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

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. ZeegersRajiv 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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

218 Citations (Scopus)


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 × 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.

Original languageEnglish
Pages (from-to)991-995
Number of pages5
JournalNature Genetics
Issue number9
Publication statusPublished - Sept 2009

Bibliographical note

Funding Information:
The study was partially supported by NIH grants U01 CA 127615 (X.W.), R01 CA 74880 (X.W.), P50 CA 91846 (X.W., C.P.D.), R01 CA 133996 (C.I.A), P42 ES07373 (M.R.K.) and R01 CA 57494 (M.R.K.), R01 CA 131335 (J.G.) and the Kleberg Center for Molecular Markers at MDACC. We thank the genotyping personnel, study coordinators and interviewers for performing experiments and recruiting participants. We are especially thankful for all the study participants who made the population-based research possible.


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