1. 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
- Author
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Núria Malats, Robert L. Grubb, Jarmo Virtamo, William Wheeler, Zhaoming Wang, Françoise Clavel-Chapelon, Helena Furberg, Colin P.N. Dinney, Stephanie J. Weinstein, Josep Lloreta, Edward Giovannucci, Jan G. Hengstler, Katja K.H. Aben, Manolis Kogevinas, Simonetta Guarrera, Paul Brennan, Joseph Vijai, Alison Johnson, Paolo Vineis, Consol Serra, Mark P. Purdue, Peter Kraft, Vijayalakshmi Panduri, Morgan Rouprêt, Anne Tjønneland, Angela Carta, Geraldine Cancel-Tassin, Thorunn Rafnar, Marianna C. Stern, Molly Schwenn, Silvia Selinski, Giuseppe Matullo, H. Bas Bueno-de-Mesquita, Ruth C. Travis, Jennifer Prescott, Rebecca P. Jeppson, Stephen J. Chanock, Kvetoslava Koppova, David Van Den Berg, Stella Koutros, Amanda Black, Immaculata De Vivo, Stefano Porru, Jack A. Taylor, Laurie Burdett, Alfredo Carrato, Anne E. Kiltie, Timothy Bishop, Ludmila Prokunina-Olsson, Xia Pu, Charles Kooperberg, Reina García-Closas, Charles C. Chung, Cecilia Arici, Debra T. Silverman, W. Ryan Diver, Christopher A. Haiman, Eugene Gurzau, A. Rouf Banday, Amy Hutchinson, Mark Teo, Lambertus A. Kiemeney, Dalsu Baris, Kari Stefansson, Vittorio Krogh, Elio Riboli, Jose E. Castelao, Mark Harland, Victoria K. Cortessis, Chancellor Hohensee, Gerald L. Andriole, Demetrius Albanes, Margaret R. Karagas, Jonine D. Figueroa, Alan R. Schned, Joseph F. Fraumeni, Yilei Gong, Olivier Cussenot, Montserrat Garcia-Closas, Adonina Tardón, Manuela Gago-Dominguez, Simone Benhamou, Candace D. Middlebrooks, Patrick Sulem, Zongli Xu, Ashish M. Kamat, Giovanni Fiorito, Nilanjan Chatterjee, Tessel E. Galesloot, Sara Lindström, Eva Comperat, Kenneth Offit, Giuseppe Mastrangelo, Malcolm C. Pike, Ryan P. Kopp, Eric J. Jacobs, Holger Gerullis, G. M. Monawar Hosain, Gudmar Thorleifsson, Elisabete Weiderpass, Maria Elena Martinez, Constance Turman, Börje Ljungberg, David V. Conti, Patricia Cordeiro, Jenny Chang-Claude, David J. Hunter, Meinolf Blaszkewicz, Sita H. Vermeulen, Carlotta Sacerdote, Nathaniel Rothman, Xifeng Wu, Dean F. Bajorin, Jian-Min Yuan, Maria Teresa Landi, Susan M. Gapstur, Manuel Calaza, Sofia Pavanello, Yuanqing Ye, Tony Fletcher, Liren Zhang, Afshan Siddiq, Neil E. Caporaso, Miren Dorronsoro, Rajiv Kumar, Klaus Golka, and Daniel Ovsiannikov
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0301 basic medicine ,Male ,Candidate gene ,Linkage disequilibrium ,Chromosomes, Human, Pair 20 ,Genome-wide association study ,RECOMBINATION HOTSPOTS ,Linkage Disequilibrium ,Risk Factors ,Molecular Biology ,Genetics ,Genetics (clinical) ,CONFERS SUSCEPTIBILITY ,Genetics & Heredity ,Association Studies Articles ,GENETIC-VARIATION ,General Medicine ,11 Medical And Health Sciences ,NAT2 SLOW ACETYLATION ,Urological cancers Radboud Institute for Health Sciences [Radboudumc 15] ,GSTM1 NULL ,Female ,SMOKING ,Life Sciences & Biomedicine ,Biochemistry & Molecular Biology ,European Continental Ancestry Group ,Locus (genetics) ,Single-nucleotide polymorphism ,Biology ,Polymorphism, Single Nucleotide ,White People ,03 medical and health sciences ,medicine ,Biomarkers, Tumor ,Humans ,Genetic Predisposition to Disease ,GENOME-WIDE ASSOCIATION ,Genetic Association Studies ,METAANALYSIS ,Genetic association ,Bladder cancer ,Science & Technology ,Chromosomes, Human, Pair 13 ,06 Biological Sciences ,medicine.disease ,NUCLEOTIDE EXCHANGE FACTOR ,030104 developmental biology ,Urinary Bladder Neoplasms ,SEQUENCE VARIANT ,Case-Control Studies ,Imputation (genetics) ,Genome-Wide Association Study - Abstract
Contains fulltext : 167299.pdf (Publisher’s version ) (Closed access) 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 x 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 x 10(-11)) and rs4907479 within the MCF2L gene at 13q34 (P = 3.3 x 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
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- 2015