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:1.6.5.2 (NQO1)
6,196 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Biallelic somatic mutations of TCF1 coding for hepatocyte nuclear factor 1alpha (HNF1alpha) are found in 50% of the hepatocellular adenoma (HCA) cases usually associated with oral contraception. In rare cases, HNF1alpha germ line mutations could also predispose to familial adenomatosis. In order to identify new genetic factors predisposing to HNF1alpha-mutated HCA, we searched for mutations in genes involved in the metabolism of estrogen. For 10 genes (CYP1A1, CYP1A2, CYP3A4, CYP3A5, COMT, UGT2B7, NQO1, GSTM1, GSTP1, and GSTT1), we did not find mutations nor differences in the allele distribution among 32 women presenting HNF1alpha-mutated adenomas compared with 58 controls. In contrast, we identified a CYP1B1 germ line heterozygous mutation in 4 of 32 women presenting HNF1alpha-mutated adenomas compared with none in 58 controls. We confirmed these results with the identification of four additional CYP1B1 mutations in a second series of 26 cases. No mutations were found in the control group, which was extended to 98 individuals, and only a known rare genetic variant was observed in two controls (P = 0.0003). We did an ethoxyresorufin O-deethylase assay to evaluate the functional consequence of the CYP1B1 mutations. We found reduced enzymatic activity in each CYP1B1 variant. In addition, an E229K CYP1B1 mutation was found in a woman with a germ line HNF1alpha mutation in a familial adenomatosis context. In this large family, all three patients with adenomatosis bore both HNF1 and CYP1B1 germ line mutations. In conclusion, our data suggested that CYP1B1 germ line-inactivating mutations might increase the incidence of HCA in women with HNF1alpha mutations.
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PMID:Association of CYP1B1 germ line mutations with hepatocyte nuclear factor 1alpha-mutated hepatocellular adenoma. 1736 80

Various molecular epidemiological studies have been performed to find genetic etiology for lung cancer. Particularly, genetic polymorphisms in NAD(P)H-quinone oxidoreductase (NQO1), cytochrome P450 (CYP)1A1, myeloperoxidase (MPO), glutathione-S-transferase (GST)P1, GSTT1, and GSTM1, and have been suspected to affect lung cancer risk. However, there was no study that examined the combined effects of these genes on lung cancer risk. We studied the combined genetic effects on lung cancer risk in 671 Korean subjects including 318 lung cancer patients and 353 controls. They filled questionnaires, which included lifestyle and childhood- and current environment data. Based on single nucleotide polymorphisms and gene deletions, genetic polymorphisms of the above six genes were determined with PCR-RFLP and TaqMan methods. As results, genetic polymorphisms in the GSTP1, MPO, and CYP1A1 among the genetic factors showed associations with lung cancer risk. The reference, which is supposed to have the lowest risk for cancer, was subjects who were homozygous wild type of the GSTP1 and CYP1A1 and had the MPO- mutant allele. After combination study of the three gene-polymorphism, the subjects who were most different with the reference, i.e. had the mutant allele of the GSTP1 and CYP1A1 and homozygous wild type of the MPO, showed approximately 5-fold-higher risk for lung cancer than the reference (95% CI, 2.05-12.05). Therefore, our study suggests that the combination of the GSTP1, MPO, and CYP1A1 variations affects susceptibility to lung cancer.
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PMID:Combined effects of genetic polymorphisms in six selected genes on lung cancer susceptibility. 1742 72

