Gene Summary

Gene:GSTO2; glutathione S-transferase omega 2
Aliases: GSTO 2-2, bA127L20.1
Summary:The protein encoded by this gene is an omega class glutathione S-transferase (GST). GSTs are involved in the metabolism of xenobiotics and carcinogens. Four transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jul 2010]
Databases:OMIM, HGNC, Ensembl, GeneCard, Gene
Protein:glutathione S-transferase omega-2
Source:NCBIAccessed: 31 August, 2019


What does this gene/protein do?
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Pathways:What pathways are this gene/protein implicaed in?
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Cancer Overview

Research Indicators

Publications Per Year (1994-2019)
Graph generated 31 August 2019 using data from PubMed using criteria.

Literature Analysis

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Tag cloud generated 31 August, 2019 using data from PubMed, MeSH and CancerIndex

Specific Cancers (6)

Data table showing topics related to specific cancers and associated disorders. Scope includes mutations and abnormal protein expression.

Note: list is not exhaustive. Number of papers are based on searches of PubMed (click on topic title for arbitrary criteria used).

Latest Publications: GSTO2 (cancer-related)

Radic TM, Coric VM, Pljesa-Ercegovac MS, et al.
Concomitance of Polymorphisms in Glutathione Transferase Omega Genes Is Associated with Risk of Clear Cell Renal Cell Carcinoma.
Tohoku J Exp Med. 2018; 246(1):35-44 [PubMed] Related Publications
Glutathione S-transferases (GSTs), a superfamily of multifunctional enzymes, play an important role in the onset and progression of renal cell carcinoma (RCC). However, novel GST omega class (GSTO), consisting of GSTO1-1 and GSTO2-2 isoenzymes, has not been studied in RCC yet. Two coding single nucleotide polymorphisms (SNPs) supposedly affect their functions: GSTO1*C419A (rs4925) causing alanine to aspartate substitution (*A140D) and GSTO2*A424G (rs156697) causing asparagine to aspartate substitution (*N142D), and have been associated with several neurodegenerative diseases and cancers. Functional relevance of yet another GSTO2 polymorphism, identified at the 5' untranslated (5'UTR) gene region (GSTO2*A183G, rs2297235), has not been clearly discerned so far. Therefore, we aimed to assess the effect of specific GSTO1 and GSTO2 gene variants, independently and in interaction with established risk factors (smoking, obesity and hypertension) on the risk for the most aggressive RCC subtype, the clear cell RCC (ccRCC). Genotyping was performed in 239 ccRCC patients and 350 matched controls, while plasma levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker of oxidative DNA damage, were determined by ELISA. As a result, combined effect of all three variant genotypes exhibited almost 3-fold risk of RCC development. Additionally, this association was confirmed at the haplotype level [variant GSTO1*A/GSTO2*G (rs156697)/GSTO2*G (rs2297235) haplotype], suggesting a potential role of those variants in propensity to RCC. Regarding the gene-environment interactions, variant GSTO2*G (rs156697) homozygous smokers are at higher ccRCC risk. Association in terms of oxidative DNA damage was found for GSTO2 polymorphism in 5'UTR and 8-OHdG. In conclusion, the concomitance of GSTO polymorphisms may influence ccRCC risk.

Wang R, Li J, Zhao Y, et al.
Investigating the therapeutic potential and mechanism of curcumin in breast cancer based on RNA sequencing and bioinformatics analysis.
Breast Cancer. 2018; 25(2):206-212 [PubMed] Related Publications
BACKGROUND: Breast cancer is a prevalent cancer in female. This study aims to investigate the therapeutic potential and mechanism of curcumin in breast cancer.
METHODS: After cultivation, human breast cancer cells (MCF-7 cells) were treated with 0.1% (v/v) 15 µmol/ml curcumin-dimethylsulfoxide solution and 0.1% (v/v) dimethylsulfoxide, respectively, at 37 °C and 5% CO
RESULTS: After DEGs screening, 347 DEGs were identified. Up-regulated DEGs were enriched in 14 functions and 3 pathways, and associated with 12 drugs. Down-regulated DEGs were enriched in 14 functions and 9 pathways, and associated with 14 drugs. Moreover, 5 DEGs were associated with breast cancer, including PGAP3, MAP3K1, SERPINE1, PON2, and GSTO2. PPI network was constructed, and the top DEGs were FOS, VIM, FGF2, MAPK1, SPARC, TOMM7, PSMB10, TCEB2, SOCS1, COL4A1, UQCR11, SERPINE1, and ISG15.
CONCLUSION: Curcumin might have therapeutic potential in breast cancer through regulating breast cancer-related genes, including SERPINE1, PGAP3, MAP3K1, MAPK1, GSTO2, VIM, SPARC, and FGF2. However, validations are required.

