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Konstantinos P. Economopoulos - One of the best experts on this subject based on the ideXlab platform.
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glutathione s transferase m1 t1 and p1 polymorphisms and ovarian cancer risk a meta analysis
International Journal of Gynecological Cancer, 2010Co-Authors: Konstantinos P. Economopoulos, Theodoros N. Sergentanis, Nikos F VlahosAbstract:Introduction: Cytosolic glutathione S-transferase (GST) comprises multiple isoenzymes that catalyze reactions between glutathione and lipophilic compounds with electrophilic centers, resulting in the neutralization of toxic compounds, xenobiotics, and products of oxidative stress. Several studies have examined whether GST polymorphisms (GSTM1 null/present genotype, GSTT1 null/present genotype, and GSTP1 Ile105Val) represent risk factors for ovarian cancer, as they all may denote reduced enzyme activity. This meta-analysis aimed to examine the associations between the aforementioned polymorphisms and ovarian cancer risk. Methods: The MEDLINE database was searched up to September 2009 using the appropriate terms. Case-control studies with no mutually overlapping populations were selected. Pooled odds ratios (ORs) were appropriately derived from fixed-effects or random-effects models. Meta-regression with publication year was also performed. Results: Eight studies regarding GSTM1 null polymorphism status (2357 cases and 3044 controls), 6 studies concerning GSTT1 null polymorphism (1923 cases and 2759 controls), and 3 studies on GSTP1 Ile105Val were included in the meta-analysis. The GSTM1 null genotype was not associated with an increased risk for ovarian cancer (pooled OR, 1.031; 95% confidence interval, 0.867-1.226; random effects). The GSTT1 null genotype was not associated with an increased ovarian cancer risk (pooled OR, 0.934; 95% confidence interval, 0.804-1.086; random effects); similarly, no significant associations were demonstrated for GSTP1 Ile105Val. Conclusions: The examined GSTM1, GSTT1, and GSTP1 genotype polymorphisms do not seem to confer any additional risk for ovarian cancer. Given that the studies included in this meta-analysis involve mainly white populations, these results cannot be extrapolated on other populations, and additional data are needed for future race-specific analyses.
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gstm1 gstt1 GSTP1 gsta1 and colorectal cancer risk a comprehensive meta analysis
European Journal of Cancer, 2010Co-Authors: Konstantinos P. Economopoulos, Theodoros N. SergentanisAbstract:Glutathione S-transferases (GSTs) catalyse reactions between glutathione and lipophilic compounds with electrophilic centres, leading to neutralisation of toxic compounds, xenobiotics and products of oxidative stress. Controversy exists about whether GST polymorphisms (GSTM1 null/present genotype, GSTT1 null/present genotype, GSTP1 Ile105Val and GSTA1 *A/*B) represent risk factors for colorectal cancer. This meta-analysis aims to examine the associations between the above-mentioned polymorphisms and colorectal cancer risk. Forty-four studies were eligible for GSTM1 (11,998 colorectal cancer cases, 17,552 controls), 34 studies for GSTT1 (8596 cases, 13,589 controls), 19 studies for GSTP1 (5421 cases, 7671 controls) and four studies for GSTA1 polymorphism (1648 cases, 2039 controls). Pooled odds ratios (ORs) were appropriately derived from fixed-effects or random-effects models. Separate analyses were conducted on Caucasian and Chinese populations. Where appropriate, sensitivity analysis concerning the deviation of genotype frequencies in controls from the Hardy-Weinberg equilibrium was performed. GSTM1 null allele carriers exhibited increased colorectal cancer risk in Caucasian populations (pooled OR=1.150, 95% confidence interval (CI): 1.060-1.248, random effects); no significant association was detected for Chinese subjects (pooled OR=1.025, 95% CI: 0.903-1.163, fixed effects). Similarly, GSTT1 null allele carriers exhibited increased colorectal cancer risk in Caucasian populations (pooled OR=1.312, 95% CI: 1.119-1.538, random effects); the association in Chinese subjects was not significant (pooled OR=1.068, 95% CI: 0.788-1.449, random effects). Concerning GSTP1 Ile105Val no significant associations were demonstrated in either race. GSTA1 *A/*B polymorphism was not associated with colorectal cancer risk. GSTM1 and GSTT1 null genotypes confer additional risk for colorectal cancer in Caucasian populations.
