Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.5.1.18 (glutathione S-transferase)
22,582 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Multiple genes have been studied for potential associations with lung cancer. The gene most frequently associated with increased risk has been glutathione S-transferase M1 (GSTM1). The glutathione S-transferase enzyme family is known to catalyze detoxification of electrophilic compounds, including carcinogens, therapeutic drugs, environmental toxins, and products of oxidative stress. In this review, the authors summarize the available evidence associating lung cancer with the GSTM1 gene. They describe results from an updated meta-analysis of 98 published genetic association studies investigating the relation between the GSTM1 null variant and lung cancer risk including 19,638 lung cancer cases and 25,266 controls (counting cases and controls in each study only once). All studies considered, the GSTM1 null variant was associated with an increased risk of lung cancer (odds ratio (OR) = 1.22, 95% confidence interval (CI): 1.14, 1.30), but no increase in risk was seen (OR = 1.01, 95% CI: 0.91, 1.12) when only the five largest studies (>500 cases each) were considered. Furthermore, while GSTM1 null status conferred a significantly increased risk of lung cancer to East Asians (OR = 1.38, 95% CI: 1.24, 1.55), such a genotype did not confer increased risk to Caucasians. More data regarding the predictive value of GSTM1 genetic testing are needed before population-based testing may be reasonably considered.
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PMID:Glutathione S-transferase M1 (GSTM1) polymorphisms and lung cancer: a literature-based systematic HuGE review and meta-analysis. 1827 Mar 71

This study investigated associations between occupational pesticide exposure and renal cell carcinoma (RCC) risk. To follow-up on a previous report by Buzio et al., we also considered whether this association could be modified by glutathione S-transferase M1 and T1 (GSTM1 and GSTT1) genotypes. About 1097 RCC cases and 1476 controls from Central and Eastern Europe were interviewed to collect data on lifetime occupational histories. Occupational information for jobs held for at least 12 months duration was coded for pesticide exposures and assessed for frequency and intensity of exposure. GSTM1 and GSTT1 gene deletions were analyzed using TaqMan assays. A significant increase in RCC risk was observed among subjects ever exposed to pesticides [odds ratio (OR): 1.60; 95% confidence interval (CI): 1.00-2.55]. After stratification by genotypes, increased risk was observed among exposed subjects with at least one GSTM1 active allele (OR: 4.00; 95% CI: 1.55-10.33) but not among exposed subjects with two GSTM1 inactive alleles compared with unexposed subjects with two inactive alleles (P-interaction: 0.04). Risk was highest among exposed subjects with both GSTM1 and GSTT1 active genotypes (OR: 6.47; 95% CI: 1.82-23.00; P-interaction: 0.02) compared with unexposed subjects with at least one GSTM1 or T1 inactive genotype. In the largest RCC case-control study with genotype information conducted to date, we observed that risk associated with pesticide exposure was exclusive to individuals with active GSTM1/T1 genotypes. These findings further support the hypothesis that glutathione S-transferase polymorphisms can modify RCC risk associated with occupational pesticide exposure.
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PMID:Renal cell carcinoma, occupational pesticide exposure and modification by glutathione S-transferase polymorphisms. 1856 13

Genetic differences in the metabolism of xenobiotics have recently been suggested as modifiers of individual susceptibility to bladder cancer (BC). The objective of this study was to investigate the relationship between bladder tumor and variants of cytochrome p450 1A2 (CYP1A2) 734 C --> A, cytochrome p450 2D6 (CYP2D6) 1934 G --> A, glutathione S-transferase M1, (GSTM1 null), glutathione S-transferase T1 (GSTT1 null), and glutathione S-transferase P1 (GSTP1) I105 V. We investigated the distribution of these polymorphisms in 135 BC patients and in 128 age and sex-matched cancer-free controls. The polymorphisms were analyzed using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) assay and the multiplex PCR method. Genotype and allele frequencies and their associations with BC risk, demographic factors, smoking status, and tumor stage were investigated. The prevalence of GSTT1 null genotype in cases was 23%, compared with 7% in the control group (OR = 3.94, 95% CI = 1.70-9.38, P = 0.001). There was no association between the studied polymorphisms of CYP1A2, CYP2D6, GSTM1, and GSTP1 genes and BC. There was an association between smoking status and BC. These data seem to indicate that GSTT1 gene polymorphism may be associated with BC in the Turkish population studied. Further studies will be needed to clarify the role of such variation in determining susceptibility to BC.
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PMID:CYP1A2, CYP2D6, GSTM1, GSTP1, and GSTT1 gene polymorphisms in patients with bladder cancer in a Turkish population. 1869 May 46

