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; +100 more... Michael Thun; Lambertus A Kiemeney; Paolo Vineis; Immaculata De Vivo; Demetrius Albanes; Mark P Purdue; Thorunn Rafnar; Michelle AT Hildebrandt; Anne E Kiltie; Olivier Cussenot; Klaus Golka; Rajiv Kumar; Jack A Taylor; Jose I Mayordomo; Kevin B Jacobs; Manolis Kogevinas; Amy Hutchinson; Zhaoming Wang; Yi-Ping Fu; Ludmila Prokunina-Olsson; Laurie Burdett; Meredith Yeager; William Wheeler; Adonina Tardón; Consol Serra; Alfredo Carrato; Reina García-Closas; Josep Lloreta; 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 McGrath; Colin P Dinney; Bogdan Czerniak; Meng Chen; Hushan Yang; Sita H Vermeulen; Katja K Aben; J Alfred Witjes; Remco R Makkinje; 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 TW 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 CE 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; (2010) A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci. Nature genetics, 42 (11). pp. 978-984. ISSN 1061-4036 DOI: 10.1038/ng.687

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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.