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 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

Research output: Contribution to journalArticle

190 Citations (Scopus)

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 × 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 (US)
Pages (from-to)991-995
Number of pages5
JournalNature Genetics
Volume41
Issue number9
DOIs
StatePublished - Sep 1 2009
Externally publishedYes

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Urinary Bladder Neoplasms
Single Nucleotide Polymorphism
Prostate
Stem Cells
Antigens
Population
Genes
Initiator Codon
Genome-Wide Association Study
Protein Sorting Signals
Reporter Genes
Alleles
Odds Ratio
Confidence Intervals
Amino Acids

ASJC Scopus subject areas

  • Genetics

Cite this

Wu, X., Ye, Y., Kiemeney, L. A., Sulem, P., Rafnar, T., Matullo, G., ... Gu, J. (2009). Genetic variation in the prostate stem cell antigen gene PSCA confers susceptibility to urinary bladder cancer. Nature Genetics, 41(9), 991-995. https://doi.org/10.1038/ng.421

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

In: Nature Genetics, Vol. 41, No. 9, 01.09.2009, p. 991-995.

Research output: Contribution to journalArticle

Wu, X, Ye, Y, Kiemeney, LA, Sulem, P, Rafnar, T, Matullo, G, Seminara, D, Yoshida, T, Saeki, N, Andrew, AS, Dinney, CP, Czerniak, B, Zhang, ZF, Kiltie, AE, Bishop, DT, Vineis, P, Porru, S, Buntinx, F, Kellen, E, Zeegers, MP, Kumar, R, Rudnai, P, Gurzau, E, Koppova, K, Mayordomo, JI, Sanchez, M, Saez, B, Lindblom, A, De Verdier, P, Steineck, G, Mills, G, Schned, A, Guarrera, S, Polidoro, S, Chang, SC, Lin, J, Chang, DW, Hale, KS, Majewski, T, Grossman, HB, Thorlacius, S, Thorsteinsdottir, U, Aben, KKH, Witjes, JA, Stefansson, K, Amos, CI, Karagas, MR & Gu, J 2009, 'Genetic variation in the prostate stem cell antigen gene PSCA confers susceptibility to urinary bladder cancer', Nature Genetics, vol. 41, no. 9, pp. 991-995. https://doi.org/10.1038/ng.421
Wu, Xifeng ; Ye, Yuanqing ; Kiemeney, Lambertus A. ; Sulem, Patrick ; Rafnar, Thorunn ; Matullo, Giuseppe ; Seminara, Daniela ; Yoshida, Teruhiko ; Saeki, Norihisa ; Andrew, Angeline S. ; Dinney, Colin P. ; Czerniak, Bogdan ; Zhang, Zuo Feng ; Kiltie, Anne E. ; Bishop, D. Timothy ; Vineis, Paolo ; Porru, Stefano ; Buntinx, Frank ; Kellen, Eliane ; Zeegers, Maurice P. ; Kumar, Rajiv ; Rudnai, Peter ; Gurzau, Eugene ; Koppova, Kvetoslava ; Mayordomo, Jose Ignacio ; Sanchez, Manuel ; Saez, Berta ; Lindblom, Annika ; De Verdier, Petra ; Steineck, Gunnar ; Mills, Gordon ; Schned, Alan ; Guarrera, Simonetta ; Polidoro, Silvia ; Chang, Shen Chih ; Lin, Jie ; Chang, David W. ; Hale, Katherine S. ; Majewski, Tadeusz ; Grossman, H. Barton ; Thorlacius, Steinunn ; Thorsteinsdottir, Unnur ; Aben, Katja K.H. ; Witjes, J. Alfred ; Stefansson, Kari ; Amos, Christopher I. ; Karagas, Margaret R. ; Gu, Jian. / Genetic variation in the prostate stem cell antigen gene PSCA confers susceptibility to urinary bladder cancer. In: Nature Genetics. 2009 ; Vol. 41, No. 9. pp. 991-995.
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AU - Zeegers, Maurice P.

AU - Kumar, Rajiv

AU - Rudnai, Peter

AU - Gurzau, Eugene

AU - Koppova, Kvetoslava

AU - Mayordomo, Jose Ignacio

AU - Sanchez, Manuel

AU - Saez, Berta

AU - Lindblom, Annika

AU - De Verdier, Petra

AU - Steineck, Gunnar

AU - Mills, Gordon

AU - Schned, Alan

AU - Guarrera, Simonetta

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AU - Hale, Katherine S.

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