Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242379 (lung cancer)
 71,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A close correlation between cigarette smoking associated lung cancer incidence and an Msp I restriction fragment length polymorphism (RFLP) of the human P-450 1A1 (CYP1A1) gene was found in a Japanese population in terms of genotype frequency and cigarette dose. A Val/Ile codon difference in the primary structure of the CYP1A1 protein (Val-, Ile-type) was in linkage disequilibrium with the Msp I RFLP. A synergistic increase in susceptibility to lung cancer was found when combining genotyping of CYP1A1 and the Mu-class of glutathione S-transferase (GST1). Interindividual variability in the genetic make-up of carcinogen metabolizing enzymes may thus be a key host factor to explain the differences in susceptibility to chemical carcinogenesis among individuals.
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PMID:The CYP1A1 gene and cancer susceptibility. 810 89

Paraffin-embedded tissue sections from 105 cases of human lung cancer were stained for four isozymes of GSTs by immunohistochemical PAP technique. Of the 16 cases of small cell lung cancer (SCLC) examined 14 were negative for all GST individuals, whereas one undifferentiated squamous cell type and one oat cell type treated with chemotherapy before operation were positive for GST-pi. The total positive rates of GST-pi, GSTs and GST-mu in 89 cases of non-SCLC were 75.3%, 13.5% and 9.7% separatively. Among them squamous cell carcinoma were stained positively for GST-pi in 93.5%, GSTs in 9.7% and GST-mu in 6.5%, while adenocarcinoma were in 69.7%, 15.2% and 6.1% respectively. The expression of GST-pi was weakened corresponding with the decreased degree of differentiation of cancer cell. GST-alpha was not detectable in all specimens studied. Ultrastructure location of GST-pi sites in 11 cases of non-SCLC was detected mainly on lysozymes and heterochromatin in cancer cell by transmission electronic microscopy utilizing colloidal gold labelled anti-GST-pi antibody. These results suggest that GST-pi may be an useful marker for differential diagnosis in histopathology and intrinsic sensitivity to anticancer drugs of lung cancer. GST-mu was expressed in some types of lung cancer with low positive rate and its usage as a marker needs further investigation.
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PMID:[Immunohistochemical investigation on the expression of glutathione S-transferases (GSTS) in lung cancer]. 824 9

Recently, homozygous gene deletion of GSTM1, one of the Mu class glutathione S-transferase isozymes, was found to occur in approximately half of the population of various ethnic origins and has been implicated in tobacco-related carcinogenesis. In the present study we evaluated the risk of GSTM1 null genotype for lung cancer in relation to the extent of tobacco smoke exposure in 178 lung cancer patients (157 males, 21 females) and 201 healthy controls (140 males, 61 females), who were all Japanese and current smokers aged < or = 69 at the time of diagnosis. GSTM1 genotype was determined by polymerase chain reaction. We found GSTM1 gene to be lacking in 45.3% of the control population and demonstrated that the null genotype was aggregated a lot more in the squamous and small cell carcinoma groups (63-64%) than the control group but slightly more in the adenocarcinoma group (54.3%). Furthermore, when male patients and controls were analysed in relation to the degrees (< 800, 800-1200 and > or = 1200) of smoking index (sigma (cigarettes smoked per day) x (years of smoking)], the proportion of GSTM1 null genotype was found to increase progressively in the squamous and small cell carcinoma groups from 42-50% (odds ratio 0.8-1.3) in the patients with smoking index < 800 to 72-75% (odds ratio 3.1-3.7) in the patients with smoking index > or = 1200, while it was unrelated in the adenocarcinoma (50-55%, odds ratio 1.2-1.5) and in the control groups (42-48%). These results support the hypothesis that the GSTM1 null genotype is one of the genetic traits for smoking-related lung cancers, the risk of which, however, appears to be dependent on the extent of tobacco smoke exposure.
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PMID:Lung cancer risk of GSTM1 null genotype is dependent on the extent of tobacco smoke exposure. 831 38

