Document Detail


PSA and androgen-related gene (AR, CYP17, and CYP19) polymorphisms and the risk of adenocarcinoma at prostate biopsy.
MedLine Citation:
PMID:  18491956     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The aim of the present study was to examine the impact of polymorphisms in prostate-specific antigen (PSA) and androgen-related genes (AR, CYP17, and CYP19) on prostate cancer (PCa) risk in selected high-risk patients who underwent prostate biopsy. Blood samples and prostate tissues were obtained for DNA analysis. Single-nucleotide polymorphisms in the 50-untranslated regions (UTRs) of the PSA (substitution A>G at position-158) and CYP17 (substitution T>C at 50-UTR) genes were detected by polymerase chain reaction (PCR)-restriction fragment length polymorphism assays. The CAG and TTTA repeats in the AR and CYP19 genes, respectively, were genotyped by PCR-based GeneScan analysis. Patients with the GG genotype of the PSA gene had a higher risk of PCa than those with the AG or AA genotype (OR=3.79, p=0.00138). The AA genotype was associated with lower PSA levels (6.44 +/- 1.64 ng=mL) compared with genotypes having at least one G allele (10.44 +/- 10.06 ng=mL) ( p=0.0687, 95% CI=0.3146 to 8.315, unpaired t-test). The multivariate analysis confirmed the association between PSA levels and PSA genotypes (AA vs. AG+ GG; chi2=0.0482) and CYP19 (short alleles homozygous vs. at least one long allele; chi2=0.0110) genotypes. Genetic instability at the AR locus leading to somatic mosaicism was detected in one PCa patient by comparing the length of AR CAG repeats in matched peripheral blood and prostate biopsy cores. Taken together, these findings suggest that the PSA genotype should be a clinically relevant biomarker to predict the PCa risk.
Authors:
Rodrigo Mattos dos Santos; Carlos Márcio Nóbrega de Jesus; José Carlos Souza Trindade Filho; José Carlos Souza Trindade; João Lauro Viana de Camargo; Cláudia Aparecida Rainho; Silvia Regina Rogatto
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  DNA and cell biology     Volume:  27     ISSN:  1557-7430     ISO Abbreviation:  DNA Cell Biol.     Publication Date:  2008 Sep 
Date Detail:
Created Date:  2008-09-05     Completed Date:  2008-09-16     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9004522     Medline TA:  DNA Cell Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  497-503     Citation Subset:  IM    
Affiliation:
Institute of Biosciences, Sao Paulo State University, UNESP, Botucatu, Sao Paulo, Brazil.
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MeSH Terms
Descriptor/Qualifier:
Adenocarcinoma / genetics*
Aged
Aged, 80 and over
Androgens / metabolism
Aromatase / genetics
Biopsy
Case-Control Studies
Humans
Male
Middle Aged
Polymorphism, Genetic
Prostate / pathology
Prostate-Specific Antigen / genetics*
Prostatic Neoplasms / genetics*
Receptors, Androgen / genetics
Steroid 17-alpha-Hydroxylase / genetics
Chemical
Reg. No./Substance:
0/Androgens; 0/Receptors, Androgen; EC 1.14.14.1/Aromatase; EC 1.14.99.9/Steroid 17-alpha-Hydroxylase; EC 3.4.21.77/Prostate-Specific Antigen

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