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GSTT1 and GSTP1 polymorphisms and breast cancer risk: a meta-analysis
Breast Cancer Research and Treatment, 2009Co-Authors: Theodoros N. Sergentanis, Konstantinos P. EconomopoulosAbstract:Cytosolic glutathione -transferase comprises multiple isoenzymes; studies have principally examined mu-1 (GSTM1: null/present), theta-1 (GSTT1: null/present) and pi-1 (GSTP1 Ile105Val) gene polymorphisms concerning breast cancer risk. Regarding GSTT1 and GSTP1 polymorphisms, studies remain controversial and no recent meta-analysis has appeared. This meta-analysis aims to examine whether GSTT1 and GSTP1 polymorphisms are associated with breast cancer risk. Separate analyses were performed on Chinese and non-Chinese populations, in an attempt to investigate race-specific effects. Eligible articles were identified by a search of MEDLINE bibliographic database for the period up to August 2009. Regarding GSTT1 null/present genotype, 41 case–control studies were eligible (16,589 breast cancer cases and 19,995 controls); 30 case–control studies were eligible for GSTP1 Ile105Val (16,908 cases and 20,016 controls). Pooled odds ratios (ORs) were appropriately derived from fixed-effects or random-effects models. At the overall analysis, the null GSTT1 genotype was associated with elevated breast cancer risk (pooled OR = 1.114, 95% CI: 1.035–1.199, random effects). However, the association seemed confined to non-Chinese populations (33 studies, pooled OR = 1.128, 95% CI: 1.042–1.221, random effects), given that the association was not significant in the subset of Chinese studies (eight studies, pooled OR = 1.061, 95% CI: 0.875–1.286, random effects). Regarding GSTP1 Ile105Val, no statistically significant associations were detected in non-Chinese populations (25 studies). On the other hand, the GG genotype was associated with increased breast cancer risk in Chinese populations (five studies, pooled OR = 1.297, 95% CI: 1.023–1.645, fixed effects); accordingly, the recessive model yielded statistically significant results (pooled OR = 1.273, 95% CI: 1.006–1.610, fixed effects). In conclusion, polymorphisms of both GSTT1 and GSTP1 genes seem associated with elevated breast cancer risk in a race-specific manner. Given the small number of Chinese studies, the finding on GSTP1 Ile105Val merits further investigation.
Theodoros N. Sergentanis - One of the best experts on this subject based on the ideXlab platform.
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glutathione s transferase m1 t1 and p1 polymorphisms and ovarian cancer risk a meta analysis
International Journal of Gynecological Cancer, 2010Co-Authors: Konstantinos P. Economopoulos, Theodoros N. Sergentanis, Nikos F VlahosAbstract:Introduction: Cytosolic glutathione S-transferase (GST) comprises multiple isoenzymes that catalyze reactions between glutathione and lipophilic compounds with electrophilic centers, resulting in the neutralization of toxic compounds, xenobiotics, and products of oxidative stress. Several studies have examined whether GST polymorphisms (GSTM1 null/present genotype, GSTT1 null/present genotype, and GSTP1 Ile105Val) represent risk factors for ovarian cancer, as they all may denote reduced enzyme activity. This meta-analysis aimed to examine the associations between the aforementioned polymorphisms and ovarian cancer risk. Methods: The MEDLINE database was searched up to September 2009 using the appropriate terms. Case-control studies with no mutually overlapping populations were selected. Pooled odds ratios (ORs) were appropriately derived from fixed-effects or random-effects models. Meta-regression with publication year was also performed. Results: Eight studies regarding GSTM1 null polymorphism status (2357 cases and 3044 controls), 6 studies concerning GSTT1 null polymorphism (1923 cases and 2759 controls), and 3 studies on GSTP1 Ile105Val were included in the meta-analysis. The GSTM1 null genotype was not associated with an increased risk for ovarian cancer (pooled OR, 1.031; 95% confidence interval, 0.867-1.226; random effects). The GSTT1 null genotype was not associated with an increased ovarian cancer risk (pooled OR, 0.934; 95% confidence interval, 0.804-1.086; random effects); similarly, no significant associations were demonstrated for GSTP1 Ile105Val. Conclusions: The examined GSTM1, GSTT1, and GSTP1 genotype polymorphisms do not seem to confer any additional risk for ovarian cancer. Given that the studies included in this meta-analysis involve mainly white populations, these results cannot be extrapolated on other populations, and additional data are needed for future race-specific analyses.