Epidemiologic evidence suggests a possible association between genital use of talcum powder and risk of epithelial ovarian cancer; however, the biological basis for this association is not clear. We analyzed interactions between talc use and genes in detoxification pathways [glutathione S-transferase M1 (GSTM1), glutathione S-transferase T1 (GSTT1), and N-acetyltransferase 2 (NAT2)] to assess whether the talc/ovarian cancer association is modified by variants of genes potentially involved in the response to talc. Our analysis included 1,175 cases and 1,202 controls from a New England-based case-control study and 210 cases and 600 controls from the prospective Nurses' Health Study. We genotyped participants for the GSTM1 and GSTT1 gene deletions and three NAT2 polymorphisms. We used logistic regression to analyze the main effect of talc use, genotype, and gene-talc interactions in each population and pooled the estimates using a random-effects model. Regular talc use was associated with increased ovarian cancer risk in the combined study population (RR, 1.36; 95% CI, 1.14-1.63; P(trend) < 0.001). Independent of talc, the genes examined were not clearly associated with risk. However, the talc/ovarian cancer association varied by GSTT1 genotype and combined GSTM1/GSTT1 genotype. In the pooled analysis, the association with talc was stronger among women with the GSTT1-null genotype (P(interaction) = 0.03), particularly in combination with the GSTM1-present genotype (P(interaction) = 0.03). There was no clear evidence of an interaction with GSTM1 alone or NAT2. These results suggest that women with certain genetic variants may have a higher risk of ovarian cancer associated with genital talc use. Additional research is needed on these interactions and the underlying biological mechanisms.
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PMID:Talc use, variants of the GSTM1, GSTT1, and NAT2 genes, and risk of epithelial ovarian cancer. 1876 14

Human metabolism of benzene involves pathways coded for by polymorphic genes. To determine whether the genotype at these loci might influence susceptibility to the adverse effects of benzene exposure, 208 Bulgarian petrochemical workers and controls, whose exposure to benzene was determined by active personal sampling, were studied. The frequency of DNA single-strand breaks (DNA-SSB) was determined by alkaline elution, and genotype analysis was performed for five metabolic loci. Individuals carrying the NAD(P)H:quinone oxidoreductase 1 (NQO1) variant had significantly twofold increased DNA-SSB levels compared to wild-type individuals. The same result was observed for subjects with microsomal epoxide hydrolase (EPHX) genotypes that predict the fast catalytic phenotype. Deletion of the glutathione S-transferase T1 (GSTT1) gene also showed a consistent quantitative 35-40% rise in DNA-SSB levels. Neither glutathione S-transferase M1 (GSTM1) nor myeloperoxidase (MPO) genetic variants exerted any effect on DNA-SSB levels. Combinations of two genetic polymorphisms showed the same effects on DNA-SSB as expected from the data on single genotypes. The three locus genotype predicted to produce the highest level of toxicity, based on metabolic pathways, produced a significant 5.5-fold higher level of DNA-SSB than did the genotype predicted to yield the least genotoxicity.
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PMID:Genetic susceptibility to benzene toxicity in humans. 1883 23