Shaban NZ, Salem HH, Elsadany MA, et al.
Distribution of Glutathione S-Transferase Omega Gene Polymorphism with Different Stages of HBV Infection Including Hepatocellular Carcinoma in the Egyptian Population.
Asian Pac J Cancer Prev. 2016; 17(4):2145-50 [PubMed] Related Publications
BACKGROUND: Infection with hepatitis B virus (HBV) is a major global public health problem, with a wide spectrum of clinical manifestations. Human cytosolic glutathione-S-transferases (GSTs) include several classes such as alpha (A), mu (M), pi (P), sigma (S), zeta (Z), omega (O) and theta (T). The present study aimed to investigate the role of GST omega genes (GSTO1 and GSTO2) in different groups of patients infected with HBV.
MATERIALS AND METHODS: HBV groups were classified according to clinical history, serological tests and histological analysis into normal carriers (N), acute (A), chronic (CH), cirrhosis (CI) and hepatocellular carcinoma (HCC) cases. The study focused on determination of the genotypes of GST omega genes (GSTO1 and GSTO2) and GST activity and liver function tests.
RESULTS: The results showed that GSTO1 (A/A) was decreased in N, A, CH, CI and HCC groups compared to the C-group, while, GSTO1 (C/A) and GSTO1(C/C) genotypes were increased significantly in N, A, CH, CI and HCC groups. GSTO2 (A/A) was decreased in all studied groups as compared to the C-group but GSTO2(A/G) and GSTO2(G/G) genotypes were increased significantly. In addition, GST activities, albumin and TP levels were decreased in all studied groups compared to the C-group, while the activities of transaminases were increased to differing degrees.
CONCLUSIONS: The results indicate that GSTO genetic polymorphisms may be considered as biomarkers for determining and predicting the progression of HBV infection.

Qu K, Liu SS, Wang ZX, et al.
Polymorphisms of glutathione S-transferase genes and survival of resected hepatocellular carcinoma patients.
World J Gastroenterol. 2015; 21(14):4310-22 [PubMed] Free Access to Full Article Related Publications
AIM: To investigate the effects of single nucleotide polymorphisms (SNPs) in glutathione S-transferase (GST) genes on survival of hepatocellular carcinoma (HCC) patients.
METHODS: Twelve tagging SNPs in GST genes (including GSTA1, GSTA4, GSTM2, GSTM3, GSTO1, GSTO2 and GSTP1) were genotyped using Sequenom MassARRAY iPLEX genotyping method in a cohort of 214 Chinese patients with resected HCC. The Cox proportional hazards model and log-rank test were performed to determine the SNPs related to outcome. Additionally, stratified analysis was performed at each level of the demographic and clinical variables. An SNP-gene expression association model was further established to investigate the correlation between SNP and gene expression.
RESULTS: Two SNPs (GSTO2: rs7085725 and GSTP1: rs4147581) were significantly associated with overall survival in HCC patients (P = 0.035 and 0.042, respectively). In stratified analysis, they were more significantly associated with overall survival in patients with younger age, male gender and cirrhosis. We further investigated cumulative effects of these two SNPs on overall survival in HCC patients. Compared with the patients carrying no unfavorable genotypes, those carrying 2 unfavorable genotypes had a 1.70-fold increased risk of death (P < 0.001). The cumulative effects were more significant in those patients with younger age, male gender and cirrhosis (HR = 2.00, 1.94 and 1.97, respectively; all P < 0.001). Additionally, we found that heavy smoking resulted in a significantly worse overall survival in those patients carrying variant alleles of rs7085725 (HR = 2.07, 95%CI: 1.13-3.76, P = 0.018). The distributions of GSTO2: rs7085725 and GSTP1: rs4147581 genotypes were associated with altered gene expression and contributed to influences on overall survival.
CONCLUSION: Our study provides the first evidence that GSTO2 and GSTP1 gene polymorphisms may serve as independent prognostic markers for HCC patients.

Wang Z, Qu K, Huang Z, et al.
Glutathione S-transferase O2 gene rs157077 polymorphism predicts response to transarterial chemoembolization in hepatocellular carcinoma.
Tumour Biol. 2015; 36(8):6463-9 [PubMed] Related Publications
Some genetic alterations of glutathione S-transferase omega 2 (GSTO2) have been reported to increase the risk of many malignancies, including hepatocellular carcinoma (HCC); however, their prognostic capability remained unresolved in HCC patients treated with transarterial chemoembolization (TACE). To fill this gap, we genotyped three well-defined polymorphisms in GSTO2 to assess whether they can predict overall survival among 228 HCC patients under TACE treatment. The median follow-up time and survival time were 22.0 months (range 3.0-60.0) and 19.2 months, respectively. Only one of three polymorphisms examined, rs157077, was significantly associated with overall survival of TACE-treated HCC (P = 0.003), and its mutant allele conferred a higher risk of death than its wild homozygotes (hazard ratio 1.58, 95 % confidence interval 1.17-2.14). Moreover, carriers of this mutant allele had higher tissue GSTO2 expression, reinforcing the prognostic capability of GSTO2 rs157077 for HCC, especially in combination with age and tumor-node-metastasis (TNM) stage. Taken together, we for the first time provided evidence supporting the prognostic role of GSTO2 in the progression of TACE-treated HCC.

Rezazadeh D, Moradi MT, Kazemi A, Mansouri K
Childhood Pre-B acute lymphoblastic leukemia and glutathione S-transferase omega 1 and 2 polymorphisms.
Int J Lab Hematol. 2015; 37(4):530-5 [PubMed] Related Publications
INTRODUCTION: Acute lymphoblastic leukemia (ALL) is the most prevalent malignancy among children and makes up 23% of total childhood cancers worldwide. Pre-B ALL is one of the most common ALLs, comprising about 80% of childhood cases. A variety of genes are involved in metabolizing carcinogens. These gene polymorphisms can result in less efficient or overly-down metabolic pathways, which may contribute to the susceptibility to develop cancer. Glutathione S-transferase omega (GSTO) is a new known class among GSTs superfamily. GSTO1 and GSTO2 polymorphisms have been reported to be related to several types of disease. We assessed the association between GSTO1 and GSTO2 polymorphisms and childhood pre-B ALL risk in Iran.
METHODS: This case-control study analyzed GSTO1 A140D (rs. 4925) and GSTO2 N142D (rs. 156697) gene polymorphisms using a polymerase chain reaction-restriction fragment length polymorphism method, in 100 patients and 120 healthy controls.
RESULTS: The genotype frequencies were not significantly different between patients and healthy controls. Odds ratio (95% confidence intervals) for mutant homozygotes were 1.54 (0.628-3.778) and 0.791 (0.349-1.793) for GSTO1 A140D and GSTO2 N142D, respectively.
CONCLUSION: This study found no significant association between Pre-B ALL and GSTO1 A140D and GSTO2 N142D polymorphisms.

