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Dejan Dragicevic - One of the best experts on this subject based on the ideXlab platform.
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GSTO1*CC Genotype (rs4925) Predicts Shorter Survival in Clear Cell Renal Cell Carcinoma Male Patients.
Cancers, 2019Co-Authors: Tanja Radic, Vesna Coric, Marija Pljesa-ercegovac, Dejan Dragicevic, Marija Matic, Tatjana Djukic, Zoran Bukumiric, Nataša Avramović, Smiljana Mihailovic, Zoran DzamicAbstract:Omega class glutathione transferases, GSTO1-1 and GSTO2-2, exhibit different activities involved in regulation of inflammation, apoptosis and redox homeostasis. We investigated the the prognostic significance of GSTO1 (rs4925) and GSTO2 (rs156697 and rs2297235) polymorphisms in clear cell renal cell carcinoma (ccRCC) patients. GSTO1-1 and GSTO2-2 expression and phosphorylation status of phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/ /mammalian target of rapamycin (mTOR) and Raf/MEK/extracellular signal-regulated kinase (ERK) signaling pathways in non-tumor and tumor ccRCC tissue, as well as possible association of GSTO1-1 with signaling molecules were also assessed. GSTO genotyping was performed by quantitative PCR in 228 ccRCC patients, while expression and immunoprecipitation were analyzed by Western blot in 30 tissue specimens. Shorter survival in male carriers of GSTO1*C/C wild-type genotype compared to the carriers of at least one variant allele was demonstrated (p = 0.049). GSTO1*C/C genotype independently predicted higher risk of overall mortality among male ccRCC patients (p = 0.037). Increased expression of GSTO1-1 and GSTO2-2 was demonstrated in tumor compared to corresponding non-tumor tissue (p = 0.002, p = 0.007, respectively), while GSTO1 expression was correlated with interleukin-1β (IL-1β)/pro-interleukin-1β (pro-IL-1β) ratio (r = 0.260, p = 0.350). Interaction of GSTO1 with downstream effectors of investigated pathways was shown in ccRCC tumor tissue. This study demonstrated significant prognostic role of GSTO1 polymorphism in ccRCC. Up-regulated GSTO1-1 and GSTO2-2 in tumor tissue might contribute to aberrant ccRCC redox homeostasis.
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GSTO1 cc genotype rs4925 predicts shorter survival in clear cell renal cell carcinoma male patients
Cancers, 2019Co-Authors: Tanja Radic, Dejan Dragicevic, Marija Matic, Zoran Dzamic, Tatjana Djukic, Zoran Bukumiric, Smiljana Mihailovic, Marija Pljesaercegovac, Natasa Avramovic, Tatjana SimicAbstract:Omega class glutathione transferases, GSTO1-1 and GSTO2-2, exhibit different activities involved in regulation of inflammation, apoptosis and redox homeostasis. We investigated the the prognostic significance of GSTO1 (rs4925) and GSTO2 (rs156697 and rs2297235) polymorphisms in clear cell renal cell carcinoma (ccRCC) patients. GSTO1-1 and GSTO2-2 expression and phosphorylation status of phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/ /mammalian target of rapamycin (mTOR) and Raf/MEK/extracellular signal-regulated kinase (ERK) signaling pathways in non-tumor and tumor ccRCC tissue, as well as possible association of GSTO1-1 with signaling molecules were also assessed. GSTO genotyping was performed by quantitative PCR in 228 ccRCC patients, while expression and immunoprecipitation were analyzed by Western blot in 30 tissue specimens. Shorter survival in male carriers of GSTO1*C/C wild-type genotype compared to the carriers of at least one variant allele was demonstrated (p = 0.049). GSTO1*C/C genotype independently predicted higher risk of overall mortality among male ccRCC patients (p = 0.037). Increased expression of GSTO1-1 and GSTO2-2 was demonstrated in tumor compared to corresponding non-tumor tissue (p = 0.002, p = 0.007, respectively), while GSTO1 expression was correlated with interleukin-1β (IL-1β)/pro-interleukin-1β (pro-IL-1β) ratio (r = 0.260, p = 0.350). Interaction of GSTO1 with downstream effectors of investigated pathways was shown in ccRCC tumor tissue. This study demonstrated significant prognostic role of GSTO1 polymorphism in ccRCC. Up-regulated GSTO1-1 and GSTO2-2 in tumor tissue might contribute to aberrant ccRCC redox homeostasis.
