Genome-wide association study yields variants at 20p12.2 that associate with urinary bladder cancer

• Published in: Human molecular genetics Vol. 23; no. 20; pp. 5545 - 5557
• Main Authors: Rafnar, Thorunn, Sulem, Patrick, Thorleifsson, Gudmar, Vermeulen, Sita H, Helgason, Hannes, Saemundsdottir, Jona, Gudjonsson, Sigurjon A, Sigurdsson, Asgeir, Stacey, Simon N, Gudmundsson, Julius, Johannsdottir, Hrefna, Alexiusdottir, Kristin, Petursdottir, Vigdis, Nikulasson, Sigfus, Geirsson, Gudmundur, Jonsson, Thorvaldur, Aben, Katja K H, Grotenhuis, Anne J, Verhaegh, Gerald W, Dudek, Aleksandra M, Witjes, J Alfred, van der Heijden, Antoine G, Vrieling, Alina, Galesloot, Tessel E, De Juan, Ana, Panadero, Angeles, Rivera, Fernando, Hurst, Carolyn, Bishop, D Timothy, Sak, Sei C, Choudhury, Ananya, Teo, Mark T W, Arici, Cecilia, Carta, Angela, Toninelli, Elena, de Verdier, Petra, Rudnai, Peter, Gurzau, Eugene, Koppova, Kvetoslava, van der Keur, Kirstin A, Lurkin, Irene, Goossens, Mieke, Kellen, Eliane, Guarrera, Simonetta, Russo, Alessia, Critelli, Rossana, Sacerdote, Carlotta, Vineis, Paolo, Krucker, Clémentine, Zeegers, Maurice P, Gerullis, Holger, Ovsiannikov, Daniel, Volkert, Frank, Hengstler, Jan G, Selinski, Silvia, Magnusson, Olafur T, Masson, Gisli, Kong, Augustine, Gudbjartsson, Daniel, Lindblom, Annika, Zwarthoff, Ellen, Porru, Stefano, Golka, Klaus, Buntinx, Frank, Matullo, Giuseppe, Kumar, Rajiv, Mayordomo, José I, Steineck, D Gunnar, Kiltie, Anne E, Jonsson, Eirikur, Radvanyi, François, Knowles, Margaret A, Thorsteinsdottir, Unnur, Kiemeney, Lambertus A, Stefansson, Kari
• Format: Journal Article
• Language: English
• Published: England 15.10.2014
• Subjects: Adult; Aged; Aged, 80 and over; Calcium-Binding Proteins - genetics; Case-Control Studies; Chromosomes, Human, Pair 20 - genetics; Female; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Intercellular Signaling Peptides and Proteins - genetics; Jagged-1 Protein; Male; Medicin och hälsovetenskap; Membrane Proteins - genetics; Middle Aged; Polymorphism, Single Nucleotide; Serrate-Jagged Proteins; Urinary Bladder Neoplasms - genetics; White People - genetics
• ISSN: 0964-6906; 1460-2083; 1460-2083
• DOI: 10.1093/hmg/ddu264

Genome-wide association studies (GWAS) of urinary bladder cancer (UBC) have yielded common variants at 12 loci that associate with risk of the disease. We report here the results of a GWAS of UBC including 1670 UBC cases and 90 180 controls, followed by replication analysis in additional 5266 UBC cases and 10 456 controls. We tested a dataset containing 34.2 million variants, generated by imputation based on whole-genome sequencing of 2230 Icelanders. Several correlated variants at 20p12, represented by rs62185668, show genome-wide significant association with UBC after combining discovery and replication results (OR = 1.19, P = 1.5 × 10(-11) for rs62185668-A, minor allele frequency = 23.6%). The variants are located in a non-coding region approximately 300 kb upstream from the JAG1 gene, an important component of the Notch signaling pathways that may be oncogenic or tumor suppressive in several forms of cancer. Our results add to the growing number of UBC risk variants discovered through GWAS.