Genetic polymorphism of the glutathione-S-transferase P1 gene (GSTP1) and susceptibility to prostate cancer in the Kashmiri population

Abstract

ABSTRACT. Glutathione-S-transferase P1 (GSTP1) is a critical enzyme of the phase II detoxification pathway. One of the common functional polymorphisms of GSTP1 is A→G at nucleotide 313, which results in an amino acid substitution (Ile105Val) at the substrate binding site of GSTP1 and reduces catalytic activity of GSTP1. To investigate the GSTP1 Ile105Val genotype frequency in prostate cancer cases in the Kashmiri population, we designed a case-control study, in which 50 prostate cancer cases and 45 benign prostate hyperplasia cases were studied for GSTP1 Ile105Val polymorphism, compared to 80 controls taken from the general population, employing the PCR-RFLP technique. We found the frequency of the three different genotypes of GSTP1 Ile105Val in our ethnic Kashmir population, i.e., Ile/Ile, Ile/ Val and Val/Val, to be 52.4, 33.3 and 14.3% among prostate cancer cases, 48.5, 37.5 and 14% among benign prostate hyperplasia cases and Genetic polymorphism of the GSTP1 gene and prostate cancer 73.8, 21.3 and 5% in the control population, respectively. There was a significant association between the GSTP1 Ile/Val genotype and the advanced age group among the cases. We conclude that GSTP1 Ile/Val polymorphism is involved in the risk of prostate cancer development in our population.

Association of glutathione-S-transferase P1 (GSTP1)-313 A>G gene polymorphism and susceptibility to endometrial hyperplasia among Egyptian women

“…Furthermore, GSTP1 is a key substance in the biotransformation and inactivation of certain environmental pollutant. Due to enzymatic activity of GSTP1-313 A > G polymorphism, GSTP1 may confer susceptibility to several cancers [23,25].…”

“…Genotyping of the GSTP1 Ile105Val gene polymorphism at exon 5 was carried out via the polymerase chain reactionrestriction fragment length polymorphism method (PCR-RFLP), using the forward (5 0 -ACC CCA GGG CTC TAT GGG AA-3 0 ) and reverse (5 0 -TGA GGG CAC AAG AAG CCC CT-3 0 ) primers, which were used to generate a segment of 176 bps of the GSTP1 gene [23]. The PCR amplification was carried out using Veriti Ò Thermal Cycler (Applied Biosystems) in a volume containing about 50 ng genomic DNA template, 200 lM of each dNTP, 200 ng of each primer, 1.5 mM MgCl2, 1· PCR buffer (50 mM KCl, 10 mM Tris-HCl, pH 8.3), and 1 U Taq DNA polymerase.…”

The Role of the Clinical and Molecular Assays in Prostate Cancer Detection

“…There are several important genes such as glutathione-S-transferases (GST) which are involved in DNA repair and protect DNA from damages by detoxifying the carcinogens, metabolism of hormones and chemical agents. Different GST isoform is expressed in the prostate and some tissues [22][23]. Several genetic polymorphisms and total or partial deletions of GST family (GSTM1, GSTT1, GSTM3, GSTPI, and GSTZ1) have been identified that associated with a reduction of enzymatic activity [24].…”

“…This gene is involved in the detoxification of electrophilic carcinogens and has a polymorphic site at codon 105 (exon 5), where (A>G) transition causes an Ile-to-Val substitution. The presence of valine residue to the hydrophobic binding site for electrophilic substrates has been associated with decreased enzyme activity and a tendency to increase neoplasms [22]. Knowledge of GST variation has led to understanding the role of GST family genes in somatic mutation and tumor formation [16].…”

Gene Frequencies of the Human GSTT1 (Null Allele) and GSTP1 (Ile105Val) Polymorphisms among South Indian Populations

“…The well studied functional polymorphism is an A to G transition at nucleotide 313 in exon 5 of GSTP1 gene which results in an isoleucine to valine substitution in codon 105 (Ile105Val) which is located on the substrate-binding site of GSTP1 (Hu et al, 1997). Since the initial identification of GST polymorphisms, a large number of genetic association studies have been conducted to investigate the relationship between these polymorphisms and the risk of disease or treatment outcome (Davies et al, 2001;Mossallam et al, 2006;Qadri et al, 2011). GST gene polymorphisms have also been studied with respect to various cancers and have been variously associated with cervical cancer , esophageal cancer (Yi and Li, 2012), colorectal cancer (Wang et al, 2012), and Hodgkin and non-Hodgkin lymphoma (Bin and Luo, 2013).…”