An association of lung cancer susceptibility with an MspI restriction site polymorphism of the CYP1A1 gene was reported in our previous study. This polymorphism has been subsequently found to be closely linked to another isoleucine-valine (Ile-Val) polymorphism, which resulted in an Ile-Val amino acid replacement in the heme-binding region of P4501A1. We report here that genetic risk for squamous cell carcinoma of the lung was associated with these two polymorphisms of the CYP1A1 gene in terms of genotype frequencies and cigarette-smoking dose and that a more increased risk was observed for the individuals with "susceptible" genotypes of CYP1A1 combined with a deficient genotype of a mu-class glutathione S-transferase (GST1), which detoxifies the electrophilic metabolites of aromatic hydrocarbon procarcinogens activated by P4501A1. We first compared the total amounts of cigarettes consumed during a lifetime among 85 patients with squamous cell carcinoma of the lung, whose CYP1A1 and GST1 genes were identified. The patients with a susceptible homozygote of each of the MspI and Ile-Val polymorphisms contracted the carcinoma after smoking fewer cigarettes than those with other genotypes. When the GST1 polymorphism was taken into account, the cumulative cigarette amounts in combined genotyping of the two genes showed distinct differences, resulting in the lowest cigarette dose observed for the patients with a susceptible MspI or Ile-Val genotype of CYP1A1 combined with a deficient GST1 homozygote. Next, a case-control study revealed that the individuals with the susceptible MspI or Ile-Val genotype combined with deficient GST1 were at remarkably high risk with an odds ratio of 16.00 or 41.00, respectively (95% confidence interval, 3.76-68.02 or 8.68-193.61, respectively), at a low dose level of cigarette smoking.
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PMID:Polymorphisms of the CYP1A1 and glutathione S-transferase genes associated with susceptibility to lung cancer in relation to cigarette dose in a Japanese population. 831 7

Japanese lung cancer patients (n = 121) and community controls (n = 201), both with current smoking history and aged < or = 69, were compared for the rates of class mu glutathione S-transferase (GSTmu) negative genotype detected by polymerase chain reaction. The prevalence of the GSTmu negative genotype was 45.3% in the community control group and 68.4%, 69.2%, 54.3% and 72.7% in the squamous cell carcinoma, small cell carcinoma, adenocarcinoma and other primary lung cancer groups, respectively. Odds ratios adjusted for age, sex composition and smoking index by multiple logistic regression analysis were 2.71 (1.23-5.99), 2.72 (1.11-6.66), 1.33 (0.68-2.60), and 3.27 (0.83-12.81), respectively. These results suggest that smokers with a GSTmu negative genotype are at higher risk for bronchial carcinoma than smokers with positive genotype.
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PMID:Increased risk of lung cancer in Japanese smokers with class mu glutathione S-transferase gene deficiency. 836 89

The human placental form of glutathione S-transferase pi (GST-pi) was measured by a sandwich enzyme-linked immunosorbent assay in lung cancer cell lines established in our laboratories. In classic-type small cell lung cancer (SCLC), variant-type SCLC and non-small cell lung cancer (NSCLC), the respective mean GST-pi values were 0.83 +/- 0.88, 3.27 +/- 2.85 and 2.40 +/- 0.76 micrograms/mg protein. Cell lines with high GST-pi content had low levels of neuron specific enolase, which is known as a representative tumor marker for SCLC. This suggests that GST-pi may also be used as a potential marker for NSCLC. The lines with low GST-pi content were more sensitive to radiation than those with high GST-pi content. Cell lines not subjected to prior therapy also showed a good correlation between GST-pi levels and chemosensitivity to cisplatin. The findings suggest that GST-pi can be used as an adjunctive marker for lung cancer.
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PMID:Glutathione S-transferase pi levels in a panel of lung cancer cell lines and its relation to chemo-radiosensitivity. 838 71

The expression of intrinsic resistance to cisplatin in two lung cancer cell lines, one derived from a small cell carcinoma (SW1271) and the other from an adenocarcinoma (A549), relative to a drug-sensitive small cell line SW900, was characterized by: (i) expression of cross-resistance to mitomycin C and cadmium chloride, but increased sensitivity to adriamycin and etoposide; (ii) significantly decreased cisplatin uptake; (iii) elevated levels of glutathione which could be reduced by buthionine L-sulfoximine resulting in significant sensitization of the cells to cisplatin; (iv) a lack of consistent modification of metallothionein content and expression of levels of glutathione S-transferase, glutathione reductase and glutathione peroxidase or of activities of DT-diaphorase or catalase; (v) significantly reduced total DNA-platination levels immediately following a 1 h cisplatin treatment with 10 micrograms/ml (33.3 microM); (vi) increased removal of Pt-GG and Pt-AG adducts by the A549 cells, consistent with increased repair capacity, but a lack of removal of these major adducts by the SW1271 cells indicative of tolerance of this drug-induced DNA damage. These data therefore provide evidence of differential formation, repair and tolerance of DNA damage following exposure of three human lung carcinoma cell lines to cisplatin.
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PMID:Evidence of differential cisplatin-DNA adduct formation, removal and tolerance of DNA damage in three human lung carcinoma cell lines. 840 Mar 52