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Concomitance of Polymorphisms in Glutathione Transferase Omega Genes Is Associated with Risk of Clear Cell Renal Cell Carcinoma.
The Tohoku journal of experimental medicine, 2018Co-Authors: Tanja Radic, Vesna Coric, Marija Pljesa-ercegovac, Gordana Basta-jovanovic, Sanja Radojevic-skodric, Dejan Dragicevic, Marija Matic, Ljiljana Bogdanovic, Zoran Dzamic, Tatjana SimicAbstract: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.
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GSTO1*C/GSTO2*G haplotype is associated with risk of transitional cell carcinoma of urinary bladder
International Urology and Nephrology, 2015Co-Authors: Tatjana Djukic, Tanja Radic, Vesna Coric, Marija Pljesa-ercegovac, Marija Matic, Tatjana Simic, Sonja Suvakov, Tatjana Pekmezovic, Ivana Novakovic, Dejan DragicevicAbstract:Purpose To clarify the role of genetic polymorphisms of GSTO1 (rs4925) and GSTO2 (rs156697) in individual susceptibility to urinary bladder cancer. Methods Case–control study consisting of 187 patients with histologically confirmed transitional cell carcinoma (TCC) of urinary bladder and 140 age- and gender-matched cancer-free controls was carried out. Genotyping of GSTO1 and GSTO2 was performed by polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP). Results We found that carriers of mutant GSTO2 *G/G genotype were at increased risk of the development of TCC (OR 2.6, 95 % CI 1.2–5.8, p = 0.041), while GSTO1 rs4925 polymorphism was not significantly associated with TCC risk ( p = 0.450). According to smoking status, smokers with GSTO2 *G/G genotype had significantly higher risk of TCC of urinary bladder (OR 4.3, 95 % CI 1.6–11.2, p = 0.003) compared to wild-type carriers with no smoking history. We further analyzed the effects of GSTO1 / GSTO2 haplotypes on TCC risk, based on the linkage disequilibrium found for GSTO1 (rs4925) and GSTO2 (rs156697) ( D ′ = 0.309, p = 0.001). The study subjects with GSTO1 *C/ GSTO2 *G ( GSTO1 wild-type/ GSTO2 mutant) haplotype were at the highest risk of the development of transitional cell carcinoma of urinary bladder (OR 2.8, 95 % CI 1.5–5.2, p = 0.002). Conclusions Our results indicate that GSTO1 *C/ GSTO2 *G haplotype is associated with increased risk of TCC. The modifying effect of GSTO2 *G/G genotype on individual susceptibility to TCC is more pronounced, when associated with smoking.
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Association of glutathione transferase omega polymorphisms with risk and survival in transitional cell carcinoma of urinary bladder
Medicinski podmladak, 2015Co-Authors: Tatjana Djukic, Ana Savic-radojevic, Dejan DragicevicAbstract:Exposure to chemical carcinogens, especially smoking and occupational exposure, is an etiologic factor for transitional cell carcinoma (TCC) of the urinary bladder. Cytosolic glutathione transferases (GSTs) are a superfamily of enzymes that protect normal cells by catalyzing conjugation reactions of electrophilic compounds, including carcinogens, to glutathione. Several types of allelic variations have been identified within GSTO class, with GSTO1*A140D (NCBI SNP ID: rs4925, 419 C to A) and GSTO2*N142D (NCBI SNP ID: rs156697, 424 A to G) being the most common. Individuals with the GSTO2*G/G genotype carry a higher risk for TCC. Our results indicate that GSTO1*C/GSTO2*G haplotype is associated with increased TCC risk, which is more pronounced in carriers of variant GSTO2*G/G combined with smoking. Furthermore, GSTO1*A/A and GSTO2*G/G genotypes may have a prognostic/pharmacogenomic role in patients with muscle invasive TCC. Newly discovered deglutathionylase activity of GSTO1 suggests its potential important role in redox perturbations present in TCC, which might contribute to progression of TCC
Maria Fuciarelli - One of the best experts on this subject based on the ideXlab platform.
