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.

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

GUARRERA, Simonetta;RUSSO, ALESSIA;CRITELLI, ROSSANA;SACERDOTE, Carlotta;VINEIS, Paolo;MATULLO, Giuseppe;
2014-01-01

Abstract

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.
2014
23
20
5545
5557
http://www.ncbi.nlm.nih.gov/pubmed
bladder cancer; GWAS
Rafnar T;Sulem P;Thorleifsson G;Vermeulen SH;Helgason H;Saemundsdottir J;Gudjonsson SA;Sigurdsson A;Stacey SN;Gudmundsson J;Johannsdottir H;Alexiusdottir K;Petursdottir V;Nikulasson S;Geirsson G;Jonsson T;Aben KK;Grotenhuis AJ;Verhaegh GW;Dudek AM;Witjes JA;van der Heijden AG;Vrieling A;Galesloot TE;De Juan A;Panadero A;Rivera F;Hurst C;Bishop DT;Sak SC;Choudhury A;Teo MT;Arici C;Carta A;Toninelli E;de Verdier P;Rudnai P;Gurzau E;Koppova K;van der Keur KA;Lurkin I;Goossens M;Kellen E;Guarrera S;Russo A;Critelli R;Sacerdote C;Vineis P;Krucker C;Zeegers MP;Gerullis H;Ovsiannikov D;Volkert F;Hengstler JG;Selinski S;Magnusson OT;Masson G;Kong A;Gudbjartsson D;Lindblom A;Zwarthoff E;Porru S;Golka K;Buntinx F;Matullo G;Kumar R;Mayordomo JI;Steineck DG;Kiltie AE;Jonsson E;Radvanyi F;Knowles MA;Thorsteinsdottir U;Kiemeney LA;Stefansson K
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/157417
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