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)

To explore the potential role for estrogen in lung cancer susceptibility, candidate single-nucleotide polymorphism (SNPs) in tobacco and estrogen metabolism genes were evaluated. Population-based cases (n = 504) included women aged 18-74, diagnosed with NSCLC in metropolitan Detroit between November 2001 and October 2005. Population-based controls (n = 527) were identified through random digit dialing and matched on race and age. Eleven SNPs in 10 different genes were examined in relation to risk: CYP1A1 Msp1, CYP1A1 Ile462Val, CYP1B1 Leu432Val, CYP17, CYP19A1, XRCC1 Gln399Arg, COMT Val158Met, NQO1 Pro187Ser, GSTM1, GSTT1 and GSTP1 Ile105Val. Lung cancer risk associated with individual SNPs was seen for GSTP1 [A allele; odds ratio (OR) = 1.85; 95% confidence interval (CI), 1.04-3.27] and XRCC1 (A/A genotype; OR = 1.68; 95% CI, 1.01-2.79) in white women and CYP1B1 (G allele; OR = 11.1; 95% CI, 1.18-104) in black women smokers. White women smokers carrying two risk genotypes at the following loci were at increased risk of lung cancer compared with individuals not carrying risk alleles at these loci: CYP17 and GSTM1, COMT and GSTM1, CYP17 and GSTT1, XRCC1 and GSTP1, CYP1B1 and XRCC1 and COMT and XRCC1. The most parsimonious model of lung cancer risk in white smoking women included age, family history of lung cancer, history of chronic lung disease, pack-years, body mass index, XRCC1 A/A genotype, GSTM1 null and COMT A/G or G/G genotype. These findings support the need for continued study of estrogen in relation to lung cancer risk. Polymorphisms in the tobacco metabolism, estrogen metabolism and DNA repair pathways will be useful in developing more predictive models of individual risk.
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PMID:Tobacco and estrogen metabolic polymorphisms and risk of non-small cell lung cancer in women. 1917 90

In this study, frequencies of the polymorphic variants of the genes encoding antioxidant enzymes, GSTM1, GSTT1, GSTP1, CAT, GPX1, NQO1, SOD1, and SOD3 were examined in three ethnic groups of healthy subjects from the Republic of Bashkortostan (Russians, Tatars, and Bashkirs). An association of these markers with the development of chronic obstructive pulmonary disease (COPD) was tested. Interethnic differences relative to the distribution of the polymorphic variants of the GSTP1 locus Ile105Val and the NQO1 locus 609C/T were revealed. Relative to the genotype distribution at the Ile 105Val locus of the GSTP1 gene, ethnic group of Bashkirs was found to be statistically significantly different from Tatars (chi2 = 8.819; d.f. = 2; P = 0.012). Relative to the genotype frequency distribution pattern at the NQO1 locus 609C/T, the group of Bashkirs differed from Russians (chi2 = 8.913; df. = 2; P = 0.012). An association of genotype Val/Val of the GSTP1 Ile105Val locus with the risk of COPD in Russians (chi2 = 5.25; P = 0.022; Pcor = 0.044; OR = 4.09), and of the GSTP1 haplotype *D in Tatars, was demonstrated (chi2 = 11.575; P = 0.0014; Pcor = 0.0042; OR = 3.178). Genotype TT of the CAT -262C/T locus marked resistance to the COPD development in Russians (chi2 = 6.82; P = 0.0098; Pcor = = 0.0196; OR = 0.31; 95% CI, 0.119 to 0.77). The risk for COPD in the ethnic group of Tatars was associated with the CAT haplotype (-262)C(1167)T (chi2 = 6.038; P = 0.0147; Pcor = 0.044; OR = 1.71). Analysis of the NQO1 haplotypes at the 465C/T and6009C/T loci showed that haplotype 465C/609T was associated with COPD in Russians (chi2 = 4.571; P = 0.0328; Pcor = 0.01; OR = 1.799). It was demonstrated that Gly allele of the Arg213Gly polymorphic locus of the SOD3 gene marked the risk for COPD in the ethnic group of Tatars (OR = 2.23; 95% CI, 1.22 to 4.1). Thus, GSTP1, CAT, NQO1, and SOD3 polymorphisms play an important role in the development of COPD among the population of Bashkortostan.
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PMID:[Polymorphism of the genes for antioxidant defense enzymes and their association with the development of chronic obstructive pulmonary disease in the population of Bashkortostan]. 1970 49