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GSTO1 e155del polymorphism associated with increased risk for late onset alzheimer s disease association hypothesis for an uncommon genetic variant
Neuroscience Letters, 2012Co-Authors: Sara Piacentini, Renato Polimanti, Rosanna Squitti, Stefania Mariani, Simone Migliore, Fabrizio Vernieri, Paolo Maria Rossini, Dario Manfellotto, Maria FuciarelliAbstract:Glutathione S-transferases are multifunctional enzymes involved in cellular detoxification. A genetic linkage was found between Alzheimer's Disease (AD) and the chromosome 10q, where the GSTO1 and GSTO2 genes are located, leading to the hypothesis that GST Omega class (GSTO) genes may be an AD risk factor. Since it is still controversial, we decided to explore GSTO polymorphisms in Italian cohorts. We analyzed 119 AD patients and 114 healthy controls for the GSTO gene polymorphisms. In particular we investigated two common polymorphisms (GSTO1*A140D, GSTO2*N142D) and two uncommon variants (GSTO1*E155del, GSTO1*E208K) to find loci associated with AD risk. Detection of GSTO1*A140D and GSTO2*N142D was performed by PCR-RFLP, while GSTO1*E155del and GSTO1*E208K were detected using confronting two-pair primer and allele specific PCR, respectively. While GSTO1*A140D, GSTO1*E208K and GSTO2*N142D polymorphisms did not show significant outcomes, the GSTO1*E155del polymorphism is associated with AD [P=0.003; adjusted OR=3.70 (1.57-8.75)]. Our results suggest that GSTO1-1 plays a role in AD since the GSTO1*del155 variant is involved in changes in GSTO1-1 activities decreasing in enzyme stability. Specifically, three hypotheses may explain the role of GSTO1-1 in the pathophysiology of AD: the antioxidant activity of GSTO1-1 may protect brain tissue against oxidative stress; GSTO1-1 activity regulate interleukin-1β activation and its genetic variation may act to modulate inflammation in AD; GSTO1-1 is involved in the arsenic biotransformation pathway and gene polymorphisms may be implicated in the modulation of arsenic neurotoxicity. In conclusion, we hypothesized that GSTO1*E155del is an uncommon genetic variant associated with AD risk.