Glutathione S-transferases (GSTs), superoxide dismutase 2 (SOD2) and NAD(P)H:quinone oxidoreductase 1 (NQO1) are anti-oxidant enzyme genes. Polymorphisms of GSTs, SOD2 and NQO1 have been reported to influence individual susceptibility to various diseases. In an earlier study, we obtained preliminary findings that a subset of glutathione S-transferase T1 (GSTT1)-wt patients with varicocele may exhibit good response to varicocelectomy. In this study, we extended the earlier study to determine the distribution of genotype of each gene in the infertile population and to evaluate whether polymorphism of these genes affects the results of surgical treatment of varicocele. We analyzed 72 infertile varicocele patients, 202 infertile patients without varicocele and 101 male controls. Genotypes of GSTs were determined by polymerase chain reaction (PCR). Genotyping of SOD2 and NQO1 was performed using the PCR-restriction fragment length polymorphism (PCR-RFLP) method. A significantly better response to varicocelectomy was found in patients with the GSTT1-wt genotype (63.2%) and NQO1-Ser/Ser genotype (80.0%) than in those with GSTT1-null genotype (35.3%) and NQO1-Pro/Pro or NQO1-Pro/Ser genotype (45.2%), respectively. The frequencies of glutathione S-transferase M1/T1, SOD2 and NQO1 genotypes did not differ significantly among the varicocele patients, idiopathic infertile patients and male controls. GSTT1 genotype is associated with improvement of semen parameters after varicocelectomy. As the number of patients with NQO1-Ser/Ser genotype was not sufficient to reach definite conclusions, the association of NQO1 genotype with varicocelectomy requires further investigation.
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PMID:Genetic polymorphisms in glutathione S-transferase T1 affect the surgical outcome of varicocelectomies in infertile patients. 1915 39

This study evaluated the influence of genetic polymorphism influencing drug metabolism on survival in taxane- and cisplatin-treated advanced gastric cancer (AGC). Peripheral blood samples from 207 AGC patients treated with first-line chemotherapy of taxane and cisplatin were used. We investigated polymorphisms that influenced the metabolism of taxane (ATP-binding cassette transporter B1 (ABCB1)), cisplatin (glutathione S-transferase M1 (GSTM1), glutathione S-transferase P1 (GSTP1), glutathione S-transferase T1 (GSTT1), excision repair cross complementing 1 (ERCC1), X-ray Cross Complementing group 3 (XRCC3), X-ray Cross Complementing group 4 (XRCC4), X-ray Cross Complementing group 1 (XRCC1), breast cancer (BRCA1)), and 5-fluorouracil (methylene tetrahydrofolate reductase (MTHFR), thymidylate synthase (TYMS)). A total of 207 patients were enrolled between May 2004 and Dec 2008, and 200 patients were analyzed. The overall response rate was 38.5%. Time to progression and overall survival time were 4.3 +/- 0.19 months and 11.9 +/- 1.05 months, respectively. There was no significant association between genetic polymorphism and response rate. However, the BRCA1 mutant TT homozygote was associated with significant prolongation of overall survival (hazard ratio [HR] = 0.43; 95% confidence interval [CI], 0.20-0.92; P = 0.03) and progression-free survival (HR = 0.51; 95% CI, 0.26-1.00; P = 0.05). Also, the XRCC1 194 CT genotype was associated with inferior overall survival, relative to the XRCC1 194 CC homozygotes (HR = 1.49; 95% CI, 0.11-2.07; P = 0.018).These findings suggest that BRCA1 TT and XRCC1 194 CT genotypes could be modest prognostic markers of AGC response in taxane- and cisplatin-treated patients.
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PMID:BRCA1 and XRCC1 polymorphisms associated with survival in advanced gastric cancer treated with taxane and cisplatin. 2033 23

Susceptibility to the respiratory effects of air pollution varies between individuals. Although some evidence suggests higher susceptibility for subjects carrying variants of antioxidant genes, findings from gene-pollution interaction studies conflict in terms of the presence and direction of interactions. The authors conducted a systematic review on antioxidant gene-pollution interactions which included 15 studies, with 12 supporting the presence of interactions. For the glutathione S-transferase M1 gene (GSTM1) (n=10 studies), only 1 study found interaction with the null genotype alone, although 5 observed interactions when GSTM1 was evaluated jointly with other genes (mainly NAD(P)H dehydrogenase [quinone] 1 (NQO1)). All studies on the glutathione S-transferase P1 (GSTP1) Ile105Val polymorphism (n=11) provided some evidence of interaction, but findings conflicted in terms of risk allele. Results were negative for glutathione S-transferase T1 (GSTT1) (n=3) and positive for heme oxygenase 1 (HMOX-1) (n=2). Meta-analysis could not be performed because there were insufficient data available for any specific gene-pollutant-outcome combination. Overall the evidence supports the presence of gene-pollution interactions, although which pollutant interacts with which gene is unclear. However, issues regarding multiple testing, selective reporting, and publication bias raise the possibility of false-positive findings. Larger studies with greater accuracy of pollution assessment and improved quality of conduct and reporting are required.
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PMID:Interactive effects of antioxidant genes and air pollution on respiratory function and airway disease: a HuGE review. 2134 47