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gstm1 gstt1 GSTP1 gsta1 and colorectal cancer risk a comprehensive meta analysis
European Journal of Cancer, 2010Co-Authors: Konstantinos P. Economopoulos, Theodoros N. SergentanisAbstract:Glutathione S-transferases (GSTs) catalyse reactions between glutathione and lipophilic compounds with electrophilic centres, leading to neutralisation of toxic compounds, xenobiotics and products of oxidative stress. Controversy exists about whether GST polymorphisms (GSTM1 null/present genotype, GSTT1 null/present genotype, GSTP1 Ile105Val and GSTA1 *A/*B) represent risk factors for colorectal cancer. This meta-analysis aims to examine the associations between the above-mentioned polymorphisms and colorectal cancer risk. Forty-four studies were eligible for GSTM1 (11,998 colorectal cancer cases, 17,552 controls), 34 studies for GSTT1 (8596 cases, 13,589 controls), 19 studies for GSTP1 (5421 cases, 7671 controls) and four studies for GSTA1 polymorphism (1648 cases, 2039 controls). Pooled odds ratios (ORs) were appropriately derived from fixed-effects or random-effects models. Separate analyses were conducted on Caucasian and Chinese populations. Where appropriate, sensitivity analysis concerning the deviation of genotype frequencies in controls from the Hardy-Weinberg equilibrium was performed. GSTM1 null allele carriers exhibited increased colorectal cancer risk in Caucasian populations (pooled OR=1.150, 95% confidence interval (CI): 1.060-1.248, random effects); no significant association was detected for Chinese subjects (pooled OR=1.025, 95% CI: 0.903-1.163, fixed effects). Similarly, GSTT1 null allele carriers exhibited increased colorectal cancer risk in Caucasian populations (pooled OR=1.312, 95% CI: 1.119-1.538, random effects); the association in Chinese subjects was not significant (pooled OR=1.068, 95% CI: 0.788-1.449, random effects). Concerning GSTP1 Ile105Val no significant associations were demonstrated in either race. GSTA1 *A/*B polymorphism was not associated with colorectal cancer risk. GSTM1 and GSTT1 null genotypes confer additional risk for colorectal cancer in Caucasian populations.
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GSTT1 and GSTP1 polymorphisms and breast cancer risk: a meta-analysis
Breast Cancer Research and Treatment, 2009Co-Authors: Theodoros N. Sergentanis, Konstantinos P. EconomopoulosAbstract:Cytosolic glutathione -transferase comprises multiple isoenzymes; studies have principally examined mu-1 (GSTM1: null/present), theta-1 (GSTT1: null/present) and pi-1 (GSTP1 Ile105Val) gene polymorphisms concerning breast cancer risk. Regarding GSTT1 and GSTP1 polymorphisms, studies remain controversial and no recent meta-analysis has appeared. This meta-analysis aims to examine whether GSTT1 and GSTP1 polymorphisms are associated with breast cancer risk. Separate analyses were performed on Chinese and non-Chinese populations, in an attempt to investigate race-specific effects. Eligible articles were identified by a search of MEDLINE bibliographic database for the period up to August 2009. Regarding GSTT1 null/present genotype, 41 case–control studies were eligible (16,589 breast cancer cases and 19,995 controls); 30 case–control studies were eligible for GSTP1 Ile105Val (16,908 cases and 20,016 controls). Pooled odds ratios (ORs) were appropriately derived from fixed-effects or random-effects models. At the overall analysis, the null GSTT1 genotype was associated with elevated breast cancer risk (pooled OR = 1.114, 95% CI: 1.035–1.199, random effects). However, the association seemed confined to non-Chinese populations (33 studies, pooled OR = 1.128, 95% CI: 1.042–1.221, random effects), given that the association was not significant in the subset of Chinese studies (eight studies, pooled OR = 1.061, 95% CI: 0.875–1.286, random effects). Regarding GSTP1 Ile105Val, no statistically significant associations were detected in non-Chinese populations (25 studies). On the other hand, the GG genotype was associated with increased breast cancer risk in Chinese populations (five studies, pooled OR = 1.297, 95% CI: 1.023–1.645, fixed effects); accordingly, the recessive model yielded statistically significant results (pooled OR = 1.273, 95% CI: 1.006–1.610, fixed effects). In conclusion, polymorphisms of both GSTT1 and GSTP1 genes seem associated with elevated breast cancer risk in a race-specific manner. Given the small number of Chinese studies, the finding on GSTP1 Ile105Val merits further investigation.
