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dc.contributor.authorLewis, Sarah J
dc.contributor.authorCherry, Nicola M
dc.contributor.authorNiven, Robert McL
dc.contributor.authorBarber, Philip V
dc.contributor.authorPovey, Andrew C
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.
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
html.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.


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