Djukic TI, Savic-Radojevic AR, Pekmezovic TD, et al.
Glutathione S-transferase T1, O1 and O2 polymorphisms are associated with survival in muscle invasive bladder cancer patients.
PLoS One. 2013; 8(9):e74724 [PubMed] Free Access to Full Article Related Publications
OBJECTIVE: To examine the association of six glutathione transferase (GST) gene polymorphisms (GSTT1, GSTP1/rs1695, GSTO1/rs4925, GSTO2/rs156697, GSTM1, GSTA1/rs3957357) with the survival of patients with muscle invasive bladder cancer and the genotype modifying effect on chemotherapy.
PATIENTS AND METHODS: A total of 105 patients with muscle invasive bladder cancer were included in the study. The follow-up lasted 5 years. The effect of GSTs polymorphisms on predicting mortality was analyzed by the Cox proportional hazard models, while Kaplan-Meier analysis was performed to assess differences in survival.
RESULTS: GSTT1 active, GSTO1 Asp140Asp or GSTO2 Asp142Asp genotypes were independent predictors of a higher risk of death among bladder cancer patients (HR = 2.5, P = 0.028; HR = 2.9, P = 0.022; HR = 3.9, P = 0.001; respectively) and significantly influenced the overall survival. There was no association between GSTP1, GSTM1 and GSTA1 gene variants with overall mortality. Only GSTO2 polymorphism showed a significant effect on the survival in the subgroup of patients who received chemotherapy (P = 0.006).
CONCLUSION: GSTT1 active genotype and GSTO1 Asp140Asp and GSTO2 Asp142Asp genotypes may have a prognostic/pharmacogenomic role in patients with muscle invasive bladder cancer.

Sohail A, Kanwal N, Ali M, et al.
Effects of glutathione-S-transferase polymorphisms on the risk of breast cancer: a population-based case-control study in Pakistan.
Environ Toxicol Pharmacol. 2013; 35(2):143-53 [PubMed] Related Publications
Cancer is widely accepted as one of the major health issues. Diet composition and exposure to environmental genotoxic and carcinogenic agents such as polycyclic aromatic hydrocarbons (PAHs) are among the causative factors for various types of cancers, including breast cancer. Low penetrance genes including glutathione S transferases (GST) in association with environmental factors can contribute greatly in the development of breast cancer. We were interested to investigate the association of the polymorphisms of GSTM1, GSTT1, GSTP1 and GSTO2 with the risk of breast cancer in the Pakistani population. One hundred women visiting the Department of Radiology and Oncology, Nishter Hospital, Multan with pathologically confirmed breast cancer, and 100 healthy volunteers from central Pakistan were enrolled in the present study. The strength of the association of various factors with breast cancer was measured by calculating odd ratios (ORs) which were determined by logistic regression. All P values cited are two-sided; differences resulting in a P value of less or equal to 0.05 were declared statistically significant. The Hardy Weinberg equilibrium was tested for the genotype proportions in the control group, as a measure of quality control. Those aged 36-45, in menopause or with a history of cancer in the family had a significantly higher prevalence of breast cancer compared with controls. The frequency of GSTM1 and GSTT1 was similar in both control and patients suggesting no association with the risk of cancer development, however GSTM1 and GSTT1 were significantly linked with the risk of breast cancer in smokers and in women with a history of breast cancer in the family respectively. Similarly women homozygous for GSTP1 or GSTO2 and with a history of breast cancer, or in menopause, were at greater risk of breast cancer than wild type or heterozygotes. Our data suggest that genetic differences in some GST genes may be linked with an increased susceptibility to breast cancer. Furthermore it also gives an insight into the interaction between the GST polymorphisms and pre-menopausal diagnosis of breast cancer.

Sanguansin S, Petmitr S, O-Charoenrat P, Pongstaporn W
Association of glutathione S-transferase omega gene polymorphisms with progression of head and neck cancer.
Mol Biol Rep. 2012; 39(12):10915-20 [PubMed] Related Publications
This study investigated the influence of glutathione S-transferase omega 1 (GSTO1) and GSTO2 gene polymorphisms on susceptibility and aggressiveness of head and neck squamous cell carcinoma (HNSCC). A case-control study consisting of 300 HNSCC cases and 299 age and sex- matched normal control was performed. Genotyping of GSTO1*A140D and GSTO2*N142D polymorphisms was determined using the polymerase chain reaction-restriction fragment length polymorphism method. Our results revealed that the frequencies of GSTO1 and GSTO2 genotypes were not significantly different between HNSCC cases and controls. No significant differences were found in smoking or drinking status between cases and controls. However, HNSCC individuals with the GSTO1*D140 varient were significantly associated with nodal metastasis (OR = 0.53, 95 %CI = 0.31-0.91, P = 0.020) and advanced pathological stage (OR = 0.33,95 %CI = 0.15-0.70, P = 0.032), while no significant association was observed between GSTO2 genotype and clinicopathological features. Therefore, our findings suggest that the GSTO1*D140 variant genotype in individuals might play a protective role against the aggressiveness of HNSCC.