Aavovaldur Mikelsaar - One of the best experts on this subject based on the ideXlab platform.
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polymorphic glutathione s transferase m1 is a risk factor of primary open angle glaucoma among estonians
Experimental Eye Research, 2000Co-Authors: Erkki Juronen, Gunnar Tasa, Siiri Veromann, Lii Parts, Anne Tiidla, Riina Pulges, Aleksei Panov, Leili Soovere, Kulle Koka, Aavovaldur MikelsaarAbstract:Abstract Primary open-angle glaucoma, the most common form of glaucoma is a slowly progressive atrophy of the optic nerve, characterized by loss of peripheral visual function and is usually associated with elevated intraocular pressure. The etiology and genetic risk factors of primary open-angle glaucoma are mostly unknown. The aim of this study was to find out whether the polymorphism at GSTM1, GSTM3, GSTT1 and GSTP1 loci is associated with increased susceptibility to glaucoma, because these polymorphic enzymes are susceptibility candidates for several diseases, including such eye disease as cataract. The phenotype of GSTM1 and GSTT1 was determined by ELISA and the genotype of GSTM3 and GSTP1 was detected by polymerase chain reaction. Four hundred and fifty two Estonians (250 glaucomas and 202 controls) participated in a case-control study. A significant association of the GSTM1 polymorphism with glaucoma was observed. The frequency of the GSTM1 positive individuals among the glaucoma group was significantly higher than in controls (60 vs 45.0%) with odds ratio of 1.83 (95% CI 1.26–2.66; P = 0.002). The risk among the GSTM1 positive individuals of developing glaucoma was even higher in the case of smoking: 62.7% of smokers were GSTM1 positive in the glaucoma group while only 33.3% of smokers had GSTM1 positive phenotype in controls (OR = 3.36; 95% CI 1.49–7.56; P = 0.012). An association with a lower level of significance was also found with the GSTM3 gene. Four% of the 250 patients with POAG were identified as carriers of the GSTM3 BB genotype, a proportion which was slightly higher than the 1.0% for the controls (OR = 4.17; 95% CI 0.90–19.24; P = 0.144). The frequencies of the GSTT1 and GSTP1 genotypes in both groups were not statistically different. The present study suggests that the GSTM1 polymorphism may be associated with increased risk of development of primary open-angle glaucoma.