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GSTO1*E155del polymorphism associated with increased risk for late-onset Alzheimer's disease: Association hypothesis for an uncommon genetic variant
Neuroscience letters, 2011Co-Authors: Sara Piacentini, Renato Polimanti, Rosanna Squitti, Stefania Mariani, Simone Migliore, Fabrizio Vernieri, Paolo Maria Rossini, Dario Manfellotto, Maria FuciarelliAbstract:Glutathione S-transferases are multifunctional enzymes involved in cellular detoxification. A genetic linkage was found between Alzheimer's Disease (AD) and the chromosome 10q, where the GSTO1 and GSTO2 genes are located, leading to the hypothesis that GST Omega class (GSTO) genes may be an AD risk factor. Since it is still controversial, we decided to explore GSTO polymorphisms in Italian cohorts. We analyzed 119 AD patients and 114 healthy controls for the GSTO gene polymorphisms. In particular we investigated two common polymorphisms (GSTO1*A140D, GSTO2*N142D) and two uncommon variants (GSTO1*E155del, GSTO1*E208K) to find loci associated with AD risk. Detection of GSTO1*A140D and GSTO2*N142D was performed by PCR-RFLP, while GSTO1*E155del and GSTO1*E208K were detected using confronting two-pair primer and allele specific PCR, respectively. While GSTO1*A140D, GSTO1*E208K and GSTO2*N142D polymorphisms did not show significant outcomes, the GSTO1*E155del polymorphism is associated with AD [P=0.003; adjusted OR=3.70 (1.57-8.75)]. Our results suggest that GSTO1-1 plays a role in AD since the GSTO1*del155 variant is involved in changes in GSTO1-1 activities decreasing in enzyme stability. Specifically, three hypotheses may explain the role of GSTO1-1 in the pathophysiology of AD: the antioxidant activity of GSTO1-1 may protect brain tissue against oxidative stress; GSTO1-1 activity regulate interleukin-1β activation and its genetic variation may act to modulate inflammation in AD; GSTO1-1 is involved in the arsenic biotransformation pathway and gene polymorphisms may be implicated in the modulation of arsenic neurotoxicity. In conclusion, we hypothesized that GSTO1*E155del is an uncommon genetic variant associated with AD risk.
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Human GST Loci as Markers of Evolutionary Forces: GSTO1*E155del and GSTO1*E208K Polymorphisms May Be Under Natural Selection Induced by Environmental Arsenic
Disease markers, 2011Co-Authors: Renato Polimanti, Sara Piacentini, Flavio De Angelis, Gian Franco De Stefano, Maria FuciarelliAbstract:Over the last two decades, significant data has been accumulated linking Glutatione S-Transferases (GSTs) with the development of several diseases. Contemporary studies have demonstrated the impact of ethnicity on GST allele frequencies. The aim is to verify if the variability of GST genes reflects population demographic history or rather selective pressures. GST genes (GSTM1, GSTO1 GSTO2, GSTT1) were analysed in three Ecuadorian populations (Cayapas, n=114; Colorados, n=104; African-Ecuadorian, n=77) and compared with HapMap data. GST SNPs were determined using the PCR-RFLP method while GST null phenotype was determined using a Multiplex PCR. The population relationship achieved using GSTM1 positive/null, GSTO1*A140D, GSTO2*N142D and GSTT1 positive/null are in agreement with the data obtained using neutral polymorphisms: Amerindians are close to Asian populations and African-Ecuadorians to African populations. To what concerns GSTO1*del155 and GSTO1*K208 variants, allele frequencies never exceeded 10%, showing no significant differences in the Ecuadorian groups and in worldwide populations. The features of GSTO1*del155 and GSTO1*K208 variants and their association with arsenic biotransformation deficiency suggest the presence of a selection mechanism towards these loci. In particular, this hypothesis is strengthened by a possible linkage between these alleles and the susceptibility of arsenic-induced male infertility.
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human gst loci as markers of evolutionary forces GSTO1 e155del and GSTO1 e208k polymorphisms may be under natural selection induced by environmental arsenic
Disease Markers, 2011Co-Authors: Renato Polimanti, Sara Piacentini, Flavio De Angelis, Gian Franco De Stefano, Maria FuciarelliAbstract:Over the last two decades, significant data has been accumulated linking Glutatione S-Transferases (GSTs) with the development of several diseases. Contemporary studies have demonstrated the impact of ethnicity on GST allele frequencies. The aim is to verify if the variability of GST genes reflects population demographic history or rather selective pressures. GST genes (GSTM1, GSTO1 GSTO2, GSTT1) were analysed in three Ecuadorian populations (Cayapas, n=114; Colorados, n=104; African-Ecuadorian, n=77) and compared with HapMap data. GST SNPs were determined using the PCR-RFLP method while GST null phenotype was determined using a Multiplex PCR. The population relationship achieved using GSTM1 positive/null, GSTO1*A140D, GSTO2*N142D and GSTT1 positive/null are in agreement with the data obtained using neutral polymorphisms: Amerindians are close to Asian populations and African-Ecuadorians to African populations. To what concerns GSTO1*del155 and GSTO1*K208 variants, allele frequencies never exceeded 10%, showing no significant differences in the Ecuadorian groups and in worldwide populations. The features of GSTO1*del155 and GSTO1*K208 variants and their association with arsenic biotransformation deficiency suggest the presence of a selection mechanism towards these loci. In particular, this hypothesis is strengthened by a possible linkage between these alleles and the susceptibility of arsenic-induced male infertility.
