2.50
Hdl Handle:
http://hdl.handle.net/10541/70378
Title:
Lung cancer risk and variation in MGMT activity and sequence.
Authors:
Povey, Andrew C; Margison, Geoffrey P; Santibanez-Koref, Mauro F
Abstract:
O(6)-Alkylguanine-DNA alkyltransferase (MGMT) repairs DNA adducts that result from alkylation at the O(6) position of guanine. These lesions are mutagenic and toxic and can be produced by a variety of agents including the tobacco-specific nitrosamines, carcinogens present in cigarette smoke. Here, we review some of our work in the context of inter-individual differences in MGMT expression and their potential influence on lung cancer risk. In humans there are marked inter-individual differences in not only levels of DNA damage in the lung (N7-methylguanine) that can arise from exposure to methylating agents but also in MGMT activity in lung tissues. In the presence of such exposure, this variability in MGMT activity may alter cancer susceptibility, particularly as animal models have demonstrated that the complete absence of MGMT activity predisposes to alkylating-agent induced cancer while overexpression is protective. Recent studies have uncovered a series of polymorphisms that affect protein activity or are associated with differences in expression levels. The associations between these (and other) polymorphisms and cancer risk are inconsistent, possibly because of small sample sizes and inter-study differences in lung cancer histology. We have recently analysed a consecutive series of case-control studies and found evidence that lung cancer risk was lower in subjects with the R178 allele.
Affiliation:
Centre for Occupational and Environmental Health, University of Manchester, United Kingdom. a.povey@manchester.ac.uk
Citation:
Lung cancer risk and variation in MGMT activity and sequence. 2007, 6 (8):1134-44 DNA Repair
Journal:
DNA Repair
Issue Date:
1-Aug-2007
URI:
http://hdl.handle.net/10541/70378
DOI:
10.1016/j.dnarep.2007.03.022
PubMed ID:
17569600
Type:
Article
Language:
en
ISSN:
1568-7864
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorPovey, Andrew C-
dc.contributor.authorMargison, Geoffrey P-
dc.contributor.authorSantibanez-Koref, Mauro F-
dc.date.accessioned2009-06-12T14:25:14Z-
dc.date.available2009-06-12T14:25:14Z-
dc.date.issued2007-08-01-
dc.identifier.citationLung cancer risk and variation in MGMT activity and sequence. 2007, 6 (8):1134-44 DNA Repairen
dc.identifier.issn1568-7864-
dc.identifier.pmid17569600-
dc.identifier.doi10.1016/j.dnarep.2007.03.022-
dc.identifier.urihttp://hdl.handle.net/10541/70378-
dc.description.abstractO(6)-Alkylguanine-DNA alkyltransferase (MGMT) repairs DNA adducts that result from alkylation at the O(6) position of guanine. These lesions are mutagenic and toxic and can be produced by a variety of agents including the tobacco-specific nitrosamines, carcinogens present in cigarette smoke. Here, we review some of our work in the context of inter-individual differences in MGMT expression and their potential influence on lung cancer risk. In humans there are marked inter-individual differences in not only levels of DNA damage in the lung (N7-methylguanine) that can arise from exposure to methylating agents but also in MGMT activity in lung tissues. In the presence of such exposure, this variability in MGMT activity may alter cancer susceptibility, particularly as animal models have demonstrated that the complete absence of MGMT activity predisposes to alkylating-agent induced cancer while overexpression is protective. Recent studies have uncovered a series of polymorphisms that affect protein activity or are associated with differences in expression levels. The associations between these (and other) polymorphisms and cancer risk are inconsistent, possibly because of small sample sizes and inter-study differences in lung cancer histology. We have recently analysed a consecutive series of case-control studies and found evidence that lung cancer risk was lower in subjects with the R178 allele.en
dc.language.isoenen
dc.subjectLung Canceren
dc.subjectTumour Suppressor Proteinsen
dc.subject.meshAlkylating Agents-
dc.subject.meshAnimals-
dc.subject.meshDNA Damage-
dc.subject.meshDNA Modification Methylases-
dc.subject.meshDNA Repair Enzymes-
dc.subject.meshGenetic Variation-
dc.subject.meshGuanine-
dc.subject.meshHumans-
dc.subject.meshLung-
dc.subject.meshLung Neoplasms-
dc.subject.meshPolymorphism, Genetic-
dc.subject.meshRisk Factors-
dc.subject.meshTumor Suppressor Proteins-
dc.titleLung cancer risk and variation in MGMT activity and sequence.en
dc.typeArticleen
dc.contributor.departmentCentre for Occupational and Environmental Health, University of Manchester, United Kingdom. a.povey@manchester.ac.uken
dc.identifier.journalDNA Repairen

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