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polymorphic glutathione s transferases as genetic risk factors for senile cortical cataract in estonians
Investigative Ophthalmology & Visual Science, 2000Co-Authors: Erkki Juronen, Gunnar Tasa, Siiri Veromann, Lii Parts, Anne Tiidla, Riina Pulges, Aleksei Panov, Leili Soovere, Kulle Koka, Aavovaldur MikelsaarAbstract:PURPOSE. To investigate the possible association between glutathione S-transferase GSTM1, GSTM3, GSTT1, and GSTP1 polymorphism and the occurrence of age-related cataracts in Estonian patients. METHODS. Patients with cortical (155), nuclear (77), posterior subcapsular (120), mixed type (151) of senile cataract and control individuals (202) were phenotyped for GSTM1 and GSTT1 by enzyme-linked immunosorbent assay and genotyped for GSTM3 and GSTP1 by polymerase chain reaction. RESULTS. The frequency of the GSTM1-positive phenotype was significantly higher in the cortical cataract group (60.6%) than in the controls (45.0%) with odds ratio of 1.88 (95% CI, 1.23-2.94; P = 0.004). The cortical cataract risk associated with the GSTM1-positive phenotype was increased in carriers of the combined GSTM1-positive/GSTT1-positive phenotype (OR = 1.99; 95% CI, 1.30-3.11; P = 0.002) and the GSTM1-positive/GSTM3 AA genotype (OR = 2.28; 95% CI, 1.51-3.73; P < 0.001). The highest risk of cortical cataract was observed in patients having all three susceptible genotypes (OR = 2.56; 95% CI, 1.59-4.11; P < 0.001). Also, a significant interaction between the presence of the GSTP1 * A allele and cortical cataract was found with prevalence of the GSTP1 * A allele among the cortical cataract cases compared with the controls. Ninety-five percent of subjects with cortical cataract had the GSTP1 (AA, AB, or AC) genotype, whereas in controls 87% of persons had a genotype with GSTP1 * A allele (OR = 3.1; 95% CI, 1.31-7.35; P = 0.007). In contrast to the GSTPI * A allele, the presence of the GSTPI * B allele in one or two copies leads to decreased cortical cataract risk (OR = 0.09 for GSTP1 BB genotype). CONCLUSIONS. The GSTM1-positive phenotype as well as the presence of the GSTP1 * A allele may be a genetic risk factor for development of cortical cataract.
Nikos F Vlahos - One of the best experts on this subject based on the ideXlab platform.
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glutathione s transferase m1 t1 and p1 polymorphisms and ovarian cancer risk a meta analysis
International Journal of Gynecological Cancer, 2010Co-Authors: Konstantinos P. Economopoulos, Theodoros N. Sergentanis, Nikos F VlahosAbstract:Introduction: Cytosolic glutathione S-transferase (GST) comprises multiple isoenzymes that catalyze reactions between glutathione and lipophilic compounds with electrophilic centers, resulting in the neutralization of toxic compounds, xenobiotics, and products of oxidative stress. Several studies have examined whether GST polymorphisms (GSTM1 null/present genotype, GSTT1 null/present genotype, and GSTP1 Ile105Val) represent risk factors for ovarian cancer, as they all may denote reduced enzyme activity. This meta-analysis aimed to examine the associations between the aforementioned polymorphisms and ovarian cancer risk. Methods: The MEDLINE database was searched up to September 2009 using the appropriate terms. Case-control studies with no mutually overlapping populations were selected. Pooled odds ratios (ORs) were appropriately derived from fixed-effects or random-effects models. Meta-regression with publication year was also performed. Results: Eight studies regarding GSTM1 null polymorphism status (2357 cases and 3044 controls), 6 studies concerning GSTT1 null polymorphism (1923 cases and 2759 controls), and 3 studies on GSTP1 Ile105Val were included in the meta-analysis. The GSTM1 null genotype was not associated with an increased risk for ovarian cancer (pooled OR, 1.031; 95% confidence interval, 0.867-1.226; random effects). The GSTT1 null genotype was not associated with an increased ovarian cancer risk (pooled OR, 0.934; 95% confidence interval, 0.804-1.086; random effects); similarly, no significant associations were demonstrated for GSTP1 Ile105Val. Conclusions: The examined GSTM1, GSTT1, and GSTP1 genotype polymorphisms do not seem to confer any additional risk for ovarian cancer. Given that the studies included in this meta-analysis involve mainly white populations, these results cannot be extrapolated on other populations, and additional data are needed for future race-specific analyses.
Lülüfer Tamer - One of the best experts on this subject based on the ideXlab platform.