Previous studies suggest that enzymes involved in the androgen metabolic pathway are susceptibility factors for prostate cancer. Estrogen metabolites functioning as genotoxins have also been proposed as risk factors. In this study, we systematically tested the hypothesis that common genetic variations for those enzymes involved in the androgen and estrogen metabolic pathways increase risk for sporadic and familial prostate cancer. From these two pathways, 46 polymorphisms (34 single nucleotide polymorphisms, 10 short tandem repeat polymorphisms, and 2 null alleles) in 25 genes were tested for possible associations. Those genes tested included PRL, LHB, CYP11A1, HSD3B1, HSD3B2, HSD17B2, CYP17, SRD5A2, AKR1C3, UGT2B15, AR, SHBG, and KLK3 from the androgen pathway and CYP19, HSD17B1, CYP1A1, CYP1A2, CYP1B1, COMT, GSTP1, GSTT1, GSTM1, NQO1, ESR1, and ESR2 from the estrogen pathway. A case-control study design was used with two sets of cases: familial cases with a strong prostate cancer family history (n = 438 from 178 families) and sporadic cases with a negative prostate cancer family history (n = 499). The controls (n = 493) were derived from a population-based collection. Our results provide suggestive findings for an association with either familial or sporadic prostate cancer with polymorphisms in four genes: AKR1C3, HSD17B1, NQO1, and GSTT1. Additional suggestive findings for an association with clinical variables (disease stage, grade, and/or node status) were observed for single nucleotide polymorphisms in eight genes: HSD3B2, SRD5A2, SHBG, ESR1, CYP1A1, CYP1B1, GSTT1, and NQO1. However, none of the findings were statistically significant after appropriate corrections for multiple comparisons. Given that the point estimates for the odds ratio for each of these polymorphisms are <2.0, much larger sample sizes will be required for confirmation.
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PMID:Evaluation of genetic variations in the androgen and estrogen metabolic pathways as risk factors for sporadic and familial prostate cancer. 1750 24

Phase II detoxification enzymes are responsible for the detoxification and elimination of activated carcinogens, and thus act as important biomarkers for chemoprevention. In this study, we tested the chemopreventive activity of taxifolin, a flavanon compound purified from a mongolian medicinal plant, by measuring quinone reductase (QR) activity in HCT 116 cells. Taxifolin induced significant QR activity, but displayed relatively low cytotoxicity in cells (chemoprevention index=5.75). To identify the target genes regulated by taxifolin, DNA microarray was performed with a 3K human cancer chip containing 3096 human genes associated with carcinogenesis. Significant analysis of microarray (SAM) revealed 428 differentially expressed (DE) genes as statistically significant, with a false discovery rate (FDR) of 57.2% (delta=0.3366). Sixty-five genes, including a few detoxification enzymes (NQO1, GSTM1) and an antioxidant enzyme (TXNRD1), were up-regulated and 363 genes were down-regulated in the presence of 60 microM taxifolin. In view of the finding that selected genes of interest contained antioxidant response element (ARE), we hypothesize that taxifolin modulates chemopreventive genes through activation of the ARE. Transient transfection experiments using the ARE QR-CAT construct demonstrate that taxifolin significantly activates ARE, but not xenobiotic response element (XRE). In conclusion, taxifolin acts as a potential chemopreventive agent by regulating genes via an ARE-dependent mechanism.
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PMID:The chemopreventive effect of taxifolin is exerted through ARE-dependent gene regulation. 1754 Nov 56

The work studied possible association between genetic polymorphisms of CYP2D6, GSTM1, GSTT1and NQO1 and altered susceptibility to leukaemia, correlating these genetic polymorphisms with clinical prognostic data, response to therapy and relapse. The study included 32 leukaemia patients, 19 with acute myeloid leukemia (AML) and 13 with acute lymphoid leukaemia (ALL), and 11 normal individuals (control group). Basic investigations for the diagnosis of AML and ALL were performed, including blood picture, bone marrow aspirate, cytochemistry and immunophenotyping for detection of subtypes. Detection of CYP2D6, NQO1, GSTM1 and GSTT1 genetic polymorphisms used a polymerase chain reaction-restriction fragment length polymorphism. A follow-up was made for association between the outcome of patients and different patterns of genetic polymorphisms. Results demonstrate a significant increase in the frequency of CYP2D6 wild-type and GSTM1 null genotypes in the acute leukaemia group compared with the control. Studying the relationship between polymorphisms of these genes and the outcome of our cases revealed the wild genotype of CYP2D6 significantly influenced the outcome of acute leukaemia particularly in AML cases, while GSTM1 null genotype was associated with bad prognosis among the ALL group. The study also revealed that patients with combined mutant CYP2D6/present GSTM1/present GSTT1 achieved the best prognosis, suggesting synergistic impact of these genetic polymorphisms on the outcome of acute leukaemia cases. This case-control study suggests a contribution of CYP2D6 and GSTM1 null variants in the development of acute leukaemia. In addition, GSTM1 and GSTT1 genotypes were apparently related to response, side effects and prognosis of patients with AML.
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PMID:Study of genetic polymorphism of xenobiotic enzymes in acute leukemia. 1758 25