We have developed a gas chromatography-mass spectrometry method for analysis of benzene (BZ) metabolites in human urine and blood. Here we describe peripheral blood concentrations of hydroquinone (HQ(1)) and catechol (CAT(2)) in total, protein-bound, and unbound (free) forms obtained from BZ-exposed factory workers and controls. Total and unbound metabolites were directly measured in independent experiments, while bound forms were calculated as [total]-[unbound]. In this subset of a larger study, breathing zone benzene, toluene, and xylene were measured for the duration of a workshift, and end-shift blood samples taken from 143 subjects and controls. Potential lifestyle and environmental influences were assessed by questionnaire and bioassay, and single nucleotide polymorphisms in xenobiotic metabolizing enzymes NQO1, MPO, CYP2E1, and GSTT1 were also analyzed for potential contribution to differences in blood metabolite concentration. Total CAT, bound CAT, total HQ, and bound HQ correlated well with benzene exposure, while unbound CAT and HQ displayed no correlation. Nearly all of the metabolites found in blood were bound to protein (CAT 96-99+%, HQ 78-92+%), and when the ratio of bound to unbound metabolites were compared in subsets of exposed workers, the increase in blood metabolite concentration was nearly all due to an increase in the protein-bound molecule. These findings suggest that a threshold for conjugation does not exist within the exposure spectrum studied (0.01-78.8 mg/m(3)). This method demonstrates the feasibility of analyzing benzene metabolites in human blood, and should allow for further investigation of the health effects of benzene and its metabolites.
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PMID:Analysis of hydroquinone and catechol in peripheral blood of benzene-exposed workers. 2002 93

The hematotoxic effects of benzene exposure may be important in the occurrence of subsequent health effects. We sought to provide further information on peripheral blood effects by studying 928 workers in five factories in and around Shanghai, China exposed to a wide range of benzene concentrations. Specifically, we sought to investigate which blood indices are more strongly related to benzene exposure and which concentration levels of benzene result in peripheral blood changes. Lifestyle habits and demographic information was obtained via questionnaire, and potentially important genetic influences were determined by assessing single nucleotide polymorphisms in four genes (NQO1, MPO, CYP2E1, GSTT1). Weekly benzene exposure estimated from individual monitoring results ranged from 0.07 to 872 mg/m(3) with a median value of 7.4 mg/m(3). Twelve peripheral blood indices were examined. Stronger effects on peripheral blood were seen for red cell indices such as anemia and macrocytosis, albeit at higher (>10 ppm) exposure levels. The most sensitive parameters to benzene appeared to be neutrophils and the mean platelet volume (MPV), where effects were seen for benzene air concentrations of 7.8-8.2 ppm. Toluene exposure is a potential confounder for some peripheral blood effects, pointing to the need to scrutinize levels of both compounds in the occupational environment.
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PMID:Peripheral blood effects in benzene-exposed workers. 2003 84