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The glutathione-S-transferase gene polymorphisms (Gstt1, Gstm1, and GSTP1) in patients with non-allergic nasal polyposis
European Archives of Oto-Rhino-Laryngology, 2009Co-Authors: Cengiz Özcan, Nurcan Aras Ateş, Lülüfer Tamer, Kemal GörürAbstract:There is an ongoing dilemma about the pathogenesis of nasal polyp (NP). The etiology of NP is multifactorial. Reactive oxygen species and oxidative stress are also suggested to be among the possible factors in NP development. Glutathione- S -transferase (GST) is one of the important detoxifying enzymes. It is not known whether GST plays any role in NP development. We aimed to investigate the relationship between GST subgroup (GSTT1, GSTM1, and GSTP1) polymorphisms, and NP development. Seventy-five patients with NP with or without asthma (NP with asthma: 22, NP without asthma: 53) were used as a study group. As much as 167 healthy individuals were involved as the control group. NP diagnosis was made by nasal endoscopy and paranasal sinus computed tomography (CT). NP was defined as the presence of endoscopically visible bilateral polyps originated from the middle meatus to the nasal cavity and affecting more than one paranasal sinus confirmed by CT. Blood was collected in EDTA-containing tubes and DNA was extracted from the leukocytes. The genotyping of polymorphisms of GSTT1, GSTM1, and GSTP1 were done using real time polymerase chain reaction. Chi-square (χ^2) and Fisher’s ( F ) exact tests were used for statistical evaluation. A 2-fold increased risk of NP could be found in individuals with the GSTT1 null genotype (OR = 2.03, 95% CI = 1.03–4.011). The distribution of GSTM1 null genotypes was not significantly different between the NP patients and controls and there was also no significance between the GSTP1 genotypes and NP. In conclusion, GST gene polymorphisms may be important in pathogenesis of NP. Additional studies which include larger study groups in different geographic localizations may be more useful to evaluate association with GST polymorphism and NP.
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glutathione s transferase m1 t1 and p1 genetic polymorphisms cigarette smoking and gastric cancer risk
Cell Biochemistry and Function, 2005Co-Authors: Lülüfer Tamer, Nurcan Aras Ateş, Bahadır Ercan, Cengiz Ateş, Tufan Elipek, Handan Çamdeviren, Hatice Yildirim, Ugur Atik, Suha AydinAbstract:Glutathione S-transferases (GSTs) belong to a superfamily of detoxification enzymes that provide critical defences against a large variety of chemical carcinogens and environmental toxicants. GSTs are present in most epithelial tissues of the human gastrointestinal tract. We investigated associations between genetic variability in specific GST genes (GSTM1, GSTT1 and GSTP1), the interaction with cigarette smoking and susceptibility to gastric cancer. The GSTM1, GSTT1 and GSTP1 polymorphisms were determined using real-time polymerase chain reaction (PCR) and fluorescence resonance energy transfer with Light Cycler Instrument. The study included 70 patients with gastric cancer and 204 controls. Associations between specific genotypes and the development of gastric cancer were examined by use of logistic regression to calculate odds ratios (OR) and 95% confidence intervals (CI). The GSTM1 homozygous null genotype was associated with an increased risk of developing gastric cancer (OR = 1.73; 95% CI = 1.10–3.04). GSTT1 homozygous null genotype and GSTP1 genotypes were not associated with the risk of gastric cancer. Also there was no difference between cases and controls in the frequency of val-105 and ile-105 alleles (p = 0.07). After grouping according to smoking status, GSTM1 null genotype was associated with an increased gastric cancer risk for smokers (OR = 2.15; 95% CI, 1.02–4.52). There were no significant differences in the distributions of any of the other GST gene combinations. Our findings suggest that the GSTM1 null genotype may be associated with an increased susceptibility to gastric cancer. Copyright © 2004 John Wiley & Sons, Ltd.