Chronic exposure to ozone (O(3)) can cause changes in lung function that may reflect remodelling of small airways. It is likely that antioxidant enzyme function affects susceptibility to O(3). The aim of the present study was to determine whether polymorphisms in antioxidant enzyme (GSTM1, GSTP1 and NQO1) genes affect the risk of lung function changes related to chronic exposure to O(3). In total, 210 young adults who participated in a previous study, which showed a relationship between lifetime exposure to O(3) and decreased lung function, were genotyped. Multivariable linear regression was used to model sex-specific associations between genotypes and O(3)-related lung function changes, adjusting for height, weight, lifetime exposure to nitrogen dioxide and particles with a 50% cut-off aerodynamic diameter of 10 mum, and self-identified race/ethnicity. The GSTM1-null/NQO1 Pro187Pro-combination genotype was significantly associated with increased risk of an O(3)-related decrease in mean forced expiratory flow between 25-75% of forced vital capacity in females (parameter estimate+/-se -75+/-35 mL.s(-1)), while the GSTP1 Val105 variant genotypes were significantly associated with greater risk of an O(3)-related decrease in mean forced expiratory flow at 75% of forced vital capacity in males (-81+/-31 mL.s(-1)). GSTM1-null status was not significantly associated with any O(3)-related changes in lung function in either sex. The current authors conclude that the effects of antioxidant enzyme gene polymorphisms on the risk of decreased lung function related to chronic exposure to ozone may be modified by sex-specific factors.
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PMID:Effects of antioxidant enzyme polymorphisms on ozone-induced lung function changes. 1765 11

The present study is aimed at evaluating the genotype frequency of detoxifying genes such as GSTM1, GSTT1 and NQO1 in Maharastrian population of central India. The study revealed about 64.6% of GSTM1-positive and 35.4% GSTM1-null population. GSTT1-positive genotype was found to be 87.5% and GSTT1-null showed 12.5%. The NQO1 genotype of Maharastrian population showed 52.3% of C/C, 42.48% C/T and 5.18% T/T. The NQO1 of this population does not deviate from the expected Hardy-Weinberg equilibrium. The genotype frequencies GSTM1 and GSTT1 of the population when compared with other ethnic groups of Asia and Caucasians show distinct nature of Maharastrian population from other Asian and Caucasian population.
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PMID:Distribution of detoxifying genes polymorphism in Maharastrian population of central India. 1786 25

Using generalized linear models with natural-spline smoothing functions, we detected effects of specific xenobiotic metabolizing genes and gene-environment interactions on levels of benzene metabolites in 250 benzene-exposed and 136 control workers in Tianjin, China (for all individuals, the median exposure was 0.512 p.p.m. and the 10th and 90th percentiles were 0.002 and 6.40 p.p.m., respectively). We investigated five urinary metabolites (E,E-muconic acid, S-phenylmercapturic acid, phenol, catechol, and hydroquinone) and nine polymorphisms in seven genes coding for key enzymes in benzene metabolism in humans {cytochrome P450 2E1 [CYP2E1, rs2031920], NAD(P)H: quinone oxidoreductase [NQO1, rs1800566 and rs4986998], microsomal epoxide hydrolase [EPHX1, rs1051740 and rs2234922], glutathione-S-transferases [GSTT1, GSTM1 and GSTP1(rs947894)] and myeloperoxidase [MPO, rs2333227]}. After adjusting for covariates, including sex, age, and smoking status, NQO1*2 (rs1800566) affected all five metabolites, CYP2E1 (rs2031920) affected most metabolites but not catechol, EPHX1 (rs1051740 or rs2234922) affected catechol and S-phenylmercapturic acid, and GSTT1 and GSTM1 affected S-phenylmercapturic acid. Significant interactions were also detected between benzene exposure and all four genes and between smoking status and NQO1*2 and EPHX1 (rs1051740). No significant effects were detected for GSTP1 or MPO. Results generally support prior associations between benzene hematotoxicity and specific gene mutations, confirm earlier evidence that GSTT1 affects production of S-phenylmercapturic acid, and provide additional evidence that genetic polymorphisms in NQO1*2, CYP2E1, and EPHX1 (rs1051740 or rs2234922) affect metabolism of benzene in the human liver.
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PMID:Genetic polymorphisms and benzene metabolism in humans exposed to a wide range of air concentrations. 1788 17

