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-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 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

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)978-84
Number of pages7
JournalNature Genetics
Volume42
Issue number11
DOIs
Publication statusPublished - Nov 2010

Keywords / Materials (for Non-textual outputs)

  • Arylamine N-Acetyltransferase
  • Chromosome Mapping
  • Chromosomes, Human, Pair 18
  • Chromosomes, Human, Pair 2
  • Chromosomes, Human, Pair 22
  • Europe
  • Family
  • Female
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Humans
  • Incidence
  • Male
  • Neoplasm Staging
  • Polymorphism, Single Nucleotide
  • Risk Assessment
  • Risk Factors
  • Sex Characteristics
  • Smoking
  • Spain
  • United States
  • Urinary Bladder Neoplasms

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