Association Between Genetic Polymorphisms in the Prostate-Specific Antigen Gene Promoter and Serum Prostate-Specific Antigen Levels

Background: Recent evidence suggests that genetic variation in the promoter of the prostate-specific antigen (PSA) gene may contribute to individual variation in serum PSA levels. However, polymorphisms associated with variations in PSA levels have not been identified. Methods: We used the polymeras...

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Bibliographic Details
Published in:JNCI : Journal of the National Cancer Institute 2003-07, Vol.95 (14), p.1044-1053
Main Authors: Cramer, Scott D., Chang, Bao-Li, Rao, Anuradha, Hawkins, Gregory A., Zheng, S. Lilly, Wade, Wendy N., Cooke, Roger T., Thomas, Leanne N., Bleecker, Eugene R., Catalona, William J., Sterling, David A., Meyers, Deborah A., Ohar, Jill, Xu, Jianfeng
Format: Article
Language:English
Subjects:
Aged
Allelic Imbalance - genetics
Analysis of Variance
beta-Galactosidase - genetics
Biomarkers, Tumor - genetics
Cloning, Molecular
Gene Amplification
Genetic Markers - genetics
Genetics
Genotype
Haplotypes
Humans
Linkage Disequilibrium - genetics
Luciferases - genetics
Male
Medical research
Middle Aged
Polymerase Chain Reaction - methods
Polymorphism, Single Nucleotide
Predictive Value of Tests
Prevalence
Promoter Regions, Genetic - genetics
Prostate cancer
Prostate-Specific Antigen - blood
Prostate-Specific Antigen - genetics
Prostatic Neoplasms - genetics
Prostatic Neoplasms - immunology
Sequence Analysis, DNA
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Summary:Background: Recent evidence suggests that genetic variation in the promoter of the prostate-specific antigen (PSA) gene may contribute to individual variation in serum PSA levels. However, polymorphisms associated with variations in PSA levels have not been identified. Methods: We used the polymerase chain reaction to amplify the promoter region of the PSA genes (nucleotide positions −3873 to −5749 with respect to the start of transcription) of 409 healthy white men at risk for lung disease. Polymerase chain reaction products were sequenced to identify polymorphisms in the PSA gene promoter and to genotype the men for common single nucleotide polymorphisms (SNPs) and were cloned into luciferase reporter constructs to assay PSA promoter activity in human LNCaP prostate cancer cells. Analysis of variance was used to test the association of polymorphism frequencies with mean serum PSA levels. All statistical tests were two-sided. Results: The −4643G/A SNP (G allele) had a 21.2% prevalence and was associated with increases in serum PSA levels (P = .017) and PSA promoter activity (P
ISSN:0027-8874
1460-2105
DOI:10.1093/jnci/95.14.1044