Lesseur C, Gilbert-Diamond D, Andrew AS, et al.
A case-control study of polymorphisms in xenobiotic and arsenic metabolism genes and arsenic-related bladder cancer in New Hampshire.
Toxicol Lett. 2012; 210(1):100-6 [PubMed] Free Access to Full Article Related Publications
Arsenic is associated with bladder cancer risk even at low exposure levels. Genetic variation in enzymes involved in xenobiotic and arsenic metabolism may modulate individual susceptibility to arsenic-related bladder cancer. Through a population-based case-control study in NH (832 cases and 1191 controls), we investigated gene-environment interactions between arsenic metabolic gene polymorphisms and arsenic exposure in relation to bladder cancer risk. Toenail arsenic concentrations were used to classify subjects into low and high exposure groups. Single nucleotide polymorphisms (SNPs) in GSTP1, GSTO2, GSTZ1, AQP3, AS3MT and the deletion status of GSTM1 and GSTT1 were determined. We found evidence of genotype-arsenic interactions in the high exposure group; GSTP1 Ile105Val homozygous individuals had an odds ratio (OR) of 5.4 [95% confidence interval (CI): 1.5-20.2; P for interaction=0.03] and AQP3 Phe130Phe carriers had an OR=2.2 (95% CI: 0.8-6.1; P for interaction=0.10). Bladder cancer risk overall was associated with GSTO2 Asn142Asp (homozygous; OR=1.4; 95% CI: 1.0-1.9; P for trend=0.06) and GSTZ1 Glu32Lys (homozygous; OR=1.3; 95% CI: 0.9-1.8; P for trend=0.06). Our findings suggest that susceptibility to bladder cancer may relate to variation in genes involved in arsenic metabolism and oxidative stress response and potential gene-environment interactions requiring confirmation in other populations.

de Andrade M, Li Y, Marks RS, et al.
Genetic variants associated with the risk of chronic obstructive pulmonary disease with and without lung cancer.
Cancer Prev Res (Phila). 2012; 5(3):365-73 [PubMed] Free Access to Full Article Related Publications
Chronic obstructive pulmonary disease (COPD) is a strong risk factor for lung cancer. Published studies about variations of genes encoding glutathione metabolism, DNA repair, and inflammatory response pathways in susceptibility to COPD were inconclusive. We evaluated 470 single-nucleotide polymorphisms (SNP) from 56 genes of these three pathways in 620 cases and 893 controls to identify susceptibility markers for COPD risk, using existing resources. We assessed SNP- and gene-level effects adjusting for sex, age, and smoking status. Differential genetic effects on disease risk with and without lung cancer were also assessed; cumulative risk models were established. Twenty-one SNPs were found to be significantly associated with risk of COPD (P < 0.01); gene-based analyses confirmed two genes (GCLC and GSS) and identified three additional genes (GSTO2, ERCC1, and RRM1). Carrying 12 high-risk alleles may increase risk by 2.7-fold; eight SNPs altered COPD risk without lung cancer by 3.1-fold and 4 SNPs altered the risk with lung cancer by 2.3-fold. Our findings indicate that multiple genetic variations in the three selected pathways contribute to COPD risk through GCLC, GSS, GSTO2, ERCC1, and RRM1 genes. Functional studies are needed to elucidate the mechanisms of these genes in the development of COPD, lung cancer, or both.

Hsu LI, Chen WP, Yang TY, et al.
Genetic polymorphisms in glutathione S-transferase (GST) superfamily and risk of arsenic-induced urothelial carcinoma in residents of southwestern Taiwan.
J Biomed Sci. 2011; 18:51 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Arsenic exposure is an important public health issue worldwide. Dose-response relationship between arsenic exposure and risk of urothelial carcinoma (UC) is consistently observed. Inorganic arsenic is methylated to form the metabolites monomethylarsonic acid and dimethylarsinic acid while ingested. Variations in capacity of xenobiotic detoxification and arsenic methylation might explain individual variation in susceptibility to arsenic-induced cancers.
METHODS: To estimate individual susceptibility to arsenic-induced UC, 764 DNA specimens from our long-term follow-up cohort in Southwestern Taiwan were used and the genetic polymorphisms in GSTM1, GSTT1, GSTP1 and arsenic methylation enzymes including GSTO1 and GSTO2 were genotyped.
RESULTS: The GSTT1 null was marginally associated with increased urothelial carcinoma (UC) risk (HR, 1.91, 95% CI, 1.00-3.65), while the association was not observed for other GSTs. Among the subjects with cumulative arsenic exposure (CAE) ≥ 20 mg/L*year, the GSTT1 null genotype conferred a significantly increased cancer risk (RR, 3.25, 95% CI, 1.20-8.80). The gene-environment interaction between the GSTT1 and high arsenic exposure with respect to cancer risk was statistically significant (multiplicative model, p = 0.0151) and etiologic fraction was as high as 0.86 (95% CI, 0.51-1.22). The genetic effects of GSTO1/GSTO2 were largely confined to high arsenic level (CAE ≥ 20). Diplotype analysis showed that among subjects exposed to high levels of arsenic, the AGG/AGG variant of GSTO1 Ala140Asp, GSTO2 5'UTR (-183)A/G, and GSTO2 Asn142Asp was associated with an increased cancer risk (HRs, 4.91, 95% CI, 1.02-23.74) when compared to the all-wildtype reference, respectively.
CONCLUSIONS: The GSTs do not play a critical role in arsenic-induced urothelial carcinogenesis. The genetic effects of GSTT1 and GSTO1 on arsenic-induced urothelial carcinogenesis are largely confined to very high exposure level.