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GSTA1, GSTO1 and GSTO2 gene polymorphisms in Italian asthma patients.
Clinical and experimental pharmacology & physiology, 2010Co-Authors: Renato Polimanti, Sara Piacentini, Dario Manfellotto, Barbara Moscatelli, Luisa Pellicciotti, Maria FuciarelliAbstract:Summary 1. Previous studies have established that genetic alterations in glutathione S-transferase enzymes may change the ability of the airway to deal with toxic substances and increase the risk of asthma. The present study analysed the association between asthma and GSTA1, GSTO1 and GSTO2 gene polymorphisms. 2. The GSTA1*-69C/T, GSTO1*A140D and GSTO2*N142D polymorphisms were detected by polymerase chain reaction–restriction fragment length polymorphism, whereas the GSTO1*E155del polymorphism was detected using the confronting two-pair primer method. 3. Distribution of the GSTA1*-69C/T genotype differed significantly between asthmatics and controls. Subjects with at least one allele -69T in the GSTA1 genotype have an increased risk of asthma (odds ratio (OR) 3.45; 95% confidence interval (CI) 1.80–6.62). The distribution of the GSTO1 genotype was nearly equal between the control group and asthmatics, however, the distribution of the GSTO2 gene differed significantly between asthmatics and controls (Chi-squared test). Subjects who had the GSTO2 homozygous D142 genotype were found to have an increased risk of asthma (OR 5.91; 95% CI 1.80–19.42). 4. The results show a potential association between the GST genes and asthma. This is particularly significant given that, in the literature, there are no epidemiological studies on alpha and omega classes of glutathione transferases in asthma.
Chien-jen Chen - One of the best experts on this subject based on the ideXlab platform.
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a significantly joint effect between arsenic and occupational exposures and risk genotypes diplotypes of cyp2e1 GSTO1 and gsto2 on risk of urothelial carcinoma
Toxicology and Applied Pharmacology, 2009Co-Authors: Yuan Hung Wang, Hung Yi Chiou, Chien-jen Chen, Kun Hung Shen, Cheng Huang Shen, Guang Dar Juang, Ling I. Hsu, Shauh Der YehAbstract:Cigarette smoking, arsenic and occupational exposures are well-known risk factors for the development of urothelial carcinoma (UC). Therefore, the aim of this study is to investigate whether the effect of cigarette smoking, alcohol consumption, arsenic and occupational exposures on risk of UC could be modified by genetic polymorphisms of cytochrome P450 2E1 and glutathione S-transferase omega. A hospital-based case-control study consisted of 520 histologically confirmed UC cases, and 520 age- and gender-matched cancer-free controls were carried out from September 1998 to December 2007. Genotyping of CYP2E1, GSTO1 and GSTO2 was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Subjects with both of cigarette smoking and alcohol consumption have a significantly increased UC risk (odds ratio [OR]=2.9; 95% confidence interval [CI]=1.9-4.4). Significantly increased UC risks of 1.5 and 1.9 were found for study subjects with high arsenic exposure and those who have been exposed to two or more occupational exposures, respectively. A significantly increased UC risk of 3.9 was observed in study subjects with H2-H2 diplotype of GSTO1 and GSTO2. The significantly highest UC risk of 9.0 was found for those with all environmental risk factors of cigarette smoking, alcohol consumption, arsenic and occupational exposures and two or more risk genotypes/diplotypes of CYP2E1, GSTO1 and GSTO2. Our findings suggest that a significantly joint effect of cigarette smoking, alcohol consumption, arsenic and occupational exposures and risk genotypes/diplotypes of CYP2E1, GSTO1 and GSTO2 on risk of UC was found.