Polymorphisms in genes coding xenobiotic-metabolizing enzymes are considered as risk factors modifying susceptibility to cancer. We developed a biochip for the analysis of 18 mutations in 10 genes of metabolizing system: CYP1A1, CYP2D6, GSTT1, GSTM1, MTHFR, MTRR, NQO1, CYP2C9, CYP2C19, and NAT2. Using allele-specific hybridization on the biochip 76 T-cell non-Hodgkin's lymphoma (NHL) patients, 83 B-cell chronic lymphocytic leukemia (B-CLL) patients, and 177 healthy donors were tested. Polymorphic CYP1A1 alleles were more frequent in B-CLL patients relative to normal controls, for example, a combination of polymorphic variants 4887C > A, 4889A > G, and 6235T > C (OR = 1.76, 95% CI = 1.0-3.1). The GSTM1 null genotype was more frequent in NHL patients relative to controls (OR = 1.82, 95% CI = 1.1-3.1). The combination of unfavorable polymorphic CYP1A1 variants and GSTM1 null genotype was found more frequently in B-CLL patients relative to controls (OR = 2.52, 95% CI = 1.3-4.9). In addition, male B-CLL patients demonstrated a significantly increased occurrence of heterozygous and homozygous allele *2 of CYP2C9 gene (OR = 2.38, 95% CI = 1.1-5.2) as well as a combination of alleles *2 and *3 of the gene (OR = 2.09, 95% CI = 1.1-3.9). Thus, our findings show the association between polymorphic alleles of CYP1A1, GSTM1, and CYP2C9 genes and the risk to develop NHL or B-CLL. The developed biochip can be considered as a convenient analytical tool for research studies and predictive analysis in oncohematology.
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PMID:Polymorphisms in xenobiotic-metabolizing genes and the risk of chronic lymphocytic leukemia and non-Hodgkin's lymphoma in adult Russian patients. 1806 41

The last four decades have seen significant increase in the incidence of non-Hodgkin lymphoma (NHL) as a possible result of increasing environmental carcinogens exposure. Based on the increasing evidence for the association between carcinogen-exposure-related cancer risk and xenobiotic gene polymorphisms, we have undertaken a hospital based case-control study on xenobiotic gene polymorphisms in Saudi individuals with a diagnosis of diffuse large B-cell lymphoma (DLBCL). Polymorphisms in five genes (CYP1A1, GSTT1, GSTP1, GSTM1, and NQO1) were characterized in 182 individuals with DLBCL and 513 normal controls using PCR-RFLP method. The CYP1A1*2C (p = 0.011, OR: 6.62, and 95% CI: 1.56-28.10), GSTT1 null (p < or = 0.001, OR: 11.94, 95% CI: 7.88-18.12), and GSTP1 TT genotypes (p = 0.017, OR: 3.42, 95% CI 1.26-9.38) demonstrated significant association of DLBCL risk. None of the other alleles tested for proved to be significant indicators of DLBCL risk. Our findings suggest that polymorphisms of xenobiotic metabolizing enzyme genes may modify the individual susceptibility to develop DLBCL in Saudi Arabian population.
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PMID:Polymorphisms of drug-metabolizing enzymes CYP1A1, GSTT and GSTP contribute to the development of diffuse large B-cell lymphoma risk in the Saudi Arabian population. 1820 21


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