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

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.

Ye, Yuanqing (author)
Kiemeney, Lambertus A (author)
Sulem, Patrick (author)
Rafnar, Thorunn (author)
Matullo, Giuseppe (author)
Seminara, Daniela (author)
Yoshida, Teruhiko (author)
Saeki, Norihisa (author)
Andrew, Angeline S (author)
Dinney, Colin P (author)
Czerniak, Bogdan (author)
Zhang, Zuo-Feng (author)
Kiltie, Anne E (author)
Bishop, D Timothy (author)
Vineis, Paolo (author)
Porru, Stefano (author)
Buntinx, Frank (author)
Kellen, Eliane (author)
Zeegers, Maurice P (author)
Kumar, Rajiv (author)
Rudnai, Peter (author)
Gurzau, Eugene (author)
Koppova, Kvetoslava (author)
Mayordomo, Jose Ignacio (author)
Sanchez, Manuel (author)
Saez, Berta (author)
Lindblom, AnnikaKarolinska Institutet (author)
de Verdier, PetraKarolinska Institutet (author)
Steineck, Gunnar,1952Karolinska Institutet,Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper,Institute of Clinical Sciences(Swepub:gu)xstegu (author)
Mills, Gordon B (author)
Schned, Alan (author)
Guarrera, Simonetta (author)
Polidoro, Silvia (author)
Chang, Shen-Chih (author)
LIN, JIE (author)
Chang, David W (author)
Hale, Katherine S (author)
Majewski, Tadeusz (author)
Grossman, H Barton (author)
Thorlacius, Steinunn (author)
Thorsteinsdottir, Unnur (author)
Aben, Katja K H (author)
Witjes, J Alfred (author)
Stefansson, Kari (author)
Amos, Christopher I (author)
Karagas, Margaret R (author)
Gu, Jian (author)
Karolinska InstitutetInstitutionen för kliniska vetenskaper (creator_code:org_t)

In:Nature genetics: Springer Science and Business Media LLC41:9, s. 991-51546-17181061-4036

By the author/editor: Wu, Xifeng; Ye, Yuanqing; Kiemeney, Lamber ...; Sulem, Patrick; Rafnar, Thorunn; Matullo, Giusepp ...; show more...; Seminara, Daniel ...; Yoshida, Teruhik ...; Saeki, Norihisa; Andrew, Angeline ...; Dinney, Colin P; Czerniak, Bogdan; Zhang, Zuo-Feng; Kiltie, Anne E; Bishop, D Timoth ...; Vineis, Paolo; Porru, Stefano; Buntinx, Frank; Kellen, Eliane; Zeegers, Maurice ...; Kumar, Rajiv; Rudnai, Peter; Gurzau, Eugene; Koppova, Kvetosl ...; Mayordomo, Jose ...; Sanchez, Manuel; Saez, Berta; Lindblom, Annika; de Verdier, Petr ...; Steineck, Gunnar ...; Mills, Gordon B; Schned, Alan; Guarrera, Simone ...; Polidoro, Silvia; Chang, Shen-Chih; LIN, JIE; Chang, David W; Hale, Katherine ...; Majewski, Tadeus ...; Grossman, H Bart ...; Thorlacius, Stei ...; Thorsteinsdottir ...; Aben, Katja K H; Witjes, J Alfred; Stefansson, Kari; Amos, Christophe ...; Karagas, Margare ...; Gu, Jian; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Cancer and Oncol ...

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