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A significantly joint effect between arsenic and occupational exposures and risk genotypes/diplotypes of CYP2E1, GSTO1 and GSTO2 on risk of urothelial carcinoma.
Toxicology and applied pharmacology, 2009Co-Authors: Yuan Hung Wang, Hung Yi Chiou, Shauh Der Yeh, Kun Hung Shen, Cheng Huang Shen, Guang Dar Juang, Ling I. Hsu, Chien-jen ChenAbstract:Cigarette smoking, arsenic and occupational exposures are well-known risk factors for the development of urothelial carcinoma (UC). Therefore, the aim of this study is to investigate whether the effect of cigarette smoking, alcohol consumption, arsenic and occupational exposures on risk of UC could be modified by genetic polymorphisms of cytochrome P450 2E1 and glutathione S-transferase omega. A hospital-based case-control study consisted of 520 histologically confirmed UC cases, and 520 age- and gender-matched cancer-free controls were carried out from September 1998 to December 2007. Genotyping of CYP2E1, GSTO1 and GSTO2 was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Subjects with both of cigarette smoking and alcohol consumption have a significantly increased UC risk (odds ratio [OR]=2.9; 95% confidence interval [CI]=1.9-4.4). Significantly increased UC risks of 1.5 and 1.9 were found for study subjects with high arsenic exposure and those who have been exposed to two or more occupational exposures, respectively. A significantly increased UC risk of 3.9 was observed in study subjects with H2-H2 diplotype of GSTO1 and GSTO2. The significantly highest UC risk of 9.0 was found for those with all environmental risk factors of cigarette smoking, alcohol consumption, arsenic and occupational exposures and two or more risk genotypes/diplotypes of CYP2E1, GSTO1 and GSTO2. Our findings suggest that a significantly joint effect of cigarette smoking, alcohol consumption, arsenic and occupational exposures and risk genotypes/diplotypes of CYP2E1, GSTO1 and GSTO2 on risk of UC was found.
Songsak Petmitr - One of the best experts on this subject based on the ideXlab platform.
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Association of glutathione S-transferase omega gene polymorphisms with progression of head and neck cancer
Molecular biology reports, 2012Co-Authors: S. Sanguansin, Songsak Petmitr, P. O-charoenrat, W. PongstapornAbstract: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.
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Polymorphism of glutathione S-transferase Omega gene: association with risk of childhood acute lymphoblastic leukemia
Journal of Cancer Research and Clinical Oncology, 2009Co-Authors: W. Pongstaporn, S. Pakakasama, S. Sanguansin, S. Hongeng, Songsak PetmitrAbstract: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.
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Polymorphism of glutathione S-transferase omega gene and risk of cancer.
Cancer letters, 2005Co-Authors: Sujan Babu Marahatta, Phaibul Punyarit, Vajarabhongsa Bhudisawasdi, Anucha Paupairoj, Sopit Wongkham, Songsak PetmitrAbstract:Abstract 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.
Tatjana Djukic - One of the best experts on this subject based on the ideXlab platform.
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GSTO1*CC Genotype (rs4925) Predicts Shorter Survival in Clear Cell Renal Cell Carcinoma Male Patients.
