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- Title
Association Between Genetic Polymorphisms in the Prostate-Specific Antigen Gene Promoter and Serum Prostate-Specific Antigen Levels.
- Authors
Cramer, Scott D.; Bao-Li Chang; Rao, Anuradha; Hawkins, Gregory A.; Zheng, S. Lilly; Wade, Wendy N.; Cooke, Roger T.; Thomas, Leanne N.; Bleecker, Eugene T.; Catalona, William J.; Sterling, David A.
- Abstract
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<.001). The -5412C/T SNP (C allele) had a 22.0% prevalence and was associated with an increase in serum PSA levels (P = .0015). The -5429T/G SNP (G allele) had a 23.0% prevalence, was associated with an increase in serum PSA levels (P = .021), and was in linkage disequilibrium with the -5412C/T SNP. The promoter activity of the -5412 C/-5429 G haplotype was higher than that of the -5412 T/-5429 T haplotype (P<.001). Conclusions: Genetic variations in the PSA promoter are associated with serum PSA levels in men without prostatic disease. PSA promoter genotype information may help to refine models of PSA cutoff values.
- Subjects
GENETIC polymorphisms; PROSTATE-specific antigen; PROMOTERS (Genetics)
- Publication
JNCI: Journal of the National Cancer Institute, 2003, Vol 95, Issue 14, p1044
- ISSN
0027-8874
- Publication type
Article
- DOI
10.1093/jnci/95.14.1044