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

2010; Nature Portfolio; Volume: 42; Issue: 11 Linguagem: Inglês

10.1038/ng.687

1546-1718

Nathaniel Rothman, Montserrat García‐Closas, Nilanjan Chatterjee, Núria Malats, Xifeng Wu, Jonine D. Figueroa, Francisco X. Real, David Van Den Berg, Giuseppe Matullo, Dalsu Baris, Michael J. Thun, Lambertus A. Kiemeney, Paolo Vineis, Immaculata De Vivo, Demetrius Albanes, Mark P. Purdue, Þórunn Rafnar, Michelle A.T. Hildebrandt, Anne E. Kiltie, Olivier Cussenot, Klaus Golka, Rajiv Kumar, Jack A. Taylor, José Mayordomo, Kevin B. Jacobs, Manolis Kogevinas, Amy Hutchinson, Zhaoming Wang, Yi‐Ping Fu, Ludmila Prokunina‐Olsson, Laurie Burdett, Meredith Yeager, William Wheeler, Adonina Tardón, Cònsol Serra, Alfredo Carrato, Reina García-Closas, Josep Lloreta, Alison Johnson, Molly Schwenn, Margaret R. Karagas, Alan R. Schned, Gerald L. Andriole, Robert L. 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 McGrath, Colin P. Dinney, Bogdan Czerniak, Meng Chen, Hushan Yang, Sita H. Vermeulen, Katja K.H. Aben, J.A. Witjes, Remco R. Makkinje, Patrick Sulem, Søren Besenbacher, Kári Stéfansson, Elio Ríboli, Paul Brennan, Salvatore Panico, Carmen Navarro, Naomi E. Allen, H. Bas Bueno-de-Mesquita, Dimitrios Trichopoulos, Neil E. Caporaso, Maria Teresa Landi, Federico Canzian, Börje Ljungberg, Anne Tjønneland, Françoise Clavel‐Chapelon, D. Timothy Bishop, Mark Teo, Margaret A. Knowles, Simonetta Guarrera, Silvia Polidoro, Fulvio Ricceri, Carlotta Sacerdote, Alessandra Allione, Géraldine Cancel‐Tassin, Silvia Selinski, Jan G. Hengstler, H. Dietrich, Tony Fletcher, Péter Rudnai, Eugen Gurzău, Kvetoslava Koppová, Sophia C.E. Bolick, Ashley C. Godfrey, Zongli Xu, José I Sanz-Velez, María Dolores García-Prats, Manuel Sanchez, Gabriel Valdivia, Stefano Porru, Simone Benhamou, Robert N. Hoover, Joseph F. Fraumeni, Debra T. Silverman, Stephen J. Chanock,

Genetic Associations and Epidemiology

Montserrat Garcia-Closas and colleagues report a genome-wide association study for bladder cancer. They identify three new susceptibility loci on chromosomes 22q13.1, 19q12 and 2q37.1. We conducted a multi-stage, genome-wide association study of bladder 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 followed by a replication strategy, which included 8,382 cases and 48,275 controls from 16 studies. In a combined analysis, we identified three new regions associated with bladder 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 CCNE1 and rs11892031 (P = 1 × 10−7) maps to the UGT1A cluster on 2q37.1. We confirmed four previously identified genome-wide associations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate associations 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 common variants associated with bladder cancer risk should provide new insights into the mechanisms of carcinogenesis.