Identification of a novel susceptibility locus at 13q34 and refinement of the 20p12.2 region as a multi-signal locus associated with bladder cancer risk in individuals of European ancestry
Year: 2016
Type: article
Study design: Observational Study
Abstract: Candidate gene and genome-wide association studies (GWAS) have identified 15 independent genomic regions associated with bladder cancer risk. In search for additional susceptibility variants, we followed up on four promising single-nucleotide polymorphisms (SNPs) that had not achieved genome-wide significance in 6911 cases and 11 814 controls (rs6104690, rs4510656, rs5003154 and rs4907479, P < 1 × 10(-6)), using additional data from existing GWAS datasets and targeted genotyping for studies that did not have GWAS data. In a combined analysis, which included data on up to 15 058 cases and 286 270 controls, two SNPs achieved genome-wide statistical significance: rs6104690 in a gene desert at 20p12.2 (P = 2.19 × 10(-11)) and rs4907479 within the MCF2L gene at 13q34 (P = 3.3 × 10(-10)). Imputation and fine-mapping analyses were performed in these two regions for a subset of 5551 bladder cancer cases and 10 242 controls. Analyses at the 13q34 region suggest a single signal marked by rs4907479. In contrast, we detected two signals in the 20p12.2 region-the first signal is marked by rs6104690, and the second signal is marked by two moderately correlated SNPs (r(2) = 0.53), rs6108803 and the previously reported rs62185668. The second 20p12.2 signal is more strongly associated with the risk of muscle-invasive (T2-T4 stage) compared with non-muscle-invasive (Ta, T1 stage) bladder cancer (case-case P ≤ 0.02 for both rs62185668 and rs6108803). Functional analyses are needed to explore the biological mechanisms underlying these novel genetic associations with risk for bladder cancer.
Source: Human Molecular Genetics
DOI: 10.1093/hmg/ddv492
Authors: Jonine D. Figueroa, Candace D. Middlebrooks, A. Rouf Banday, Yuanqing Ye, Montserrat Garcia-Closas, Nilanjan Chatterjee, Stella Koutros, Lambertus A. Kiemeney, Thorunn Rafnar, Timothy Bishop, Helena Furberg, Giuseppe Matullo, Klaus Golka, Manuela Gago-Dominguez, Jack A. Taylor, Tony Fletcher, Afshan Siddiq, Victoria K. Cortessis, Charles Kooperberg, Olivier Cussenot, Simone Benhamou, Jennifer Prescott, Stefano Porru, Colin P. Dinney, Núria Malats, Dalsu Baris, Mark P. Purdue, Eric J. Jacobs, Demetrius Albanes, Zhaoming Wang, Charles C. Chung, Sita H. Vermeulen, Katja K. Aben, Tessel E. Galesloot, Gudmar Thorleifsson, Patrick Sulem, Kari Stefansson, Anne E. Kiltie, Mark Harland, Mark Teo, Kenneth Offit, Joseph Vijai, Dean Bajorin, Ryan Kopp, Giovanni Fiorito, Simonetta Guarrera, Carlotta Sacerdote, Silvia Selinski, Jan G. Hengstler, Holger Gerullis, Daniel Ovsiannikov, Meinolf Blaszkewicz, Jose Esteban Castelao, Manuel Calaza, Maria Elena Martinez, Patricia Cordeiro, Zongli Xu, Vijayalakshmi Panduri, Rajiv Kumar, Eugene Gurzau, Kvetoslava Koppova, H. Bas Bueno-De-Mesquita, Börje Ljungberg, Françoise Clavel-Chapelon, Elisabete Weiderpass, Vittorio Krogh, Miren Dorronsoro, Ruth C. Travis, Anne Tjønneland, Paul Brennan, Jenny Chang-Claude, Elio Riboli, David Conti, Marianna C. Stern, Malcolm C. Pike, David Van Den Berg, Jian-Min Yuan, Chancellor Hohensee, Rebecca P. Jeppson, Geraldine Cancel-Tassin, Morgan Roupret, Eva Comperat, Constance Turman, Immaculata De Vivo, Edward Giovannucci, David J. Hunter, Peter Kraft, Sara Lindstrom, Angela Carta, Sofia Pavanello, Cecilia Arici, Giuseppe Mastrangelo, Ashish M. Kamat, Liren Zhang, Yilei Gong, Xia Pu, Amy Hutchinson, Laurie Burdett, William A. Wheeler, Margaret R. Karagas, Alison Johnson, Alan Schned, G. M. Monawar Hosain, Molly Schwenn, Manolis Kogevinas, Adonina Tardón, Consol Serra, Alfredo Carrato, Reina García-Closas, Josep Lloreta, Gerald Andriole, Robert Grubb, Amanda Black, W. Ryan Diver, Susan M. Gapstur, Stephanie Weinstein, Jarmo Virtamo, Christopher A. Haiman, Maria Teresa Landi, Neil E. Caporaso, Joseph F. Fraumeni, Paolo Vineis, Xifeng Wu, Stephen J. Chanock, Debra T. Silverman, Ludmila Prokunina-Olsson, Nathaniel Rothman
