A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci

We conducted a multi-stage, genome-wide association study (GWAS) of bladder cancer with a primary scan of 589,299 single nucleotide polymorphisms (SNPs) in 3,532 cases and 5,120 controls of European descent (5 studies) followed by a replication strategy, which included 8,381 cases and 48,275 control...

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Detalles Bibliográficos
Autores principales: Rothman, Nathaniel, Garcia-Closas, Montserrat, Chatterjee, Nilanjan, Malats, Nuria, Wu, Xifeng, Figueroa, Jonine, Real, Francisco X, Van Den Berg, David, Matullo, Giuseppe, Baris, Dalsu, Thun, Michael, Kiemeney, Lambertus A, Vineis, Paolo, De Vivo, Immaculata, Albanes, Demetrius, Purdue, Mark P, Rafnar, Thorunn, Hildebrandt, Michelle A T, Kiltie, Anne E, Cussenot, Olivier, Golka, Klaus, Kumar, Rajiv, Taylor, Jack A, Mayordomo, Jose I, Jacobs, Kevin B, Kogevinas, Manolis, Hutchinson, Amy, Wang, Zhaoming, Fu, Yi-Ping, Prokunina-Olsson, Ludmila, Burdette, Laurie, Yeager, Meredith, Wheeler, William, Tardón, Adonina, Serra, Consol, Carrato, Alfredo, García-Closas, Reina, Lloreta, Josep, Johnson, Alison, Schwenn, Molly, Karagas, Margaret R, Schned, Alan, Andriole, Gerald, Grubb, Robert, Black, Amanda, Jacobs, Eric J, Diver, W Ryan, Gapstur, Susan M, Weinstein, Stephanie J, Virtamo, Jarmo, Cortessis, Victoria K, Gago-Dominguez, Manuela, Pike, Malcolm C, Stern, Mariana C, Yuan, Jian-Min, Hunter, David, McGrath, Monica, Dinney, Colin P, Czerniak, Bogdan, Chen, Meng, Yang, Hushan, Vermeulen, Sita H, Aben, Katja K, Witjes, J Alfred, Makkinje, Remco R, Sulem, Patrick, Besenbacher, Soren, Stefansson, Kari, Riboli, Elio, Brennan, Paul, Panico, Salvatore, Navarro, Carmen, Allen, Naomi E, Bueno-de-Mesquita, H Bas, Trichopoulos, Dimitrios, Caporaso, Neil, Landi, Maria Teresa, Canzian, Federico, Ljungberg, Borje, Tjonneland, Anne, Clavel-Chapelon, Francoise, Bishop, David T, Teo, Mark T W, Knowles, Margaret A, Guarrera, Simonetta, Polidoro, Silvia, Ricceri, Fulvio, Sacerdote, Carlotta, Allione, Alessandra, Cancel-Tassin, Geraldine, Selinski, Silvia, Hengstler, Jan G, Dietrich, Holger, Fletcher, Tony, Rudnai, Peter, Gurzau, Eugen, Koppova, Kvetoslava, Bolick, Sophia C E, Godfrey, Ashley, Xu, Zongli, Sanz-Velez, José I, García-Prats, María D, Sanchez, Manuel, Valdivia, Gabriel, Porru, Stefano, Benhamou, Simone, Hoover, Robert N, Fraumeni, Joseph F, Silverman, Debra T, Chanock, Stephen J
Formato: Texto
Lenguaje:English
Publicado: 2010
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3049891/
https://www.ncbi.nlm.nih.gov/pubmed/20972438
http://dx.doi.org/10.1038/ng.687
Descripción
Sumario:We conducted a multi-stage, genome-wide association study (GWAS) of bladder cancer with a primary scan of 589,299 single nucleotide polymorphisms (SNPs) in 3,532 cases and 5,120 controls of European descent (5 studies) followed by a replication strategy, which included 8,381 cases and 48,275 controls (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 previous GWAS 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)), as well as demonstrated smoking interactions with both regions. Our findings on common variants associated with bladder cancer risk should provide new insights into mechanisms of carcinogenesis.

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