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. 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

doi:10.1038/ng.421

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

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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 language	English (US)
Pages (from-to)	991-995
Number of pages	5
Journal	Nature genetics
Volume	41
Issue number	9
DOIs	https://doi.org/10.1038/ng.421
State	Published - Sep 2009
Externally published	Yes

ASJC Scopus subject areas

Genetics

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Wu, X., Ye, Y., Kiemeney, L. A., Sulem, P., Rafnar, T., Matullo, G., Seminara, D., Yoshida, T., Saeki, N., Andrew, A. S., Dinney, C. P., Czerniak, B., Zhang, Z. F., Kiltie, A. E., Bishop, D. T., Vineis, P., Porru, S., Buntinx, F., Kellen, E., ... 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

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, GB, 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

@article{70ccba48c19147c1af611adae063398c,

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

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.",

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

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.",

year = "2009",

month = sep,

doi = "10.1038/ng.421",

language = "English (US)",

volume = "41",

pages = "991--995",

journal = "Nature genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "9",

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T1 - Genetic variation in the prostate stem cell antigen gene PSCA confers susceptibility to urinary bladder cancer

AU - Wu, Xifeng

AU - Ye, Yuanqing

AU - Kiemeney, Lambertus A.

AU - Sulem, Patrick

AU - Rafnar, Thorunn

AU - Matullo, Giuseppe

AU - Seminara, Daniela

AU - Yoshida, Teruhiko

AU - Saeki, Norihisa

AU - Andrew, Angeline S.

AU - Dinney, Colin P.

AU - Czerniak, Bogdan

AU - Zhang, Zuo Feng

AU - Kiltie, Anne E.

AU - Bishop, D. Timothy

AU - Vineis, Paolo

AU - Porru, Stefano

AU - Buntinx, Frank

AU - Kellen, Eliane

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 B.

AU - Schned, Alan

AU - Guarrera, Simonetta

AU - Polidoro, Silvia

AU - Chang, Shen Chih

AU - Lin, Jie

AU - Chang, David W.

AU - Hale, Katherine S.

AU - Majewski, Tadeusz

AU - Grossman, H. Barton

AU - Thorlacius, Steinunn

AU - Thorsteinsdottir, Unnur

AU - Aben, Katja K.H.

AU - Witjes, J. Alfred

AU - Stefansson, Kari

AU - Amos, Christopher I.

AU - Karagas, Margaret R.

AU - Gu, Jian

N1 - 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.

PY - 2009/9

Y1 - 2009/9

N2 - 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.

AB - 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.

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

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