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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

Nyckelord

Alleles

Antigens

Neoplasm

genetics

immunology

Case-Control Studies

Chromosome Mapping

Chromosomes

Human

Pair 8

GPI-Linked Proteins

Gene Frequency

Genes

Reporter

Genetic Predisposition to Disease

Genetic Variation

Genome-Wide Association Study

Haplotypes

Heterozygote

Homozygote

Humans

Linkage Disequilibrium

Logistic Models

Male

Membrane Glycoproteins

genetics

Multivariate Analysis

Mutation

Missense

Neoplasm Proteins

genetics

Polymorphism

Single Nucleotide

Promoter Regions

Genetic

Reproducibility of Results

Urinary Bladder Neoplasms

genetics

immunology

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)