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dc.contributor.authorCrosbie, Philip A J
dc.contributor.authorMcGown, Gail
dc.contributor.authorThorncroft, Mary R
dc.contributor.authorO'Donnell, Paul
dc.contributor.authorBarber, Philip V
dc.contributor.authorLewis, Sarah J
dc.contributor.authorHarrison, Kathryn L
dc.contributor.authorAgius, Raymond M
dc.contributor.authorSantibanez-Koref, Mauro F
dc.contributor.authorMargison, Geoffrey P
dc.contributor.authorPovey, Andrew C
dc.date.accessioned2009-03-12T17:14:02Z
dc.date.available2009-03-12T17:14:02Z
dc.date.issued2008-02-15
dc.identifier.citationAssociation between lung cancer risk and single nucleotide polymorphisms in the first intron and codon 178 of the DNA repair gene, O6-alkylguanine-DNA alkyltransferase. 2008, 122 (4):791-5 Int. J. Canceren
dc.identifier.issn1097-0215
dc.identifier.pmid17957803
dc.identifier.doi10.1002/ijc.23059
dc.identifier.urihttp://hdl.handle.net/10541/55036
dc.description.abstractThe association between lung cancer risk and 2 polymorphisms, rs12268840 and rs2308327 (codon K178R), in the DNA repair protein, O(6)-alkylguanine-DNA alkyltransferase, which are associated with interindividual differences in activity, have been investigated in 3 hospital-based case-control studies. Genotyping was carried out on 617 subjects of whom 255 had lung cancer. In 2 of the 3 series, there was a significant inverse association between the 178R allele and case status (p < 0.05). In a meta-analysis, the odds ratio (95% CI) associated with the 178R allele relative to the 178K allele was 0.64 (0.45-0.92, p = 0.01) and 0.51 (0.24-1.11, p = 0.09) in fixed effects and random effects models, respectively. In a pooled analysis, after adjustment for sex, age, pack years and series, the OR (95% CI) for a heterozygote was 0.67 (0.45-1.01) and for a 178R homozygote was 0.10 (0.01-0.94); the trend for a decreased risk with the number of R alleles was significant (p = 0.008). This trend was particularly pronounced in heavy smokers (trend test p = 0.003), but not significant in light smokers (p = 0.73). There was no evidence of an association between rs12268840 and lung cancer risk. These results suggest that the R allele may protect against lung cancer, specifically in heavy smokers, an effect that may result from this polymorphism affecting the function of the MGMT protein and/or levels in MGMT activity.
dc.language.isoenen
dc.subjectLung Canceren
dc.subjectTobacco Smokeen
dc.subjectMGMTen
dc.subjectDNA Repairen
dc.subjectPolymorphismen
dc.subject.meshAdenocarcinoma
dc.subject.meshAged
dc.subject.meshCarcinoma, Small Cell
dc.subject.meshCarcinoma, Squamous Cell
dc.subject.meshCase-Control Studies
dc.subject.meshCodon
dc.subject.meshDNA Repair
dc.subject.meshFemale
dc.subject.meshGenetic Predisposition to Disease
dc.subject.meshGenotype
dc.subject.meshHumans
dc.subject.meshIntrons
dc.subject.meshLung Neoplasms
dc.subject.meshMale
dc.subject.meshMiddle Aged
dc.subject.meshO(6)-Methylguanine-DNA Methyltransferase
dc.subject.meshPolymorphism, Single Nucleotide
dc.subject.meshRisk Factors
dc.subject.meshSmoking
dc.titleAssociation between lung cancer risk and single nucleotide polymorphisms in the first intron and codon 178 of the DNA repair gene, O6-alkylguanine-DNA alkyltransferase.en
dc.typeArticleen
dc.contributor.departmentCancer Research UK Carcinogenesis Group, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, United Kingdom.en
dc.identifier.journalInternational Journal of Canceren
html.description.abstractThe association between lung cancer risk and 2 polymorphisms, rs12268840 and rs2308327 (codon K178R), in the DNA repair protein, O(6)-alkylguanine-DNA alkyltransferase, which are associated with interindividual differences in activity, have been investigated in 3 hospital-based case-control studies. Genotyping was carried out on 617 subjects of whom 255 had lung cancer. In 2 of the 3 series, there was a significant inverse association between the 178R allele and case status (p < 0.05). In a meta-analysis, the odds ratio (95% CI) associated with the 178R allele relative to the 178K allele was 0.64 (0.45-0.92, p = 0.01) and 0.51 (0.24-1.11, p = 0.09) in fixed effects and random effects models, respectively. In a pooled analysis, after adjustment for sex, age, pack years and series, the OR (95% CI) for a heterozygote was 0.67 (0.45-1.01) and for a 178R homozygote was 0.10 (0.01-0.94); the trend for a decreased risk with the number of R alleles was significant (p = 0.008). This trend was particularly pronounced in heavy smokers (trend test p = 0.003), but not significant in light smokers (p = 0.73). There was no evidence of an association between rs12268840 and lung cancer risk. These results suggest that the R allele may protect against lung cancer, specifically in heavy smokers, an effect that may result from this polymorphism affecting the function of the MGMT protein and/or levels in MGMT activity.


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