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.
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.
Authors: Mark M Pomerantz; Lillian Werner; Wanling Xie; Meredith M Regan; Gwo-Shu Mary Lee; Tong Sun; Carolyn Evan; Gillian Petrozziello; Mari Nakabayashi; William K Oh; Philip W Kantoff; Matthew L Freedman Journal: Cancer Prev Res (Phila) Date: 2011-03-02
Authors: Brian T Helfand; Stacy Loeb; Qiaoyan Hu; Phillip R Cooper; Kimberly A Roehl; Barry B McGuire; Nikola A Baumann; William J Catalona Journal: J Urol Date: 2013-02-27 Impact factor: 7.450
Authors: Scott D Cramer; Jielin Sun; S Lilly Zheng; Jianfeng Xu; Donna M Peehl Journal: Cancer Epidemiol Biomarkers Prev Date: 2008-09 Impact factor: 4.254
Authors: Hemang Parikh; Zuoming Deng; Meredith Yeager; Joseph Boland; Casey Matthews; Jinping Jia; Irene Collins; Ariel White; Laura Burdett; Amy Hutchinson; Liqun Qi; Jennifer A Bacior; Victor Lonsberry; Matthew J Rodesch; Jeffrey A Jeddeloh; Thomas J Albert; Heather A Halvensleben; Timothy T Harkins; Jiyoung Ahn; Sonja I Berndt; Nilanjan Chatterjee; Robert Hoover; Gilles Thomas; David J Hunter; Richard B Hayes; Stephen J Chanock; Laufey Amundadottir Journal: Hum Genet Date: 2009-10-13 Impact factor: 4.132