Masoudi M, Saadat I, Omidvari S, Saadat M
Association between N142D genetic polymorphism of GSTO2 and susceptibility to colorectal cancer.
Mol Biol Rep. 2011; 38(7):4309-13 [PubMed] Related Publications
Expression pattern analysis has been revealed that glutathione S-transferase omega 2 (GSTO2, a member of class omega) is ubiquitously expressed. Over expression of GSTO2 induced apoptosis. The gene encoding GSTO2 was localized to human chromosome 10q24.3, a region that may harbor gene(s) involved in the developing of colorectal cancer. To investigate the association between GSTO2 N142D genetic polymorphism and susceptibility to colorectal cancer the present study was done. We studied 63 (26 females, 37 males) colorectal cancer patients and 126 (52 females, 74 males) healthy individuals. The control subjects were frequency matched for age and gender with the colorectal cancer group. The genotypes were performed using RFLP-PCR method. The ND and DD genotypes were not associated with risk of colorectal cancer, in comparison with the NN genotype. Family history for cancer in the first degree of relatives significantly differed between cases and controls (P = 0.012). The profiles of GSTO2 genotypes and family history in control and cancerous groups were compared to each other. Subjects with NN genotype and positive family history significantly were at high risk to develop colorectal cancer in comparison with subjects with DD or ND genotypes and negative family history (P = 0.003). Present findings indicating that GSTO2 NN genotype increase the risk of colorectal cancer in persons with positive family history for cancer in the first degree relatives.

Chung CJ, Pu YS, Su CT, et al.
Gene polymorphisms of glutathione S-transferase omega 1 and 2, urinary arsenic methylation profile and urothelial carcinoma.
Sci Total Environ. 2011; 409(3):465-70 [PubMed] Related Publications
Genetic polymorphisms in arsenic-metabolizing enzymes may be involved in the biotransformation of inorganic arsenic and may increase the risk of developing urothelial carcinoma (UC). The present study evaluated the roles of glutathione S-transferase omega 1 (GSTO1) and GSTO2 polymorphisms in UC carcinogenesis. A hospital-based case-control study was conducted. Questionnaire information and biological specimens were collected from 149 UC cases and 251 healthy controls in a non-obvious inorganic arsenic exposure area in Taipei, Taiwan. The urinary arsenic profile was determined using high-performance liquid chromatography and hydride generator-atomic absorption spectrometry. Genotyping for GSTO1 Ala140Asp and GSTO2 Asn142Asp was conducted using polymerase chain reaction-restriction fragment length polymerase. GSTO1 Glu208Lys genotyping was performed using high-throughput matrix-assisted laser desorption and ionization time-of-flight mass spectrometry. A significant positive association was found between total arsenic, inorganic arsenic percentage and monomethylarsonic acid percentage and UC, while dimethylarsinic acid percentage was significantly inversely associated with UC. The minor allele frequency of GSTO1 Ala140Asp, GSTO1 Glu208Lys and GSTO2 Asn142Asp was 18%, 1% and 26%, respectively. A significantly higher MMA% was found in people who carried the wild type of GSTO1 140 Ala/Ala compared to those who carried the GSTO1 140 Ala/Asp and Asp/Asp genotype (p=0.02). The homogenous variant genotype of GSTO2 142 Asp/Asp was inversely associated with UC risk (OR=0.17; 95% CI, 0.03 - 0.88; p=0.03). Large-scale studies will be required to verify the association between the single nucleotide polymorphisms of arsenic-metabolism-related enzymes and UC risk.

Chariyalertsak S, Purisa W, Sangrajrang S
Role of glutathione S-transferase omega gene polymorphisms in breast-cancer risk.
Tumori. 2009 Nov-Dec; 95(6):739-43 [PubMed] Related Publications
BACKGROUND/AIMS: Genetically influenced variations in the levels of activity and/or expression of some members of the glutathione S-transferase (GST) family have been identified as risk factors for cancer. One, GST omega (GSTO), has been found in a very limited number of studies. The aim of the present study was to investigate the influence of GSTO1 and GSTO2 polymorphisms on breast cancer risk.
METHODS: DNA isolated from the blood of 101 patients with breast cancer and 151 healthy controls was investigated for GSTO1 and GSTO2 polymorphisms by polymerase chain reaction-restriction-fragment length polymorphism.
RESULTS: Univariate and multivariate analyses showed no association between GSTO1 and GSTO2 genotypes and the risk of breast cancer. A higher prevalence of wild-type GSTO1 (A140/A140) was significantly correlated with advanced-stage breast cancer (OR = 0.1, 95% CI, 0.01-0.77), but the presence of the genotype did not correlate with patient age at diagnosis, menopausal status, tumor size, lymph node metastasis, or estrogen-receptor status. No association was found between GSTO2 genotype and clinicopathological features.
CONCLUSIONS: The results of the study suggest that GSTO1 and GSTO2 variants are not associated with breast cancer risk, but that wild-type GSTO1 (A140/A140) is likely among cases at an advanced stage.

