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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 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.

SUBMITTER: Wu X 

PROVIDER: S-EPMC3313685 | biostudies-literature | 2009 Sep

REPOSITORIES: biostudies-literature

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

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

Nature genetics 20090802 9


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  ...[more]

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