Promoter methylation and gene polymorphism are two independent events in regulation of GSTP1 gene expression

Breast carcinogenesis is a multistep process, involving both genetic and epigenetic modification process of genes, involved in diverse pathways ranging from DNA repair to metabolic processes. This study was undertaken to assess the role of promoter methylation of GSTP1 gene, a member of glutathione-...

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Main Authors: Aaliya Bhat, A Masood, KA Wani, Younus Ahmad Bhat, Bushra Nissar, Nuzhat Shaheen Khan, BA Ganai
Format: Article
Language:English
Published: SAGE Publishing 2017-04-01
Series:Tumor Biology
Online Access:https://doi.org/10.1177/1010428317697563
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author Aaliya Bhat
A Masood
KA Wani
Younus Ahmad Bhat
Bushra Nissar
Nuzhat Shaheen Khan
BA Ganai
author_facet Aaliya Bhat
A Masood
KA Wani
Younus Ahmad Bhat
Bushra Nissar
Nuzhat Shaheen Khan
BA Ganai
author_sort Aaliya Bhat
collection DOAJ
description Breast carcinogenesis is a multistep process, involving both genetic and epigenetic modification process of genes, involved in diverse pathways ranging from DNA repair to metabolic processes. This study was undertaken to assess the role of promoter methylation of GSTP1 gene, a member of glutathione-S-transferase family of enzymes, in relation to its expression, polymorphism, and clinicopathological parameters. Tissue samples were taken from breast cancer patients and paired with their normal adjacent tissues. A total of 51 subjects were studied, in which the frequency of promoter methylation in cancerous tissue was 37.25% as against 11% in the normal tissues ( p  ≤ 0.001). The hypermethylated status of the gene was significantly associated with the loss of the protein expression ( r  = −0.449, p  = 0.001, odds ratio = 7.42, 95% confidence interval = 2.05–26.92). Furthermore, when compared with the clinical parameters, the significant association was found between the promoter hypermethylation and lymph node metastasis ( p  ≤ 0.001), tumor stage ( p  = 0.039), tumor grade ( p  = 0.028), estrogen receptor status ( p  = 0.018), and progesterone receptor status ( p  = 0.046). Our study is the first of its kind in Kashmiri population, which indicates that GSTP1 shows aberrant methylation pattern in the breast cancer with the consequent loss in the protein expression. Furthermore, it also shows that the gene polymorphism (Ile105Val) at codon 105 is not related to the promoter methylation and two are the independent events in breast cancer development.
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spelling doaj-art-116e7b733b6a4c8ca72d0c20867955e92025-08-20T03:15:53ZengSAGE PublishingTumor Biology1423-03802017-04-013910.1177/1010428317697563Promoter methylation and gene polymorphism are two independent events in regulation of GSTP1 gene expressionAaliya Bhat0A Masood1KA Wani2Younus Ahmad Bhat3Bushra Nissar4Nuzhat Shaheen Khan5BA Ganai6Department of Biochemistry, University of Kashmir, IndiaDepartment of Biochemistry, University of Kashmir, IndiaDepartment of Biochemistry, University of Kashmir, IndiaDepartment of Biochemistry, University of Kashmir, IndiaDepartment of Biochemistry, University of Kashmir, IndiaDepartment of Biochemistry, University of Kashmir, IndiaDepartment of Biochemistry, University of Kashmir, IndiaBreast carcinogenesis is a multistep process, involving both genetic and epigenetic modification process of genes, involved in diverse pathways ranging from DNA repair to metabolic processes. This study was undertaken to assess the role of promoter methylation of GSTP1 gene, a member of glutathione-S-transferase family of enzymes, in relation to its expression, polymorphism, and clinicopathological parameters. Tissue samples were taken from breast cancer patients and paired with their normal adjacent tissues. A total of 51 subjects were studied, in which the frequency of promoter methylation in cancerous tissue was 37.25% as against 11% in the normal tissues ( p  ≤ 0.001). The hypermethylated status of the gene was significantly associated with the loss of the protein expression ( r  = −0.449, p  = 0.001, odds ratio = 7.42, 95% confidence interval = 2.05–26.92). Furthermore, when compared with the clinical parameters, the significant association was found between the promoter hypermethylation and lymph node metastasis ( p  ≤ 0.001), tumor stage ( p  = 0.039), tumor grade ( p  = 0.028), estrogen receptor status ( p  = 0.018), and progesterone receptor status ( p  = 0.046). Our study is the first of its kind in Kashmiri population, which indicates that GSTP1 shows aberrant methylation pattern in the breast cancer with the consequent loss in the protein expression. Furthermore, it also shows that the gene polymorphism (Ile105Val) at codon 105 is not related to the promoter methylation and two are the independent events in breast cancer development.https://doi.org/10.1177/1010428317697563
spellingShingle Aaliya Bhat
A Masood
KA Wani
Younus Ahmad Bhat
Bushra Nissar
Nuzhat Shaheen Khan
BA Ganai
Promoter methylation and gene polymorphism are two independent events in regulation of GSTP1 gene expression
Tumor Biology
title Promoter methylation and gene polymorphism are two independent events in regulation of GSTP1 gene expression
title_full Promoter methylation and gene polymorphism are two independent events in regulation of GSTP1 gene expression
title_fullStr Promoter methylation and gene polymorphism are two independent events in regulation of GSTP1 gene expression
title_full_unstemmed Promoter methylation and gene polymorphism are two independent events in regulation of GSTP1 gene expression
title_short Promoter methylation and gene polymorphism are two independent events in regulation of GSTP1 gene expression
title_sort promoter methylation and gene polymorphism are two independent events in regulation of gstp1 gene expression
url https://doi.org/10.1177/1010428317697563
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