Genome-wide association study identifies multiple loci associated with bladder cancer risk

Jonine D. Figueroa, Yuanqing Ye, Afshan Siddiq, Montserrat Garcia-closas, Nilanjan Chatterjee, Ludmila Prokunina-olsson, Victoria K. Cortessis, Charles Kooperberg, Olivier Cussenot, Simone Benhamou, Jennifer Prescott, Stefano Porru, Colin P. Dinney, Núria Malats, Dalsu Baris, Mark Purdue, Eric J. Jacobs, Demetrius Albanes, Zhaoming Wang, Xiang DengCharles C. Chung, Wei Tang, H. Bas bueno-de-mesquita, Dimitrios Trichopoulos, Börje Ljungberg, Françoise Clavel-chapelon, Elisabete Weiderpass, Vittorio Krogh, Miren Dorronsoro, Ruth Travis, Anne Tjønneland, Paul Brenan, Jenny Chang-claude, Elio Riboli, David Conti, Manuela Gago-dominguez, Mariana C. Stern, Malcolm C. Pike, David Van den berg, Jian Min Yuan, Chancellor Hohensee, Rebecca Rodabough, Geraldine Cancel-tassin, Morgan Roupret, Eva Comperat, Constance Chen, Immaculata De vivo, Edward Giovannucci, David J. Hunter, Peter Kraft, Sara Lindstrom, Angela Carta, Sofia Pavanello, Cecilia Arici, Giuseppe Mastrangelo, Ashish M. Kamat, Seth P. Lerner, H. Barton grossman, Jie Lin, Jian Gu, Xia Pu, Amy Hutchinson, Laurie Burdette, William Wheeler, Manolis Kogevinas, Adonina Tardón, Consol Serra, Alfredo Carrato, Reina García-closas, Josep Lloreta, Molly Schwenn, Margaret R. Karagas, Alison Johnson, Alan Schned, Karla R. Armenti, G. M. Hosain, Gerald Andriole, Robert Grubb, Amanda Black, W. Ryan Diver, Susan M. Gapstur, Stephanie J. Weinstein, Jarmo Virtamo, Chris A. Haiman, Maria T. Landi, Neil Caporaso, Joseph F. Fraumeni, Paolo Vineis, Xifeng Wu, Debra T. Silverman, Stephen Chanock, Nathaniel Rothman

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Abstract

Candidate gene and genome-wide association studies (GWAS) have identified 11 independent susceptibility loci associated with bladder cancer risk. To discover additional risk variants, we conducted a new GWAS of 2422 bladder cancer cases and 5751 controls, followed by a meta-analysis with two independently published bladder cancer GWAS, resulting in a combined analysis of 6911 cases and 11 814 controls of European descent. TaqMan genotyping of 13 promising single nucleotide polymorphisms with P <1 × 10-5 was pursued in a follow-up set of 801 cases and 1307 controls. Two new loci achieved genome-wide statistical significance: rs10936599 on 3q26.2 (P = 4.53 × 10-9) and rs907611 on 11p15.5 (P = 4.11 × 10-8). Two notable loci were also identified that approached genome-wide statistical significance: rs6104690 on 20p12.2 (P = 7.13 × 10-7) and rs4510656 on 6p22.3 (P = 6.98 × 10-7); these require further studies for confirmation. In conclusion, our study has identified new susceptibility alleles for bladder cancer risk that require fine-mapping and laboratory investigation, which could further understanding into the biological underpinnings of bladder carcinogenesis.

Original languageEnglish
Article numberddt519
JournalHuman Molecular Genetics
Volume23
Issue number5
DOIs
Publication statusPublished - Mar 2014

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ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)
  • Molecular Biology

Cite this

Figueroa, J. D., Ye, Y., Siddiq, A., Garcia-closas, M., Chatterjee, N., Prokunina-olsson, L., Cortessis, V. K., Kooperberg, C., Cussenot, O., Benhamou, S., Prescott, J., Porru, S., Dinney, C. P., Malats, N., Baris, D., Purdue, M., Jacobs, E. J., Albanes, D., Wang, Z., ... Rothman, N. (2014). Genome-wide association study identifies multiple loci associated with bladder cancer risk. Human Molecular Genetics, 23(5), [ddt519]. https://doi.org/10.1093/hmg/ddt519