Genetic variation in the prostate stem cell antigen gene PSCA confers susceptibility to urinary bladder cancer View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2009-09

AUTHORS

Xifeng Wu, Yuanqing Ye, Lambertus A Kiemeney, Patrick Sulem, Thorunn Rafnar, Giuseppe Matullo, Daniela Seminara, Teruhiko Yoshida, Norihisa Saeki, Angeline S Andrew, Colin P Dinney, Bogdan Czerniak, Zuo-feng Zhang, Anne E Kiltie, D Timothy Bishop, Paolo Vineis, Stefano Porru, Frank Buntinx, Eliane Kellen, Maurice P Zeegers, Rajiv Kumar, Peter Rudnai, Eugene Gurzau, Kvetoslava Koppova, Jose Ignacio Mayordomo, Manuel Sanchez, Berta Saez, Annika Lindblom, Petra de Verdier, Gunnar Steineck, Gordon B Mills, Alan Schned, Simonetta Guarrera, Silvia Polidoro, Shen-Chih Chang, Jie Lin, David W Chang, Katherine S Hale, Tadeusz Majewski, H Barton Grossman, Steinunn Thorlacius, Unnur Thorsteinsdottir, Katja K H Aben, J Alfred Witjes, Kari Stefansson, Christopher I Amos, Margaret R Karagas, Jian Gu

ABSTRACT

We conducted a genome-wide association study on 969 bladder cancer cases and 957 controls from Texas. For fast-track validation, we evaluated 60 SNPs in three additional US populations and validated the top SNP in nine European populations. A missense variant (rs2294008) in the PSCA gene showed consistent association with bladder cancer in US and European populations. Combining all subjects (6,667 cases, 39,590 controls), the overall P-value was 2.14 x 10(-10) and the allelic odds ratio was 1.15 (95% confidence interval 1.10-1.20). rs2294008 alters the start codon and is predicted to cause truncation of nine amino acids from the N-terminal signal sequence of the primary PSCA translation product. In vitro reporter gene assay showed that the variant allele significantly reduced promoter activity. Resequencing of the PSCA genomic region showed that rs2294008 is the only common missense SNP in PSCA. Our data identify rs2294008 as a new bladder cancer susceptibility locus. More... »

PAGES

991-995

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/ng.421

DOI

http://dx.doi.org/10.1038/ng.421

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1005840846

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/19648920


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