Association between lung cancer risk and single nucleotide polymorphisms in the first intron and codon 178 of the DNA repair gene, O6-alkylguanine-DNA alkyltransferase.

2.50
Hdl Handle:
http://hdl.handle.net/10541/55036
Title:
Association between lung cancer risk and single nucleotide polymorphisms in the first intron and codon 178 of the DNA repair gene, O6-alkylguanine-DNA alkyltransferase.
Authors:
Crosbie, Philip A J; McGown, Gail; Thorncroft, Mary R; O'Donnell, Paul; Barber, Philip V; Lewis, Sarah J; Harrison, Kathryn L; Agius, Raymond M; Santibanez-Koref, Mauro F; Margison, Geoffrey P; Povey, Andrew C
Abstract:
The 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.
Affiliation:
Cancer Research UK Carcinogenesis Group, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, United Kingdom.
Citation:
Association 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. Cancer
Journal:
International Journal of Cancer
Issue Date:
15-Feb-2008
URI:
http://hdl.handle.net/10541/55036
DOI:
10.1002/ijc.23059
PubMed ID:
17957803
Type:
Article
Language:
en
ISSN:
1097-0215
Appears in Collections:
All Paterson Institute for Cancer Research; Carcinogenesis Group

Full metadata record

DC FieldValue Language
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.en
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

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