Andonova IE, Justenhoven C, Winter S, et al.
No evidence for glutathione S-transferases GSTA2, GSTM2, GSTO1, GSTO2, and GSTZ1 in breast cancer risk.
Breast Cancer Res Treat. 2010; 121(2):497-502 [PubMed] Related Publications
Breast cancer is a complex disease and in recent years a number of breast cancer susceptibility genes have been identified, but the role of low penetrance susceptibility genes has not been completely resolved. Glutathione S-transferases (GSTs) are phase II xenobiotic metabolizing enzymes involved in the detoxification of chemical carcinogens and environmental pollutants and play an important role in cell defense mechanisms against oxidative stress. They have been in the spot light for the investigation of a potential association with breast cancer risk but so far, sparse or even no data for a potential contribution of GSTA2, GSTM2, GSTO, and GSTZ to breast cancer risk are available. We genotyped GSTA2_448_C > G (rs2180314), GSTA2_742_A > C (rs6577), GSTM2_-832_T > C (rs638820), GSTO1_-1242_G > A (rs2164624), GSTO1_419_A > C (rs4925), GSTO2_-183_A > G (rs2297235), GSTO2_342_A > G (rs156697), GSTZ1_-4378_A > G (rs1046428), and GSTZ1_94_G > A (rs3177427) by MALDI-TOF MS in the German GENICA breast cancer case-control collection of 1021 cases and 1015 controls and performed breast cancer risk association in general and with respect to the stratifications: menopausal status, family history of breast or ovarian cancer, use of oral contraceptives, use of hormone therapy, body mass index, and smoking as well as histopathological tumor characteristics including hormone receptor status, grade, histology, and node status. We did not observe any breast cancer risk associations and conclude that it is unlikely that glutathione S-transferases GSTA2, GSTM2, GSTO1, GSTO2, and GSTZ1 participate in breast cancer susceptibility.

Chung CJ, Hsueh YM, Bai CH, et al.
Polymorphisms in arsenic metabolism genes, urinary arsenic methylation profile and cancer.
Cancer Causes Control. 2009; 20(9):1653-61 [PubMed] Related Publications
Arsenic-metabolism-related genes can regulate the arsenic methylation process and may influence susceptibility to cancer. We evaluated the roles of arsenic metabolism genes on urinary arsenic profiles of repeated measurement with 15-year follow-up (1988-2004) through general linear model (GLM) and assessed the effect of the changed extent of urinary arsenic profiles on cancer risk. Questionnaire information and blood samples and two urines (1988 and 2004) were collected from 208 subjects in an arseniasis hyperendemic area in Taiwan. Profiles for concentrations of urinary arsenic were determined using HPLC-HG-AAS. The relative proportion of each arsenic species was calculated by dividing the concentration of each arsenic species by the total arsenic concentration. Genotyping was done using the 5' nuclease allelic discrimination (Taqman) assay. The incidence of cancer was identified through linking to the National Cancer Registry Systems. The Cox proportional hazards model and survival curves were used in the analyses. After a 15-year follow-up, baseline monomethylarsonic acid percentage (MMA%) and change in MMA% exhibited a significant dose-response relationship with cancer risk. Individuals with a higher baseline MMA% and a lower change in MMA% had the earliest cancer incidence (statistically significant). Through GLM, significant gene effects of arsenic (+3 oxidation state)-methyltransferase (AS3MT) on MMA%, dimethylarsinic acid percentage (DMA%) and DMA/MMA, purine nucleoside phosphorylase (PNP) on DMA% and glutathione S-transferase omega 2 (GSTO2) on inorganic arsenics (InAs%) were found. Our results show that MMA% might be a potential predictor of cancer risk. The change in MMA% was linked to individual cancer susceptibility related to AS3MT rs3740393.

Pongstaporn W, Pakakasama S, Sanguansin S, et al.
Polymorphism of glutathione S-transferase Omega gene: association with risk of childhood acute lymphoblastic leukemia.
J Cancer Res Clin Oncol. 2009; 135(5):673-8 [PubMed] Related Publications
PURPOSE: To evaluate the association between glutathione S-transferase Omega (GSTO) genes polymorphism and the susceptibility of acute lymphoblast leukemia (ALL).
METHODS: The polymorphism of GSTO1 and GSTO2 genes were analyzed in 99 ALL patients compared with 100 healthy children by PCR-based restriction fragment length polymorphism (RFLP) analysis.
RESULTS: GSTO1*A140D polymorphism was significantly associated with susceptibility to ALL (OR = 2.24, 95% CI = 1.16-4.35, P = 0.009) whereas, GSTO2*N142D genotype was significantly interacted with high risk group of childhood ALL (OR = 5.52, 95% CI = 1.72-17.71, P = 0.004).
CONCLUSION: This study revealed gene polymorphism in glutathione S-transferase Omega class may be a risk factor to the development of acute childhood lymphoblastic leukemia.

