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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
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
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
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.
Alfred I. Neugut - One of the best experts on this subject based on the ideXlab platform.
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interactions among gstm1 GSTT1 and gstp1 polymorphisms cruciferous vegetable intake and breast cancer risk
2007Co-Authors: Julie A Britton, Mary Beth Terry, Mia M Gaudet, Alfred I. Neugut, Susan E. Steck, Steven L TeitelbaumAbstract:Isothiocyanates are anticarcinogenic phytochemicals found in cruciferous vegetables that both induce and are substrates for the gluthatione S-transferases (GSTs). The GSTs are phase II metabolizing enzymes involved in metabolism of various bioactive compounds. Functional polymorphisms in GST genes have been identified and may interact with cruciferous vegetable intake to affect cancer risk. We examined this hypothesis using data from the Long Island Breast Cancer Study Project, a population-based case-control study conducted in Long Island, NY, from 1996 to 1997. Cruciferous vegetable intake in the previous year was assessed via modified Block food frequency questionnaire. DNA was extracted from blood samples (n = 1052 cases and n = 1098 controls) and genotyped for GSTM1 deletion, GSTT1 deletion and GSTP1 Ile105Val using multiplex polymerase chain reaction and Taqman assays. Unconditional logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CI). We found an 86% increase in the OR for breast cancer among carriers of the GSTM1 null, GSTT1 null and GSTP 105Ile/Ile genotypes (OR = 1.86, 95% CI = 1.12, 3.08) and a 36% decrease in the OR among carriers of GSTM1 present, GSTT1 null and GSTP1 105Ile/Val + Val/Val genotypes (OR = 0.64, 95% CI = 0.42, 0.97) compared with GSTM1 present, GSTT1 present and GSTP1 105Ile/Ile carriers. We found no joint effects among GST polymorphisms and cruciferous vegetable intake and breast cancer risk. In conclusion, we found associations between specific combinations of three GST gene polymorphisms and breast cancer risk but these did not modify the association between cruciferous vegetable intake and breast cancer. Additional studies are needed to confirm the associations observed.
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
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
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.
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
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
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
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.
Thomas L. Vaughan - 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 survival among lung cancer patients
2003Co-Authors: Carol Sweeney, David L. Eaton, Patricia L. Stapleton, Valle Nazarstewart, Thomas L. VaughanAbstract:Glutathione S-transferase (GST) enzymes detoxify therapeutic drugs and reactive oxidants, so GST polymorphisms may influence survival after diagnosis of cancer. We evaluated survival according to GST polymorphisms in a population-based series of lung cancer patients. The study subjects (n = 274) were men diagnosed with lung cancer from 1993 through 1996 who participated in a case control study and provided a blood sample for genotyping. The presence of the GSTM1 and GSTT1 genes were assayed by multiplex PCR. Genotype at the GSTP1 Ile(105)Val substitution was determined by PCR and oligonucleotide ligation assay. The study subjects were followed for vital status through 2000, and overall survival was evaluated in Kaplan-Meier survival functions and Cox proportional hazards models. Subjects with the GSTM1 null genotype had shorter survival; the proportion of GSTM1 null subjects surviving at 5 years was 0.20 [95% confidence interval (CI) 0.14-0.27], compared with 0.29 (95% CI 0.22-0.37) for GSTM1 present subjects. The relative risk of death associated with GSTM1 null genotype, adjusted for stage at diagnosis and histology, was 1.36, 95% CI 1.04-1.80. There was no association between GSTT1 or GSTP1 genotype and survival in the overall study population, nor in a subgroup of patients treated with chemotherapy (n = 130). For GSTM1, our results are consistent with a previous study, which also observed that the GSTM1-null genotype, which confers susceptibility to lung cancer, was associated with shorter survival. Future studies of lung cancer survival should take into account GSTM1 genotype as well as investigate underlying mechanisms.