The association between glutathione S-transferase M1 (GSTM1) and glutathione S-transferase T1 (GSTT1) null polymorphisms and oral cancer is not consistent across studies, and data on their interaction with smoking in oral cancer are lacking. The authors systematically searched PubMed and SciVerse Scopus for case-control studies examining the association between null genotypes of the GSTM1 and GSTT1 genes and oral cancer. Twenty-eight case-control studies published in English were identified. Summary odds ratios were derived via random-effects models. The summary odds ratio for the GSTM1 null genotype was 1.43 in Asians (95% confidence interval (CI): 1.14, 1.78; P < 0.01, I (2) = 73%) and 0.98 in Caucasians (95% CI: 0.76, 1.28; P = 0.91, I (2) = 0%). Case-only analysis of 6 studies (552 cases) showed an inverse multiplicative interaction between GSTM1 null polymorphisms and smoking (ever/high levels of smoking vs. never/low levels) (odds ratio (OR) = 0.51, 95% CI: 0.32, 0.82; P = 0.01, I (2) = 34%). The GSTT1 null genotype was not significantly associated with oral cancer in Asians (OR = 1.07, 95% CI: 0.82, 1.38; P = 0.63, I (2) = 65%) or Caucasians (OR = 1.04, 95% CI: 0.41, 2.65; P = 0.93, I (2) = 55%). In conclusion, the GSTM1 null genotype may be associated with a higher risk of oral cancer in Asians but not in Caucasians, and this effect may be modified by smoking status. The GSTT1 null genotype may not be associated with oral cancer.
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PMID:Glutathione S-transferase M1 (GSTM1) and glutathione S-transferase T1 (GSTT1) null polymorphisms, smoking, and their interaction in oral cancer: a HuGE review and meta-analysis. 2143 84

Genetic polymorphisms of enzymes involved in the metabolism of carcinogens are suggested to modify an individual's susceptibility to lung cancer. The purpose of this study was to investigate the relationship between lung cancer cases in Japan and variant alleles of cytochrome P450 (CYP) 2A6 (CYP2A6*4), CYP2A13 (CYP2A13*1-*10), CYP4B1 (CYP4B1*1-*7), sulfotransferase 1A1 (SULT1A1*2), glutathione S-transferase M1 (GSTM1 null), and glutathione S-transferase T1 (GSTT1 null). We investigated the distribution of these polymorphisms in 192 lung cancer patients and in 203 age- and sex-matched cancer-free controls. The polymorphisms were analyzed using various techniques including allele-specific PCR, hybridization probe assay, multiplex PCR, denaturing high-performance liquid chromatography (DHPLC), and direct sequencing. We also investigated allele and genotype frequencies and their association with lung cancer risk, demographic factors, and smoking status. The prevalence of the CYP2A6*4/*4 genotype in lung cancer cases was 3.6%, compared with 9.4% in the controls (adjusted OR = 0.36, 95% CI = 0.15-0.88, P = 0.025). In contrast, there was no association between the known CYP2A13, CYP4B1, SULT1A1, GSTM1, and GSTT1 polymorphisms and lung cancer. These data indicate that CYP2A6 deletions may be associated with lung cancer in the Japanese population studied.
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PMID:Association between cancer risk and drug-metabolizing enzyme gene (CYP2A6, CYP2A13, CYP4B1, SULT1A1, GSTM1, and GSTT1) polymorphisms in cases of lung cancer in Japan. 2179 72


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