Polymorphisms in the NAD(P)H: quinone oxidoreductase gene and small cell lung cancer risk in a UK population.

2.50
Hdl Handle:
http://hdl.handle.net/10541/85734
Title:
Polymorphisms in the NAD(P)H: quinone oxidoreductase gene and small cell lung cancer risk in a UK population.
Authors:
Lewis, Sarah J; Cherry, Nicola M; Niven, Robert McL; Barber, Philip V; Povey, Andrew C
Abstract:
NAD(P)H: quinone oxidoreductase (NQO1) protects the cell against cytotoxicity by reducing the concentration of free quinone available for single electron reduction. The NQO1 gene is polymorphic and the variant protein exhibits just 2% of the enzymatic activity of the wildtype protein. In this study, we investigated NQO1 genotype in relation to lung cancer risk in patients attending a Manchester bronchoscopy clinic. The cases were patients with a current, or history of, malignant tumour of the lung, trachea or bronchus. The control group were all other patients attending the clinic who had never been diagnosed with a tumour. DNA extraction from bronchial lavage or blood samples and genotyping was successfully carried out for 82 of the cases and 145 controls. Patients carrying at least one variant allele were found to have almost a 4-fold increased risk of developing small cell lung cancer (adjusted OR=3.80, 95% C.I. 1.19-12.1). No association between NQO1 genotypes and non-small cell lung cancer risk was found. Furthermore, the excess small cell lung cancer risk associated with non-wildtype NQO1 genotypes was only apparent in heavy smokers where there was a >10-fold increased risk (adjusted OR=12.5, 95% C.I. 2.1-75.5). These results suggest that the NQO1 protein may be involved in the detoxification of those carcinogens associated with the development of small cell lung cancer. Individuals with reduced enzyme activity, due to a polymorphism in this gene, may therefore have an increased risk of developing this disease.
Affiliation:
School of Epidemiology and Health Sciences, Medical School, University of Manchester, Oxford Road, Manchester M139PT, UK.
Citation:
Polymorphisms in the NAD(P)H: quinone oxidoreductase gene and small cell lung cancer risk in a UK population. 2001, 34 (2):177-83 Lung Cancer
Journal:
Lung Cancer
Issue Date:
Nov-2001
URI:
http://hdl.handle.net/10541/85734
PubMed ID:
11679176
Type:
Article
Language:
en
ISSN:
0169-5002
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorLewis, Sarah Jen
dc.contributor.authorCherry, Nicola Men
dc.contributor.authorNiven, Robert McLen
dc.contributor.authorBarber, Philip Ven
dc.contributor.authorPovey, Andrew Cen
dc.date.accessioned2009-11-10T09:23:35Z-
dc.date.available2009-11-10T09:23:35Z-
dc.date.issued2001-11-
dc.identifier.citationPolymorphisms in the NAD(P)H: quinone oxidoreductase gene and small cell lung cancer risk in a UK population. 2001, 34 (2):177-83 Lung Canceren
dc.identifier.issn0169-5002-
dc.identifier.pmid11679176-
dc.identifier.urihttp://hdl.handle.net/10541/85734-
dc.description.abstractNAD(P)H: quinone oxidoreductase (NQO1) protects the cell against cytotoxicity by reducing the concentration of free quinone available for single electron reduction. The NQO1 gene is polymorphic and the variant protein exhibits just 2% of the enzymatic activity of the wildtype protein. In this study, we investigated NQO1 genotype in relation to lung cancer risk in patients attending a Manchester bronchoscopy clinic. The cases were patients with a current, or history of, malignant tumour of the lung, trachea or bronchus. The control group were all other patients attending the clinic who had never been diagnosed with a tumour. DNA extraction from bronchial lavage or blood samples and genotyping was successfully carried out for 82 of the cases and 145 controls. Patients carrying at least one variant allele were found to have almost a 4-fold increased risk of developing small cell lung cancer (adjusted OR=3.80, 95% C.I. 1.19-12.1). No association between NQO1 genotypes and non-small cell lung cancer risk was found. Furthermore, the excess small cell lung cancer risk associated with non-wildtype NQO1 genotypes was only apparent in heavy smokers where there was a >10-fold increased risk (adjusted OR=12.5, 95% C.I. 2.1-75.5). These results suggest that the NQO1 protein may be involved in the detoxification of those carcinogens associated with the development of small cell lung cancer. Individuals with reduced enzyme activity, due to a polymorphism in this gene, may therefore have an increased risk of developing this disease.en
dc.language.isoenen
dc.subjectLung Canceren
dc.subject.meshAged-
dc.subject.meshAlleles-
dc.subject.meshCarcinogens-
dc.subject.meshCarcinoma, Small Cell-
dc.subject.meshCase-Control Studies-
dc.subject.meshFemale-
dc.subject.meshGenotype-
dc.subject.meshHumans-
dc.subject.meshLung Neoplasms-
dc.subject.meshMale-
dc.subject.meshMiddle Aged-
dc.subject.meshNAD(P)H Dehydrogenase (Quinone)-
dc.subject.meshPolymerase Chain Reaction-
dc.subject.meshPolymorphism, Genetic-
dc.subject.meshQuinone Reductases-
dc.subject.meshRisk Factors-
dc.titlePolymorphisms in the NAD(P)H: quinone oxidoreductase gene and small cell lung cancer risk in a UK population.en
dc.typeArticleen
dc.contributor.departmentSchool of Epidemiology and Health Sciences, Medical School, University of Manchester, Oxford Road, Manchester M139PT, UK.en
dc.identifier.journalLung Canceren

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