Institutions: National Cancer Institute, Institute of Genetics and Cancer, Division of Cancer Epidemiology and Genetics, University of Edinburgh, The University of Texas MD Anderson Cancer Center, Institute of Cancer Research, Radboud University Nijmegen, Radboud University Medical Center, Radboud Institute for Health Sciences, deCODE Genetics (Iceland), Italian institute for Genomic Medicine, University of Turin, Leibniz Research Centre for Working Environment and Human Factors, Fundación Pública Galega de Medicina Xenómica, Instituto de Investigación Sanitaria de Santiago, Servicio Gallego de Salud, National Institutes of Health, National Institute of Environmental Health Sciences, London School of Hygiene & Tropical Medicine, University of Southern California, USC Norris Comprehensive Cancer Center, Fred Hutch Cancer Center, Hôpital Tenon, Université Pierre-et-Marie-Curie, Centre National de la Recherche Scientifique, Inserm, Institut Gustave Roussy, Fondation Jean Dausset-CEPH, Variabilité Génétique et Maladies Humaines, Brigham and Women's Hospital, Harvard University, University of Brescia, Spanish National Cancer Research Centre, American Cancer Society, University of Iceland, University of Oxford, CRUK/MRC Oxford Institute for Radiation Oncology, University of Leeds, Memorial Sloan Kettering Cancer Center, Piedmont Reference Center for Epidemiology and Cancer Prevention, Carl von Ossietzky Universität Oldenburg, Klinikum Oldenburg, Lukaskrankenhaus, St. Josefs Hospital, Universidade de Santiago de Compostela, Center for Research in Molecular Medicine and Chronic Diseases, University of California San Diego, Moores Cancer Center, Complejo Hospitalario Universitario de Santiago, German Cancer Research Center, University Medical Center Hamburg-Eppendorf, University Cancer Center Hamburg, Public Health Authority of the Slovak Republic, University of Malaya, National Institute for Public Health and the Environment, Umeå University, Université Paris-Sud, Centre de recherche en Epidémiologie et Santé des Populations, Karolinska Institutet, Cancer Registry of Norway, Folkhälsans Forskningscentrum, UiT The Arctic University of Norway, Fondazione IRCCS Istituto Nazionale dei Tumori, Biogipuzkoa Health Research Institute, Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública, Danish Cancer Society, Centre international de recherche sur le cancer, UPMC Hillman Cancer Center, Pitié-Salpêtrière Hospital, Assistance Publique – Hôpitaux de Paris, Broad Institute, Massachusetts Institute of Technology, University of Padua, Information Management Services, Dartmouth College, New Hampshire Hospital, Center for Research in Environmental Epidemiology, National School of Public Health, Municipal Institute for Medical Research, Hospital del Mar Research Institute, Universidad de Oviedo, Universitat Pompeu Fabra, Instituto Ramón y Cajal de Investigación Sanitaria, Hospital Universitario Ramón y Cajal, Hospital Universitario de Canarias, Washington University in St. Louis, Finnish Institute for Health and Welfare, MRC Centre for Environment and Health, Imperial College London
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2225833867