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Glutathione S-Transferase M1, T1, P1 Genotypes and Risk for Development of Colorectal Cancer
Biochemical Genetics, 2005Co-Authors: Nurcan Aras Ateş, Bahadır Ercan, Lülüfer Tamer, Cengiz Ateş, Tufan Elipek, Koray Öcal, Handan ÇamdevirenAbstract:The glutathione S-transferase (GST) supergene family is an important part of cellular enzyme defense against endogenous and exogenous chemicals, many of which have carcinogenic potential. The present investigation was conducted to detect a possible association between polymorphisms at the GSTM1 , GSTT1, and GSTP1 genes and the interaction with cigarette smoking and colorectal cancer incidence. We examined 181 patients with colorectal cancer and 204 controls. DNA was extracted from whole blood, and the GSTM1, GSTT1, and GSTP1 polymorphisms were determined using a real-time polymerase chain reaction and fluorescence resonance energy transfer with a Light-Cycler instrument. Associations between specific genotypes and the development of colorectal cancer were examined by use of logistic regression analysis to calculate odds ratios (OR) and 95% confidence intervals (CI). The GSTM1 polymorphism was associated with an increased risk of developing colorectal cancer (OR = 1.62, 95% CI: 1.06–2.46). Also the risk of colorectal cancer associated with the GSTT1 null genotype was 1.64 (95% CI: 1.10–2.59). Statistically no differences were found between patients with colorectal cancer and control groups for the GSTP1 Ile/Ile, Ile/Val and Val/Val genotypes. In addition, the frequencies of the GSTM1 and GSTT1 deletion genotypes differed significantly between the cases and controls for current smokers; the GSTT1 null genotype especially is associated with a greater risk of colorectal cancer (OR = 2.44, 95% CI: 1.24–4.81). The GSTM1 and GSTT1 deletions were associated with an increased risk of developing a transverse or rectal tumor (OR = 1.86, 95% CI: 1.15–3.00; OR = 1.70, 95% CI: 1.02–2.84; respectively). The glutathione S-transferase polymorphisms were not associated with risk in patients stratified by age. The risk of colorectal cancer increased as putative high-risk genotypes increased for the combined genotypes of GSTM1 null, GSTT1 null, and either GSTP1 valine heterozygosity or GSTP1 valine homozygosity (OR = 2.69, 95% CI: 1.02–7.11). In conclusion, the results obtained in this study clearly suggest that those susceptibility factors related to different GST polymorphic enzymes are predisposing for colorectal cancer.
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may glutathione s transferase m1 positive genotype afford protection against primary open angle glaucoma
Graefes Archive for Clinical and Experimental Ophthalmology, 2005Co-Authors: Ozlem Yildirim, Nurcan Aras Ateş, Lülüfer Tamer, Ayca Yilmaz, Uĝur Atik, Handan ÇamdevirenAbstract:Purpose To find out whether the polymorphism at GSTM1, GSTT1 and GSTP1 loci is associated with increased susceptibility to glaucoma.
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glutathione s transferase gene polymorphisms gstt1 gstm1 GSTP1 as increased risk factors for asthma
Respirology, 2004Co-Authors: Lülüfer Tamer, Nurcan Aras Ateş, Bahadır Ercan, Mukadder Calikoglu, Hatice Yildirim, Emel Saritas, Ali Unlu, Ugur AtikAbstract:Objectives: Asthma is a complex multifactorial disease with an obvious genetic predisposition, immunological aberration, and involvement of noxious environmental factors. Polymorphisms of the glutathione-S-transferase (GST) genes are known risk factors for some environmentally-related diseases. In the present study, the hypothesis that polymorphisms in the GSTT1, GSTM1 and GSTP1 genes are associated with atopic and nonatopic asthma was examined. Methodology: The study population consisted of 103 unrelated healthy individuals and 101 patients with bronchial asthma (64 atopic, 37 nonatopic). Asthma was diagnosed according to the American Thoracic Society statement. Genotyping of polymorphisms in the GSTT1, GSTM1 and GSTP1 genes was performed using real time polymerase chain reaction with a Light Cycler instrument and hybridization probes in combination with the Light Cycler DNA master hybridization probes kit. Results: Patients with atopic asthma (34.4%) had a higher prevalence of the GSTT1 null genotype than the nonatopic asthma patients (13.5%; OR = 3.83; 95% CI, 1.24–11.78). Asthma patients (63.4%) had a higher prevalence of the GSTM1 null genotype than the control group (40.8%; OR = 2.34; 95% CI, 1.31–4.20). Subjects with the GSTP1 homozygous Val/Val genotype had a 3.55-fold increased risk of having atopic asthma compared to nonatopic asthma (OR = 3.55; 95% CI, 1.10–12.56). Conclusions: These results suggest that the GSTT1 and GSTM1 null genotypes and the GSTP1 Val/Val polymorphism may play important roles in asthma pathogenesis. It is possible that intermediate electrophilic metabolites, arising in the first phase of detoxification, are not metabolized by GST enzymes in asthmatic patients and are not excreted. These intermediate metabolites may damage cells and generate oxidative stress, and so contribute to the pathogenesis of asthma.