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A population-based study of glutathione S-transferase M1, T1 and P1 genotypes and risk for lung cancer
2003Co-Authors: Valle Nazar-stewart, Thomas L. Vaughan, Patricia L. Stapleton, Jason Loo, Berta Nicol-blades, David L. EatonAbstract:Abstract A deletion polymorphism for glutathione S -transferase M1 (GSTM1) has been related to risk for lung cancer among smokers in some studies but not in others. We examined GSTM1, a GSTT1 deletion polymorphism and a common GSTP1 gene variant ( iso → val ), as risk factors for lung cancer in a population-based case-control study of men. Cases ( N =274) were males identified from 1993 to 1996 through the Fred Hutchinson Cancer Research Center Cancer Surveillance System registry for western Washington State. Male age-matched controls ( N =501) were selected by random-digit dialing. Subjects participated in a telephone interview and blood draw. GSTM1 and GSTT1 were genotyped with a multiplex PCR assay using beta-globin as a positive control, and GSTP1 single nucleotide variant determined with PCR-based oligonucleotide ligation assays. GSTM1 absence was associated with a modest elevation in risk among all cases (odds ratio=1.27, 95% CI 0.91–1.77) and among non-small cell cancers (adenocarcinoma OR=1.58, 95% CI 0.99–2.52; squamous cell OR=1.40, 95% CI 0.83–2.34). Risk associated with GSTM1 null was increased two to sixfold among heavy smokers. GSTT1 was not associated with lung cancer risk and GSTP1 val was non-significantly associated with a modest reduction in risk, particularly among heavy smokers. No specific combination of GST genotypes was particularly associated with risk. These results support previous reports that the GSTM1 null genotype is associated with a modest increase in risk for lung cancer, particularly among heavy smokers, suggest no role for GSTT1 and the need for further study of GSTP1.
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glutathione s transferase m1 t1 and p1 polymorphisms as risk factors for renal cell carcinoma a case control study
2000Co-Authors: Carol Sweeney, David L. Eaton, Diana C Farrow, Stephen M Schwartz, Harvey Checkoway, Thomas L. VaughanAbstract:Renal cell carcinoma (RCC) has known environmental risk factors, notably smoking, and enzymes that biotransform carcinogens have high levels of activity in the kidney. However, a possible role of polymorphisms in these enzymes in RCC etiology has received little study. We investigated glutathione S-transferase (GST) polymorphisms in a population-based case-control study of RCC. Subjects completed a structured interview, and DNA was isolated from pathological material or buccal cells for 130 cases, and from blood for 505 controls. Genotypes for GSTM1 and GSTT1 were determined by multiplex PCR, and for GSTP1 by oligonucleotide ligation assay. The frequency of GSTM1 null genotype was 50.0% in cases and 50.5% in controls, with an adjusted odds ratio (OR) of 1.0 [95% confidence interval (CI), 0.6-1.6]. For GSTP1, the frequencies of genotypes AA, AG, and GG representing the Ile104Val variant were: cases, 44.6%, 43.1%, and 12.3%; controls, 43.4%, 44.0%, and 12.6%; OR for AG and GG, 1.0 (95% CI, 0.6-1.6). An excess of the GSTT1 null genotype was observed in cases compared with controls, 28.6% versus 18.5% (OR, 1.9; 95% CI, 1.1-3.4). The association with GSTT1 was present among both smokers and nonsmokers, but was modified by body mass index, a recognized risk factor for RCC; among subjects in the lowest tertile of body mass index, the OR for GSTT1 null was 4.8 (95% CI, 1.8-13.0). The association between GSTT1 null and increased RCC risk in this population-based study suggests that activity of the GSTT1 enzyme protects against RCC. This contrasts with a recent report of reduced risk of RCC associated with GSTT1 null in a cohort of trichloroethene-exposed workers and suggests that specific chemical exposures alter the effect of GSTT1 on cancer risk.