Cancers, 2019Co-Authors: Tanja Radic, Vesna Coric, Marija Pljesa-ercegovac, Dejan Dragicevic, Marija Matic, Tatjana Djukic, Zoran Bukumiric, Nataša Avramović, Smiljana Mihailovic, Zoran DzamicAbstract:Omega class glutathione transferases, GSTO1-1 and GSTO2-2, exhibit different activities involved in regulation of inflammation, apoptosis and redox homeostasis. We investigated the the prognostic significance of GSTO1 (rs4925) and GSTO2 (rs156697 and rs2297235) polymorphisms in clear cell renal cell carcinoma (ccRCC) patients. GSTO1-1 and GSTO2-2 expression and phosphorylation status of phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/ /mammalian target of rapamycin (mTOR) and Raf/MEK/extracellular signal-regulated kinase (ERK) signaling pathways in non-tumor and tumor ccRCC tissue, as well as possible association of GSTO1-1 with signaling molecules were also assessed. GSTO genotyping was performed by quantitative PCR in 228 ccRCC patients, while expression and immunoprecipitation were analyzed by Western blot in 30 tissue specimens. Shorter survival in male carriers of GSTO1*C/C wild-type genotype compared to the carriers of at least one variant allele was demonstrated (p = 0.049). GSTO1*C/C genotype independently predicted higher risk of overall mortality among male ccRCC patients (p = 0.037). Increased expression of GSTO1-1 and GSTO2-2 was demonstrated in tumor compared to corresponding non-tumor tissue (p = 0.002, p = 0.007, respectively), while GSTO1 expression was correlated with interleukin-1β (IL-1β)/pro-interleukin-1β (pro-IL-1β) ratio (r = 0.260, p = 0.350). Interaction of GSTO1 with downstream effectors of investigated pathways was shown in ccRCC tumor tissue. This study demonstrated significant prognostic role of GSTO1 polymorphism in ccRCC. Up-regulated GSTO1-1 and GSTO2-2 in tumor tissue might contribute to aberrant ccRCC redox homeostasis.
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GSTO1 cc genotype rs4925 predicts shorter survival in clear cell renal cell carcinoma male patients
Cancers, 2019Co-Authors: Tanja Radic, Dejan Dragicevic, Marija Matic, Zoran Dzamic, Tatjana Djukic, Zoran Bukumiric, Smiljana Mihailovic, Marija Pljesaercegovac, Natasa Avramovic, Tatjana SimicAbstract:Omega class glutathione transferases, GSTO1-1 and GSTO2-2, exhibit different activities involved in regulation of inflammation, apoptosis and redox homeostasis. We investigated the the prognostic significance of GSTO1 (rs4925) and GSTO2 (rs156697 and rs2297235) polymorphisms in clear cell renal cell carcinoma (ccRCC) patients. GSTO1-1 and GSTO2-2 expression and phosphorylation status of phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/ /mammalian target of rapamycin (mTOR) and Raf/MEK/extracellular signal-regulated kinase (ERK) signaling pathways in non-tumor and tumor ccRCC tissue, as well as possible association of GSTO1-1 with signaling molecules were also assessed. GSTO genotyping was performed by quantitative PCR in 228 ccRCC patients, while expression and immunoprecipitation were analyzed by Western blot in 30 tissue specimens. Shorter survival in male carriers of GSTO1*C/C wild-type genotype compared to the carriers of at least one variant allele was demonstrated (p = 0.049). GSTO1*C/C genotype independently predicted higher risk of overall mortality among male ccRCC patients (p = 0.037). Increased expression of GSTO1-1 and GSTO2-2 was demonstrated in tumor compared to corresponding non-tumor tissue (p = 0.002, p = 0.007, respectively), while GSTO1 expression was correlated with interleukin-1β (IL-1β)/pro-interleukin-1β (pro-IL-1β) ratio (r = 0.260, p = 0.350). Interaction of GSTO1 with downstream effectors of investigated pathways was shown in ccRCC tumor tissue. This study demonstrated significant prognostic role of GSTO1 polymorphism in ccRCC. Up-regulated GSTO1-1 and GSTO2-2 in tumor tissue might contribute to aberrant ccRCC redox homeostasis.