A protective role of glucosinolates in prostate cancer development might be mediated by the induction of biotransformation enzymes. These enzymes, enhancing the elimination of carcinogens from the body, are known to be polymorphic. Therefore, we evaluated whether a possible association between glucosinolate intake and prostate cancer risk is modified by polymorphisms in GSTT1, GSTM1, GSTA1, GSTP1, or NOQ1 genes. A case-control study including 248 prostate cancer cases and 492 matched controls was nested in the prospective European Prospective Investigation into Cancer and Nutrition-Heidelberg cohort. At baseline, participants provided dietary and lifestyle data and blood samples, which were used for genotyping and measurement of serum glutathione S-transferase-alpha concentration. Odds ratios and 95% confidence intervals were calculated by conditional logistic regression. We found an inverse association of glucosinolate intake with prostate cancer risk (adjusted odds ratio, 0.72 per 10 mg/d increment; 95% confidence interval, 0.53-0.96). Stratification by genotype showed significantly reduced risks for subjects with wild-type of NQO1 (C609T) compared with CT or TT carriers (P(interaction) = 0.04). Those with deletions in both GSTM1 and GSTT1 genes combined had a significantly reduced risk with increasing glucosinolate intake (P(interaction) = 0.01). There was no effect modification of glucosinolate intake and cancer risk by GSTA1 (G-52A) or GSTP1 (A313G) genotype, but serum glutathione S-transferase-alpha concentrations were inversely associated with prostate cancer. This study showed that the inverse association between glucosinolate intake and prostate cancer risk was modified by NQO1 (C609T) and GSTM1 and GSTT1 deletion polymorphisms. This information will help to further elucidate the mechanism of action of potentially protective substances in vivo.
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PMID:Dietary glucosinolate intake, polymorphisms in selected biotransformation enzymes, and risk of prostate cancer. 2005 32

Early-onset lung cancer diagnosed up to the age of 50 is a very rare disease, with an increasing incidence rate. Differences in aetiology, characteristics and epidemiology of early and older onset lung cancer have been described previously, suggesting the importance of genetic factors in early-onset lung cancer aetiology. A case-control study was conducted to investigate the effects of genetic polymorphisms in the MPO, EPHX1, GSTT1, GSTM1, GSTP1 and NQO1 genes on the risk of early-onset lung cancer development. Six hundred thirty-eight Caucasian patients under the age of 51 with confirmed primary lung cancer and 1,300 cancer free control individuals, matched by age and sex, were included in this analysis. Seventeen single nucleotide polymorphisms and two deletion polymorphisms were genotyped. No significant association was found for any of the analyzed polymorphisms and overall lung cancer risk. Nonsignificantly decreased risk of lung cancer was observed for carriers of 1 or 2 copies of GSTM1. Subgroup analysis revealed gender- and/or smoking-specific effects of EPHX1 rs2854455 (IV-1464C > T) and rs2234922 (His139Arg), GSTT1 deletion, GSTP1 rs1695 (Ile105Val), rs947895 (+991C > A) and rs4891 (Ser185Ser) and NQO1 rs1800566 (Pro187Ser) polymorphisms. However, none of the observed effects were confirmed by interaction tests nor were they significant after Bonferroni correction for multiple testing. In summary, our study suggested a modifying effect of polymorphisms in EPHX1, GSTP1, GSTT1, GSTM1 and NQO1 genes on the risk of early-onset lung cancer. To confirm these observations and to eliminate possible bias in our analyses, larger studies are warranted.
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PMID:Genetic polymorphisms of MPO, GSTT1, GSTM1, GSTP1, EPHX1 and NQO1 as risk factors of early-onset lung cancer. 2009 63

This study investigated nucleic acid oxidation associated with exposure to benzene at low levels in 239 workers recruited among traffic policemen, taxi drivers and gasoline pump attendants of the city of Parma (Italy). Biomarkers of exposure, namely urinary t,t-muconic acid (t,t-MA) and S-phenylmercapturic acid (S-PMA), urinary cotinine, and urinary biomarkers of nucleic acid oxidation, namely 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo), 8-oxo-7,8-dihydroguanosine (8-oxoGuo) and 8-oxo-7,8-dihydroguanine (8-oxoGua) were determined by liquid chromatography-tandem mass spectrometry. Relevant polymorphisms of NAD(P)H:quinone oxidoreductase (NQO1), glutathione S-transferases M1-1 (GSTM1), T1-1 (GSTT1), and A1 (GSTA1) were characterized by polymerase chain reaction-based methods in a subgroup of subjects. Biomarkers of nucleic acid oxidation were correlated with each other (r> or =0.32, p<0.0001) and with exposure biomarkers (r> or =0.28, p<0.0001). Multiple linear regression models including age, sex and smoking habits as independent variables demonstrated that benzene exposure is associated with oxidation damage to nucleic acid, particularly to RNA (p<0.0001) and is modulated by the NQO1 polymorphism. The study confirmed a significant modulating effect of GSTM1 (p=0.010), GSTT1 (p=0.023) and GSTA1 (p=0.048) polymorphisms on S-PMA excretion, with a significant interaction between GSTM1 and both GSTT1 and GSTA1 (p=0.006 and p=0.037, respectively).
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PMID:Occupational exposure to low levels of benzene: Biomarkers of exposure and nucleic acid oxidation and their modulation by polymorphic xenobiotic metabolizing enzymes. 2010 May 51

