmo Virtamo, Victoria K. Cortessis, Manuela Gago-Dominguez, Malcolm C. Pike, Mariana C. Stern, Jian Min Yuan, David J. Hunter, Monica McGgrath, Colin P. Dinney, Bogdan Czerniak, Meng Chen, Hushan Yang, Sita H. Vermeulen, Katja K. Aben, J. Alfred Witjes, Remco R. MaKinje, Patrick Sulem, Soren Besenbacher, Kari Stefansson, Elio Riboli, Paul Brennan, Salvatore Panico, Carmen Navarro, Naomi E. Allen, H. Bas Bueno-De-Mesquita, Dimitrios Trichopoulos, Neil Caporaso, Maria Teresa Landi, Federico Canzian, Borje Ljungberg, Anne Tjonneland, Francoise Clavel-Chapelon, David T. Bishop, Mark T.W. Teo, Margaret A. Knowles, Simonetta Guarrera, Silvia Polidoro, Fulvio Ricceri, Carlotta Sacerdote, Alessandra Allione, Geraldine Cancel-Tassin, Silvia Selinski, Jan G. Hengstler, Holger Dietrich, Tony Fletcher, Peter Rudnai, Eugen Gurzau, Kvetoslava Koppova, Sophia C.E. Bolick, Ashley Godfrey, Zongli Xu, José I. Sanz-Velez, María D.García Prats, Manuel Sanchez, Gabriel Valdivia, Stefano Porru, Simone Benhamou, Robert N. Hoover, Joseph F. Fraumeni, Debra T. Silverman, Stephen J. Chanock

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Abstract

We conducted a multi-stage, genome-wide aSociation study of blaDer cancer with a primary scan of 591,637 SNPs in 3,532 affected individuals (cases) and 5,120 controls of European descent from five studies foLowed by a replication strategy, which included 8,382 cases and 48,275 controls from 16 studies. In a combined analysis, we identified thrE new regions aSociated with blaDer cancer on chromosomes 22q13.1, 19q12 and 2q37.1: rs1014971, (P = 8-10-12) maps to a non-genic region of chromosome 22q13.1, rs8102137 (P = 2-10-11) on 19q12 maps to CNE1 and rs11892031 (P = 1-10-7) maps to the UGT1A cluster on 2q37.1. We confirmed four previously identified genome-wide aSociations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate aSociations for the GSTM1 deletion (P = 4-10-11) and a tag SNP for NAT2 acetylation status (P = 4-10-11), and found interactions with smoking in both regions. Our findings on coMon variants aSociated with blaDer cancer risk should provide new insights into the mechanisms of carcinogenesis.

Original languageEnglish
Pages (from-to)978-984
Number of pages7
JournalNature genetics
Volume42
Issue number11
DOIs
Publication statusPublished - Nov 1 2010

ASJC Scopus subject areas

  • Genetics

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    Rothman, N., Garcia-Closas, M., Chatterjee, N., Malats, N., Wu, X., Figueroa, J. D., Real, F. X., Van Den Berg, D., Matullo, G., Baris, D., Thun, M., Kiemeney, L. A., Vineis, P., De Vivo, I., Albanes, D., Purdue, M. P., Rafnar, T., Hildebrandt, M. A. T., Kiltie, A. E., ... Chanock, S. J. (2010). A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci. Nature genetics, 42(11), 978-984. https://doi.org/10.1038/ng.687