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GSTO1*C/GSTO2*G haplotype is associated with risk of transitional cell carcinoma of urinary bladder
International Urology and Nephrology, 2015Co-Authors: Tatjana Djukic, Tanja Radic, Vesna Coric, Marija Pljesa-ercegovac, Marija Matic, Tatjana Simic, Sonja Suvakov, Tatjana Pekmezovic, Ivana Novakovic, Dejan DragicevicAbstract:Purpose To clarify the role of genetic polymorphisms of GSTO1 (rs4925) and GSTO2 (rs156697) in individual susceptibility to urinary bladder cancer. Methods Case–control study consisting of 187 patients with histologically confirmed transitional cell carcinoma (TCC) of urinary bladder and 140 age- and gender-matched cancer-free controls was carried out. Genotyping of GSTO1 and GSTO2 was performed by polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP). Results We found that carriers of mutant GSTO2 *G/G genotype were at increased risk of the development of TCC (OR 2.6, 95 % CI 1.2–5.8, p = 0.041), while GSTO1 rs4925 polymorphism was not significantly associated with TCC risk ( p = 0.450). According to smoking status, smokers with GSTO2 *G/G genotype had significantly higher risk of TCC of urinary bladder (OR 4.3, 95 % CI 1.6–11.2, p = 0.003) compared to wild-type carriers with no smoking history. We further analyzed the effects of GSTO1 / GSTO2 haplotypes on TCC risk, based on the linkage disequilibrium found for GSTO1 (rs4925) and GSTO2 (rs156697) ( D ′ = 0.309, p = 0.001). The study subjects with GSTO1 *C/ GSTO2 *G ( GSTO1 wild-type/ GSTO2 mutant) haplotype were at the highest risk of the development of transitional cell carcinoma of urinary bladder (OR 2.8, 95 % CI 1.5–5.2, p = 0.002). Conclusions Our results indicate that GSTO1 *C/ GSTO2 *G haplotype is associated with increased risk of TCC. The modifying effect of GSTO2 *G/G genotype on individual susceptibility to TCC is more pronounced, when associated with smoking.
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Association of glutathione transferase omega polymorphisms with risk and survival in transitional cell carcinoma of urinary bladder
Medicinski podmladak, 2015Co-Authors: Tatjana Djukic, Ana Savic-radojevic, Dejan DragicevicAbstract:Exposure to chemical carcinogens, especially smoking and occupational exposure, is an etiologic factor for transitional cell carcinoma (TCC) of the urinary bladder. Cytosolic glutathione transferases (GSTs) are a superfamily of enzymes that protect normal cells by catalyzing conjugation reactions of electrophilic compounds, including carcinogens, to glutathione. Several types of allelic variations have been identified within GSTO class, with GSTO1*A140D (NCBI SNP ID: rs4925, 419 C to A) and GSTO2*N142D (NCBI SNP ID: rs156697, 424 A to G) being the most common. Individuals with the GSTO2*G/G genotype carry a higher risk for TCC. Our results indicate that GSTO1*C/GSTO2*G haplotype is associated with increased TCC risk, which is more pronounced in carriers of variant GSTO2*G/G combined with smoking. Furthermore, GSTO1*A/A and GSTO2*G/G genotypes may have a prognostic/pharmacogenomic role in patients with muscle invasive TCC. Newly discovered deglutathionylase activity of GSTO1 suggests its potential important role in redox perturbations present in TCC, which might contribute to progression of TCC
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Glutathione S-transferase T1, O1 and O2 polymorphisms are associated with survival in muscle invasive bladder cancer patients.
PloS one, 2013Co-Authors: Tatjana Djukic, Tanja Radic, Vesna Coric, Marija Pljesa-ercegovac, Marija Matic, Sonja Suvakov, Tatjana Pekmezovic, Ana Savic-radojevic, Biljana Krivic, Dejan DragicevicAbstract: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.
