| 1. |
- Benhamou, S, et al.
(författare)
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Meta- and pooled analyses of the effects of glutathione S-transferase M1 polymorphisms and smoking on lung cancer risk
- 2002
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Ingår i: Carcinogenesis. - : Oxford University Press (OUP). - 0143-3334 .- 1460-2180. ; 23:8, s. 1343-1350
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Tidskriftsartikel (refereegranskat)abstract
- Susceptibility to lung cancer may in part be attributable to inter-individual variability in metabolic activation or detoxification of tobacco carcinogens. The glutathione S-transferase M1 (GSTM1) genetic polymorphism has been extensively studied in this context; two recent meta-analyses of case-control studies suggested an association between GSTM1 deletion and lung cancer. At least 15 studies have been published after these overviews. We undertook a new meta-analysis to summarize the results of 43 published case-control studies including >18 000 individuals. A slight excess of risk of lung cancer for individuals with the GSTM1 null genotype was found (odds ratio (OR) = 1.17, 95% confidence interval (CI) 1.07-1.27). No evidence of publication bias was found (P = 0.4), however, it is not easy to estimate the extent of such bias and we cannot rule out some degree of publication bias in our results. A pooled analysis of the original data of about 9500 subjects involved in 21 case-control studies from the International Collaborative Study on Genetic Susceptibility to Environmental Carcinogens (GSEC) data set was performed to assess the role of GSTM1 genotype as a modifier of the effect of smoking on lung cancer risk with adequate power. Analyses revealed no evidence of increased risk of lung cancer among carriers of the GSTM1 null genotype (age-, gender- and center-adjusted OR = 1.08, 95% CI 0.98-1.18) and no evidence of interaction between GSTM1 genotype and either smoking status or cumulative tobacco consumption.
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| 2. |
- Smits, KM, et al.
(författare)
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Association of metabolic gene polymorphisms with tobacco consumption in healthy controls
- 2004
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 110:2, s. 266-270
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Tidskriftsartikel (refereegranskat)abstract
- Polymorphisms in genes that encode for metabolic enzymes have been associated with variations in enzyme activity between individuals. Such variations could be associated with differences in individual exposure to carcinogens that are metabolized by these genes. In this study, we examine the association between polymorphisms in several metabolic genes and the consumption of tobacco in a large sample of healthy individuals. The database of the International Collaborative Study on Genetic Susceptibility to Environmental Carcinogens was used. All the individuals who were controls from the case-control studies included in the data set with information on smoking habits and on genetic polymorphisms were selected (n = 20,938). Sufficient information was available on the following genes that are involved in the metabolism of tobacco smoke constituents: CYPIAI, GSTMI, GSTTI, NAT2 and GSTPI. None of the tested genes was clearly associated with smoking behavior. Information on smoking dose, available for a subset of subjects, showed no effect of metabolic gene polymorphisms on the amount of smoking. No association between polymorphisms in the genes studied and tobacco consumption was observed; therefore, no effect of these genes on smoking behavior should be expected.
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| 3. |
- Pessah-Rasmussen, H, et al.
(författare)
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Glutathione transferase activity in human vessels and in cultured arterial smooth muscle cells
- 1993
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Ingår i: International Angiology. - 0392-9590. ; 12:4, s. 54-348
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Tidskriftsartikel (refereegranskat)abstract
- Glutathione transferases play an important role in the detoxification of many different endogeneous and exogenous compounds such as metabolites of polycyclic aromatic hydrocarbons (PAH) of cigarette tar. There is evidence that PAH may be atherogenic. The glutathione transferase activity towards trans-stilbene oxide (GST-tSBO) can be separated in blood in GST-positive and GST-negative phenotypes. We have previously suggested that the GST-negative phenotype may be associated with a higher morbidity in intermittent claudication among middle aged smokers. In the present study, GST-tSBO could easily be measured in human, rabbit and bovine arterial smooth muscle cells (SMC) in culture. The level of GST-tSBO was higher in rabbit than in bovine SMC. It was stable in bovine SMC during 5 cell passages and it could be induced twofold by long-time incubation with dimethylsulfoxide-soluble particulate matter from cigarette smoke or 3,4-benzo(a)pyrene. There was a positive correlation between the level of GST-tSBO in blood and in "healthy" arterial and venous tissue from individuals operated with coronary bypass. The enzyme levels in arterial tissue were lower than in venous tissue. GST-tSBO in atherosclerotic segments of human arteries was lower than in "healthy" segments from the same artery. These findings suggest that the arterial wall may have a low defense against toxic compounds that may decrease further as atherosclerosis proceeds. It is concluded that SMC are suitable for the study of the effects of PAH in relation to GST-tSBO and that the enzyme activity in blood will reflect the individual GST-tSBO phenotype also in vascular tissues.
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| 4. |
- Taioli, E, et al.