Peng DF, Razvi M, Chen H, et al.
DNA hypermethylation regulates the expression of members of the Mu-class glutathione S-transferases and glutathione peroxidases in Barrett's adenocarcinoma.
Gut. 2009; 58(1):5-15 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: The accumulation of reactive oxygen species and subsequent oxidative DNA damage underlie the development of Barrett's oesophagus (BO) and its progression to Barrett's dysplasia (BD) and adenocarcinoma (BAC).
METHODS: The promoter regions of 23 genes of the glutathione S-transferase (GST) and glutathione peroxidase (GPX) families were systematically analysed. Quantitative bisulfite pyrosequencing, real-time RT-PCR, western blot and immunohistochemical (IHC) analysis methods were utilised in this study.
RESULTS: 14 genes were identified that have CpG islands around their transcription start sites: GSTs (GSTM2-M5, GSTA4, GSTP1, GSTZ1, GSTT2, GSTO1 and GSTO2) and GPXs (GPX1, GPX3, GPX4 and GPX7). Analysis of an initial set of 20 primary samples demonstrated promoter DNA hypermethylation and mRNA downregulation of GPX3, GPX7, GSTM2, GSTM3 and GSTM5 in more than half of the BAC samples. Further analysis of 159 primary human samples (37 normal, 11 BO, 11 BD and 100 BACs) indicated frequent hypermethylation (>or=10% methylation) of GPX3 (62%), GPX7 (67%), GSTM2 (69.1%) and GSTM3 (15%) in BACs. A significant inverse correlation between DNA methylation and mRNA expression level was shown for GPX3 (p<0.001), GPX7 (p = 0.002), GSTM2 (p<0.001) and GSTM5 (p = 0.01). Treatment of oesophageal cancer cell lines with 5-aza-2'-deoxycytidine and trichostatin-A led to reversal of the methylation pattern and re-expression of these genes at the mRNA and protein levels. The IHC analysis of GPX3, GPX7 and GSTM2 on a tissue microarray that contained 75 BACs with normal squamous oesophageal samples demonstrated an absent to weak staining in tumours (52% for GPX3, 57% for GPX7 and 45% for GSTM2) and a moderate to strong immunostaining in normal samples.
CONCLUSION: Epigenetic inactivation of members of the glutathione pathway can be an important mechanism in Barrett's tumourigenesis.

Masoudi M, Saadat I, Omidvari S, Saadat M
Genetic polymorphisms of GSTO2, GSTM1, and GSTT1 and risk of gastric cancer.
Mol Biol Rep. 2009; 36(4):781-4 [PubMed] Related Publications
OBJECTIVE: The glutathione S-transferases (GSTs) are a superfamily of proteins that participates in detoxification. The GSTs were dividing into several classes including omega (GSTO), micro (GSTM) and theta (GSTT) classes. In human GSTO2, GSTM1, and GSTT1 are polymorphic. In order to study whether GSTO2, GSTM1, and GSTT1 polymorphisms are associated with increased gastric cancer risk in Iranian patients, the present case-control study was done.
METHODS: Genomic DNA was extracted from peripheral blood of 67 gastric cancer patients and 134 control subjects. The genotyping was performed using PCR-based method. The possible association of gastric cancer with the GSTO2 N142D polymorphism was estimated with assuming additive, dominant, and recessive effect of the variant 142D allele. To investigate whether profiles of GST genotypes are associated with the risk of gastric cancer, we used unconditional logistic regression analysis.
RESULTS: The GSTO2 142D allele in additive, dominant and recessive models was not associated with the risk. Because GSTM1, GSTT1, and GSTO2 genes belong to low-penetrance genes which might be involved in the carcinogenesis, patients and controls without family of cancer in first-degree relatives were also analyzes separately. To investigate whether profiles of GST genotypes are associated with the risk of gastric cancer, we used unconditional logistic regression analysis with GSTM1, GSTT1, and GSTO2 genotypes as predictor factors. The GSTO2 DD genotype was associated with decreased risk as compared to GSTO2 NN genotype (OR = 0.21, 95% CI: 0.05-0.92, P = 0.038).
CONCLUSIONS: Present findings show that GSTO2 DD genotype decreases the risk of gastric cancer in individuals without history of cancer in their first-degree relatives.

White DL, Li D, Nurgalieva Z, El-Serag HB
Genetic variants of glutathione S-transferase as possible risk factors for hepatocellular carcinoma: a HuGE systematic review and meta-analysis.
Am J Epidemiol. 2008; 167(4):377-89 [PubMed] Related Publications
The authors performed a systematic review and meta-analysis to determine the effect of polymorphisms in genes encoding glutathione S-transferases (GSTs), phase II isoenzymes involved in cellular detoxification, on risk of hepatocellular carcinoma (HCC). Fifteen eligible studies were identified: 14 evaluated GSTM1; 13, GSTT1; three, GSTP1; and one each evaluated GSTM2, GSTM3, GSTA1, GSTA4, GSTO1, and GSTO2, respectively. All were case-control studies performed in populations with high (Asian, African) and medium (European) HCC incidence rates. Random-effects meta-analyses suggested a small excess risk of HCC with GSTT1 null (odds ratio (OR) = 1.19, 95% confidence interval (CI): 0.99, 1.44) and possibly GSTM1 null (OR = 1.16, 95% CI: 0.89, 1.53) genotypes. Cumulative meta-analyses demonstrated that both pooled estimators generally trended toward a small excess risk with publication of more recent studies. Results for GSTP1 A313G suggested no excess risk (OR = 0.75, 95% CI: 0.50, 1.15). A number of potentially interesting gene-gene and gene-environment interactions were reported, but these were too few and inconsistent to allow meta-analysis. The overall results suggest that there may be a small excess risk of HCC in individuals with GSTT1 null and possibly also with GSTM1 null genotypes. However, given the relatively limited total number of subjects examined and observed between-study heterogeneity, chance could not be excluded.