Mammalian cytosolic glutathione S-transferases (GSTs; EC 2.5.1.18) form a supergene family consisting of four distinct families, named alpha, mu, pi and theta. In humans one member of the mu class gene family (GSTM1) has been shown to be polymorphic and is only expressed in 55-60% of individuals. Previous studies have shown a possible link with the null phenotype and susceptibility to cancer, in particular to lung cancer. In this study we genotyped individuals with breast, bladder and colorectal cancer. A total of 490 individuals with cancer were studied, and consisted of 97 bladder, 197 breast and 196 colorectal cancers. No significant differences were observed in the frequency of nulled individuals in bladder or breast cancer patients when compared with a control population of 225 individuals. However, a significant excess of nulled individuals were seen in colorectal cancer: 56.1% compared with the control group value of 41.8%. This was shown to be highly significant depending on the site of the tumours and > 70% of individuals with a tumour in the proximal colon were GSTM1 nulled. This is an approximately 2-fold increase in colon cancer risk in these individuals.
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PMID:Relationship between the GSTM1 genetic polymorphism and susceptibility to bladder, breast and colon cancer. 840 4

The isoenzyme mu of glutathione S-transferase (GST mu) is dominantly inherited and the prevalence of this isoenzyme in the population is about 60%. An increased risk of lung cancer has been previously shown among smokers lacking GST mu in (Seidegard J., Pero R.W., Miller D.G., Beattie E.J. (1986) Carcinogenesis, 7, 751-753). The frequency of the phenotypes of this isoenzyme in bladder cancer patients (n = 75), in larynx cancer patients (n = 78) and healthy controls matched for age and smoking history is reported here. A significantly higher proportion of smokers in the control group had measurable GST mu compared with bladder cancer patients (54.6% vs. 33.3%, P < 0.01) and also compared to larynx cancer patients (55.1% vs. 33.3%, P < 0.01). Odds ratio analysis indicates that smokers with this polymorphic variant have an approximately 2-fold greater risk of developing these cancers.
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PMID:Human glutathione S-transferase mu (GST mu) deficiency as a marker for the susceptibility to bladder and larynx cancer among smokers. 842 49

Glutathione S-transferase class mu (GSTM1) is known to detoxify certain carcinogens or their activated metabolites. In a previous study using phenotyping methods, individuals genetically devoid of this enzyme activity were significantly overrepresented among lung cancer patients compared to controls, suggesting that this trait is a risk factor for lung cancer. Here, GST class mu status has been determined both pheno- and genotypically, i.e., (a) by ex vivo measurement of trans-stilbene oxide conjugation in lymphocytes, (b) by GSTM1 quantification in blood using an immunoassay, and (c) by the application of polymerase chain reaction to genomic DNA with characterization of an inactivating mutation responsible for the null allele and a G/C single base allelic variance corresponding to the polymorphism of GSTM1 isoenzymes mu and psi, respectively. One hundred seventeen lung cancer patients and 155 control patients were studied. The two groups were of German origin and were similar with respect to age, sex, smoking history, and catchment area. In about 97% of cases, the three methods of assigning activity type of GSTM1 gave corresponding results. By genotype, 55 of 117 lung cancer patients (47.0%) and 73 of 155 control patients (47.1%) were GSTM1 active. The control group was confirmed by analysis of GSTM1 genotype in 200 further, independently studied reference patients; 101 of them were GSTM1 active (50.5%). Thus, the hypothesis of heritable GSTM1 deficiency as a host factor predisposing to lung cancer proved inappropriate. Detailed analysis of subgroups with respect to smoking habits, age, and sex failed to reveal an impact of GST class mu genotype on lung cancer risk. Among the total of 272 patients studied, 36 individuals carried at least one psi allele; however, no unexpected frequency distribution was observed.
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PMID:Genotype and phenotype of glutathione S-transferase class mu isoenzymes mu and psi in lung cancer patients and controls. 843 46


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