(författare)
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Polymorphisms in CYP1A1, GSTM1, GSTT1 and lung cancer below the age of 45 years
- 2003
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Ingår i: International Journal of Epidemiology. - : Oxford University Press (OUP). - 1464-3685 .- 0300-5771. ; 32:1, s. 60-63
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Tidskriftsartikel (refereegranskat)abstract
- Background A genetic component of early-onset lung cancer has been suggested. The role of metabolic gene polymorphisms has never been studied in young lung cancer cases. Phase 1 and Phase 2 gene polymorphisms are involved in tobacco carcinogens' metabolism and therefore in lung cancer risk. Methods The effect of metabolic gene polymorphisms on lung cancer at young ages was studied by pooling data from the Genetic Susceptibility to Environmental Carcinogens (GSEC) database. All primary lung cancer cases of both sexes who were Caucasian and less than or equal to45 years of age at diagnosis, and the corresponding controls were selected. We obtained 261 cases and 1452 controls. Results There was a marginally significant association between lung cancer and GST1 null genotype (OR = 1.2; 95% Cl: 1.0-1.6), and a significant association between lung cancer and the homozygous CYP1A1 Msp1 variant allele (CYP1A1*2A and *2B) genotype (OR = 4.7 95% Cl: 1.2-19.0). When data were stratified by smoking status, the association between CYP1A1 genotype and lung cancer was confined to never smokers. Conclusions These results suggest that metabolic genetic factors play a role in lung cancer developing at young ages.
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| 5. |
- Hertervig, Erik, et al.
(författare)
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The Expression of Glutathione Transferase μ in Patients with Inflammatory Bowel Disease
- 1994
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 29:8, s. 729-735
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Glutathione transferases (GST) are a group of multifunctional enzymes important in the detoxification of many electrophiles and, in addition, fatty acid hydroperoxides, thus limiting tissue damage from oxidative free radical attack. Of the four classes of GST (alpha, mu, pi, and theta), a class mu isoenzyme, GST mu, is dominantly inherited and is expressed in approximately half of the population. GST mu expression was examined in patients with inflammatory bowel disease and correlated to clinical course, extension, and age of onset of the diseases. METHODS: GST mu can be measured as GST activity against trans-stilbene oxide. This GST activity was measured in whole blood in 179 patients with ulcerative colitis, 109 patients with Crohn's disease, and 449 age-matched controls. RESULTS: Frequencies of GST mu expression were as follows: controls (n = 449, 51.2%), mild ulcerative colitis (n = 76, 47.3%), moderate ulcerative colitis (n = 43, 46.5%), and severe ulcerative colitis (characterized by colectomy) (n = 60, 36.7%). This trend was, however, not significant (p = 0.094). Patients with onset of the colitis before the age of 30 years (n = 91) had a lower frequency of GST mu expression (35.2%) than patients with a later onset (n = 88, 52.3%) (p < 0.05). This difference was more pronounced among the colectomized patients (19.4% versus 55.2%) (p < 0.01). In Crohn's disease, patients with colitis had a lower frequency of GST mu expression (n = 29, 31.0%) than controls; however, this was not statistically significant (p = 0.055). No difference was found with regard to age of onset. CONCLUSION: We conclude that in patients with ulcerative colitis, lack of GST mu is related to early age of onset and a more severe clinical course leading to colectomy.
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| 6. |
- Pessah-Rasmussen, H, et al.
(författare)
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Human fibroblasts lacking trans-stilbene oxide active glutathione transferase exhibit increased cell death when exposed to polycyclic aromatic hydrocarbons
- 1992
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Ingår i: Pharmacology and Toxicology. - : Wiley. - 0901-9928 .- 1600-0773. ; 70:5 Pt 1, s. 5-361
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Tidskriftsartikel (refereegranskat)abstract
- Glutathione transferases (GST) are detoxifying enzymes who act with many endogenous and exogenous substances such as polycyclic aromatic hydrocarbons (PAH). The GST activity towards trans-stilbene oxide (GST-tSBO) is inherited in an autosomal dominant fashion and can be separated in high (GST-positive) and low (GST-negative) phenotypes when measured in blood. Human fibroblast cultures were established from males matched for age, smoking habits and clinical manifestations of atherosclerosis. Matched pairs of GST-negative and GST-positive fibroblasts were studied. There was a very strong correlation between the levels of GST-tSBO in peripheral blood and in cultured fibroblasts within the same individual. When fibroblasts were exposed to benzo(a)pyrene (BP) or dimethylbenzanthracene (DMBA) GST-negative cells produced relatively more collagen than GST-positive cells. GST-negative fibroblasts showed a greater cell death than GST-positive fibroblasts as well among controls as after exposure to PAH. It is concluded that lack of GST-tSBO is easily discriminated in cultured skin fibroblasts. GST-negative and GST-positive fibroblasts showed different susceptibility towards some toxic stimuli that might be of importance in atherogenesis.
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