Leite JL, Morari EC, Granja F, et al.
Influence of the glutathione s-transferase gene polymorphisms on the susceptibility to basal cell skin carcinoma.
Rev Med Chil. 2007; 135(3):301-6 [PubMed] Related Publications
BACKGROUND: The identification of groups at high risk is fundamental to determine preventive strategies for skin cancer. Destructive reactive oxygen species produced by UVA or chemical carcinogens are metabolized by a series of enzymes. Polymorphisms of genes encoding for these enzymes may produce defective proteins with a diminished ability to detoxify a wide range of carcinogens.
AIMS: To ascertain the influence and potential interactions of several polymorphisms of genes encoding four important antioxidant GST enzymes in the susceptibility to cancer among Brazilians.
MATERIAL AND METHODS: We compared the genotypes of Glutathione S-Transferase mu, theta, pi and omega (GSTM1, GSTT1, GSTP1 and GSTO2) in a group of 102 patients with skin lesions and 124 controls.
RESULTS: Patients with Basal Cell Skin Carcinoma (BCC) presented the combined GSTM1-GSTT1+ genotype more frequently (49.1%) than controls (29.8%) (Fisher test; p=0.04), conferring a 2.273 (Odds Ratio; 95% CI=1.199-4.308) higher risk for BCC. We were not able to find any other association between genotypes or between any genotype and the patients' clinical features.
CONCLUSIONS: The GST profile may help identify Brazilian individuals at higher risk for BCC.

Morari EC, Lima AB, Bufalo NE, et al.
Role of glutathione-S-transferase and codon 72 of P53 genotypes in epithelial ovarian cancer patients.
J Cancer Res Clin Oncol. 2006; 132(8):521-8 [PubMed] Related Publications
PURPOSE: A series of polymorphisms in germ-line DNA have been investigated in an effort to delineate polygenic models of cancer susceptibility and prognosis. As low-penetrance susceptibility genes may combine additively or multiplicatively and contribute to cancer incidence and to the response to chemotherapy, we studied GSTT1, GSTM1, GSTO2, GSTP1 and codon 72 of p53 genotype profiles in ovarian cancer patients.
METHODS: We compared 69 ovarian cancer patients with 222 control healthy women paired for ethnic and life-style characteristics. Outcome was evaluated in 29 stage III and IV patients submitted to a platinum-based chemotherapy followed-up for 6-29 months (17 +/- 9 months).
RESULTS: GSTT1, GSTM1, GSTO2 and GSTP1 genes presented a similar genotype distribution, but codon 72 of p53 gene wild-type variant was less frequent in ovarian cancer patients than in controls (chi(2); P = 0.0004).
CONCLUSIONS: We were unable to demonstrate any association between the GST genotypes studied and the risk of ovarian cancer but the inheritance of a heterozygous Arg/Pro genotype of p53 increased the risk of ovarian cancer more than 2.5 times (OR = 2.571; 95% CI = 1.453-4.550). There was no association of the studied genes to any clinical or pathological feature of the patients or to their response to chemotherapy.

Pongstaporn W, Rochanawutanon M, Wilailak S, et al.
Genetic alterations in chromosome 10q24.3 and glutathione S-transferase omega 2 gene polymorphism in ovarian cancer.
J Exp Clin Cancer Res. 2006; 25(1):107-14 [PubMed] Related Publications
The molecular basis of ovarian cancer development has not been fully elucidated. In this study, genetic alterations in ovarian cancer were identified by arbitrarily primed polymerase chain reaction (AP-PCR). A gene in DNA fingerprinting, amplified from primer AE11, was cloned, sequenced, and identified by comparison with known genes in the genome database. Gene amplification in chromosome 10q24.3 was identified and measured by real-time PCR. Three out of 20 cases harbored this gene amplification. This amplified region was identified as IVS-4 of the glutathione-S-transferase Omega 2 (GSTO2) gene. Therefore, the mutations in all 6 exons of the GSTO2 gene were determined. The A to G transition at codon 142 in exon 4 (AAT to GAT, N142D) was observed. The frequency of GSTO2 gene polymorphism was analyzed in 20 ovarian cancers, compared with 41 normal individuals. The gene frequencies of D142 and N142 allele in ovarian cancer cases were 0.3 and 0.7, whereas in normal females, they were 0.2 and 0.8, respectively. The odds ratio of D142 allele in ovarian cancer was 1.73 (95% CI = 0.51-5.89), indicating that this GSTO2 gene polymorphism may be associated with the risk of ovarian cancer.

Marahatta SB, Punyarit P, Bhudisawasdi V, et al.
Polymorphism of glutathione S-transferase omega gene and risk of cancer.
Cancer Lett. 2006; 236(2):276-81 [PubMed] Related Publications
Polymorphic glutathione S-transferase (GST) genes causing variations in enzyme activity may influence individual susceptibility to cancer. Though polymorphisms have been reported in GSTO1 and GSTO2, their predisposition to cancer risk has not yet been explored. In this case control study, 28 cases of hepatocellular carcinoma, 30 cases of cholangiocarcinoma, 31 cases of colorectal cancer, 30 cases of breast cancer and 98 controls were compared for frequencies of GSTO1 and GSTO2 genotypes. The statistical analysis provided the support for the difference in genotypic distribution for GSTO1*A140D between hepatocellular carcinoma (OR 23.83, CI 95%: 5.07-127), cholangiocarcinoma (OR 8.5, CI 95%: 2.07-37.85), breast cancer (OR 3.71, CI 95%: 1.09-13.02) and control. With regards to GSTO2*N140D polymorphism, there was no difference in genotypic distribution between all the types of cancer and control. The study suggests that GSTO1*A140D polymorphism could play an important role as a risk factor for the development of hepatocellular carcinoma, cholangiocarcinoma and breast cancer.

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