Xenobiotic-metabolizing genes (e.g., Cytochromes P450, GST, NAT2, and NQO1), folate metabolism genes (e.g., MTHFR and MTRR), and major histocompatibility complex genes (e.g., HLA-DQA1) play multiple roles in the organism functioning. In addition, AB0 is the most clinically significant high-polymorphic gene in transfusion and transplantation medicine. Epidemiological data show that allele frequencies of these genes exhibit ethnic and geographic diversity. Besides, little is known about frequency distribution of the major polymorphic variants in native Russians. We developed biological microchips that allow us to analyze a spectrum of allelic variants in 12 different genes: CYP1A1, CYP2D6, CYP2C9, CYP2C19, GSTT1, GSTM1, MTHFR, MTRR, NQO1, NAT2, HLA-DQA1, and AB0. Using this composite methodological platform we have studied 352 DNA samples from healthy native Russian volunteers. The allelic frequencies of gene polymorphisms obtained are close to allelic frequencies observed in some European populations, as published earlier. These data were used in comparative studies to determine predisposition to tuberculosis, lymphoma, and leukemia in adults and to childhood acute leukemia. The HLA-DQA1 and AB0 allele frequencies were used to estimate forensic population parameters for these loci.
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PMID:Microarray-based detection of CYP1A1, CYP2C9, CYP2C19, CYP2D6, GSTT1, GSTM1, MTHFR, MTRR, NQO1, NAT2, HLA-DQA1, and AB0 allele frequencies in native Russians. 2037 52

The polymorphism of CYP1A1*2A or CYP1A1*2B, and the linkage of CYP1A1*2A, CYP1A1*2B, GSTM1 and GSTT1 polymorphisms have been established as susceptible genes or gene-gene interactions of tobacco-related lung cancer. New candidate genes susceptible for lung cancer such as NQO1 (NAD(P)H:quinine oxidoreductase), NAT2 (N-acetyltransferase 2), and several others have been reported. In the present review we focus on new candidate genes susceptible for lung cancer, then examine all Japanese references by meta-analysis on susceptible genes over the past 20 years, and discuss whether new candidates and changing trend in Japan could be caused by environmental change.
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PMID:Additional candidates to conventional genes susceptible for lung cancer and changing trend in Japan. 2042 2

A case-control study of genetic, environmental, and occupational risk factors for Parkinson's disease (PD) was carried out in five European countries (Italy, Malta, Romania, Scotland, and Sweden) to explore the possible contribution of interactions among host and environmental factors in sporadic PD. Whereas smoking habits confirmed its negative association with PD, a possible modulatory role of genetic polymorphisms was investigated to obtain further mechanistic insights. We recruited 767 cases of PD and 1989 age-matched and gender-matched controls. Participants completed an interviewer-administered questionnaire including the history of smoking habits. The polymorphisms of genes involved either in metabolism of compounds contained in tobacco smoke (CYP2D6, CYP1B1, GSTM1, GSTT1, GSTM3, GSTP1, NQO1, SOD2, EPHX and NAT2) or in dopaminergic neurotransmission (MAOA, MAOB, DAT1 and DRD2) were characterized by PCR based methods on genomic DNA. We found evidence of statistically significant gene-tobacco interaction for GSTM1, NAT2, and GSTP1, the negative association between tobacco smoking and PD being significantly enhanced in subjects expressing GSTM1-1 activity, in NAT2 fast acetylators, and in those with the GSTP1*B*C haplotype. Owing to the retrospective design of the study, these results require confirmation.
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PMID:A case-control study of Parkinson's disease and tobacco use: gene-tobacco interactions. 2046 8


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