Linked Life Data

12010858

Source:http://linkedlifedata.com/resource/pubmed/id/12010858

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2002-5-15
pubmed:abstractText
The GSTP1 gene encodes for an enzyme, glutathione S-transferase pi (GSTpi),involved in detoxification of carcinogens. An aminoacid substitution (I105V) in GSTP1 produces a variant enzyme with lower activity and less capability of effective detoxification. This variant GSTP*B allele has been associated with a propensity to develop several neoplasms. Because GSTP1 promoter hypermethylation and inactivation of GSTpi expression is a frequent alteration in prostate carcinoma, we hypothesized that this somatic epigenetic modification could obviate any reduced enzyme activity caused by the germ-line polymorphism. We tested for the GSTP1 genotype in a population of prostate cancer patients, and in a control group composed of patients with benign prostatic hyperplasia (BPH) and healthy blood donors. Tissue samples from the 105 prostate cancer cases (105 adenocarcinomas and 34 prostatic intraepithelial neoplasia lesions), and from 43 BPH patients were tested for GSTP1 hypermethylation by methylation-specific PCR. GSTpi protein expression was assessed by immunohistochemistry. No significant effect on prostate cancer risk was detectable for GSTP1 genotype compared with the control population (odds ratio, 1.02; 95% confidence interval, 0.59-1.75). Moreover, no association was found between this genotype and tumor or BPH methylation status. Patients with unmethylated carcinomas did not disclose significant differences in genotypic distribution compared with the control population. In adenocarcinoma, a strong association (P < 0.00001) between GSTP1 promoter hypermethylation and loss of GSTpi expression was observed; however, this trend was not retained in prostatic intraepithelial neoplasia or BPH lesions. Although the GSTP1 polymorphism is not associated with altered susceptibility to prostate cancer, somatic promoter hypermethylation is an effective, but not the only, cause of decreased GSTpi function.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1055-9965
pubmed:author
pubmed:issnType
Print
pubmed:volume
11
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
445-50
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:12010858-Adenocarcinoma, pubmed-meshheading:12010858-Aged, pubmed-meshheading:12010858-Aged, 80 and over, pubmed-meshheading:12010858-Case-Control Studies, pubmed-meshheading:12010858-DNA Methylation, pubmed-meshheading:12010858-Diagnosis, Differential, pubmed-meshheading:12010858-Gene Expression Regulation, Enzymologic, pubmed-meshheading:12010858-Gene Expression Regulation, Neoplastic, pubmed-meshheading:12010858-Genetic Predisposition to Disease, pubmed-meshheading:12010858-Genotype, pubmed-meshheading:12010858-Glutathione S-Transferase pi, pubmed-meshheading:12010858-Glutathione Transferase, pubmed-meshheading:12010858-Humans, pubmed-meshheading:12010858-Immunohistochemistry, pubmed-meshheading:12010858-Isoenzymes, pubmed-meshheading:12010858-Male, pubmed-meshheading:12010858-Middle Aged, pubmed-meshheading:12010858-Neoplasm Staging, pubmed-meshheading:12010858-Polymorphism, Genetic, pubmed-meshheading:12010858-Promoter Regions, Genetic, pubmed-meshheading:12010858-Prostatic Hyperplasia, pubmed-meshheading:12010858-Prostatic Neoplasms, pubmed-meshheading:12010858-Tumor Markers, Biological
pubmed:year
2002
pubmed:articleTitle
I105V polymorphism and promoter methylation of the GSTP1 gene in prostate adenocarcinoma.
pubmed:affiliation
Department of Pathology, Portuguese Institute of Oncology, 4200-072 Porto, Portugal. carmenjeronimo@netc.jp
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't