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 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.
authors: Xifeng
authors: X
authors: Wu
authors: Yuanqing
authors: Y
authors: Ye
authors: Lambertus A
authors: LA
authors: Kiemeney
authors: Patrick
authors: P
authors: Sulem
authors: Thorunn
authors: T
authors: Rafnar
authors: Giuseppe
authors: G
authors: Matullo
authors: Daniela
authors: D
authors: Seminara
authors: Teruhiko
authors: T
authors: Yoshida
authors: Norihisa
authors: N
authors: Saeki
authors: Angeline S
authors: AS
authors: Andrew
authors: Colin P
authors: CP
authors: Dinney
authors: Bogdan
authors: B
authors: Czerniak
authors: Zuo-feng
authors: ZF
authors: Zhang
authors: Anne E
authors: AE
authors: Kiltie
authors: D Timothy
authors: DT
authors: Bishop
authors: Paolo
authors: P
authors: Vineis
authors: Stefano
authors: S
authors: Porru
authors: Frank
authors: F
authors: Buntinx
authors: Eliane
authors: E
authors: Kellen
authors: Maurice P
authors: MP
authors: Zeegers
authors: Rajiv
authors: R
authors: Kumar
authors: Peter
authors: P
authors: Rudnai
authors: Eugene
authors: E
authors: Gurzau
authors: Kvetoslava
authors: K
authors: Koppova
authors: Jose Ignacio
authors: JI
authors: Mayordomo
authors: Manuel
authors: M
authors: Sanchez
authors: Berta
authors: B
authors: Saez
authors: Annika
authors: A
authors: Lindblom
authors: Petra
authors: P
authors: de Verdier
authors: Gunnar
authors: G
authors: Steineck
authors: Gordon B
authors: GB
authors: Mills
authors: Alan
authors: A
authors: Schned
authors: Simonetta
authors: S
authors: Guarrera
authors: Silvia
authors: S
authors: Polidoro
authors: Shen-Chih
authors: SC
authors: Chang
authors: Jie
authors: J
authors: Lin
authors: David W
authors: DW
authors: Chang
authors: Katherine S
authors: KS
authors: Hale
authors: Tadeusz
authors: T
authors: Majewski
authors: H Barton
authors: HB
authors: Grossman
authors: Steinunn
authors: S
authors: Thorlacius
authors: Unnur
authors: U
authors: Thorsteinsdottir
authors: Katja K H
authors: KK
authors: Aben
authors: J Alfred
authors: JA
authors: Witjes
authors: Kari
authors: K
authors: Stefansson
authors: Christopher I
authors: CI
authors: Amos
authors: Margaret R
authors: MR
authors: Karagas
authors: Jian
authors: J
authors: Gu
mesh_terms: D000483:Alleles; D000951:Antigens, Neoplasm / Q000235:genetics* / Q000276:immunology; D016022:Case-Control Studies; D002874:Chromosome Mapping; D002898:Chromosomes, Human, Pair 8; D058851:GPI-Linked Proteins; D005787:Gene Frequency; D017930:Genes, Reporter; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006239:Haplotypes; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D015810:Linkage Disequilibrium; D016015:Logistic Models; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D015999:Multivariate Analysis; D020125:Mutation, Missense; D009363:Neoplasm Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D015203:Reproducibility of Results; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000276:immunology
chemical_list: D000951:Antigens, Neoplasm; D058851:GPI-Linked Proteins; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; C110843:PSCA protein, human