OGG1 expression and OGG1 Ser326Cys polymorphism and risk of lung cancer in a prospective study.

2.50
Hdl Handle:
http://hdl.handle.net/10146/36632
Title:
OGG1 expression and OGG1 Ser326Cys polymorphism and risk of lung cancer in a prospective study.
Authors:
Hatt, Lotte; Loft, Steffen; Risom, Lotte; Moller, Peter; Sorensen, Mette; Raaschou-Nielsen, Ole; Overvad, Kim; Tjonneland, Anne; Vogel, Ulla
Abstract:
Oxidative DNA damage is believed to be implicated in lung carcinogenesis. 8-OxodG is a mutagenic and abundant oxidative modification induced in DNA. OGG1, NEIL1 and MUTYH are all involved in the repair and prevention of 8-oxodG-derived mutations and may be up-regulated by oxidative stress. The polymorphism OGG1 Ser326Cys has in some studies been associated with risk of lung cancer. In a population-based cohort of 57,053 Danes, we examined associations between mRNA levels of OGG1, NEIL1, MUTYH and NUDT in buffy coat material and subsequent lung cancer risk. 260 cases with lung cancer were identified and a sub-cohort of 263 individuals was matched on sex, age and smoking duration. We found that OGG1 mRNA levels in healthy individuals were not associated with risk of subsequent getting lung cancer. However, subjects with the OGG1 Cys326/Cys326 genotype had a higher expression level of OGG1 mRNA than wildtype-allele carriers. For homozygous Cys326 carriers, the incidence rate ratio (IRR) was 1.51 (95% CI: 1.09-2.08) for a doubling of the OGG1 mRNA level and there was a statistically significant interaction between the genotype and mRNA level. Among never-smokers, the IRR was 4.29 (1.09-16.9) per doubling of the OGG1 mRNA level, which was not found among smokers. Furthermore, we found a positive correlation between OGG1 mRNA expression and urinary excretion of 8-oxodG (RS=0.18; p<0.005). NUDT1 mRNA levels were omitted due to low and unreliable expression levels. The results suggest that OGG1 mRNA levels should be regarded as a biomarker of exposure to oxidative stress with induction of DNA rather than a marker of inborn DNA repair capacity.
Citation:
Mutat. Res. 2008, 639 (1-2):45-54
Journal:
Mutation Research
Issue Date:
1-Mar-2008
URI:
http://hdl.handle.net/10146/36632
DOI:
10.1016/j.mrfmmm.2007.11.002
PubMed ID:
18155253
Additional Links:
http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T2C-4R5F1XX-1&_user=1843694&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_version=1&_urlVersion=0&_userid=1843694&md5=5abc6e3cee7d53bb38e5b03fa2370d74
Type:
Article
Language:
en
ISSN:
0027-5107
Sponsors:
This work was supported by the Danish Research Agency (DRAGE Grant 22-02-0356), a Grant from the Danish Ministry of Health, Research Centre, for Environmental Health's Fund, The Danish Cancer Society (Grant DP00027), AIRPOLIFE and ECNIS (Environmental Cancer Risk, Nutrition and Individual Susceptibility), a network of excellence operating within the European Union 6th Framework Program, Priority 5: “Food Quality and Safety” (Contract No. 513943).
Appears in Collections:
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Full metadata record

DC FieldValue Language
dc.contributor.authorHatt, Lotte-
dc.contributor.authorLoft, Steffen-
dc.contributor.authorRisom, Lotte-
dc.contributor.authorMoller, Peter-
dc.contributor.authorSorensen, Mette-
dc.contributor.authorRaaschou-Nielsen, Ole-
dc.contributor.authorOvervad, Kim-
dc.contributor.authorTjonneland, Anne-
dc.contributor.authorVogel, Ulla-
dc.date.accessioned2008-08-27T12:09:48Z-
dc.date.available2008-08-27T12:09:48Z-
dc.date.issued2008-03-01-
dc.identifier.citationMutat. Res. 2008, 639 (1-2):45-54en
dc.identifier.issn0027-5107-
dc.identifier.pmid18155253-
dc.identifier.doi10.1016/j.mrfmmm.2007.11.002-
dc.identifier.urihttp://hdl.handle.net/10146/36632-
dc.description.abstractOxidative DNA damage is believed to be implicated in lung carcinogenesis. 8-OxodG is a mutagenic and abundant oxidative modification induced in DNA. OGG1, NEIL1 and MUTYH are all involved in the repair and prevention of 8-oxodG-derived mutations and may be up-regulated by oxidative stress. The polymorphism OGG1 Ser326Cys has in some studies been associated with risk of lung cancer. In a population-based cohort of 57,053 Danes, we examined associations between mRNA levels of OGG1, NEIL1, MUTYH and NUDT in buffy coat material and subsequent lung cancer risk. 260 cases with lung cancer were identified and a sub-cohort of 263 individuals was matched on sex, age and smoking duration. We found that OGG1 mRNA levels in healthy individuals were not associated with risk of subsequent getting lung cancer. However, subjects with the OGG1 Cys326/Cys326 genotype had a higher expression level of OGG1 mRNA than wildtype-allele carriers. For homozygous Cys326 carriers, the incidence rate ratio (IRR) was 1.51 (95% CI: 1.09-2.08) for a doubling of the OGG1 mRNA level and there was a statistically significant interaction between the genotype and mRNA level. Among never-smokers, the IRR was 4.29 (1.09-16.9) per doubling of the OGG1 mRNA level, which was not found among smokers. Furthermore, we found a positive correlation between OGG1 mRNA expression and urinary excretion of 8-oxodG (RS=0.18; p<0.005). NUDT1 mRNA levels were omitted due to low and unreliable expression levels. The results suggest that OGG1 mRNA levels should be regarded as a biomarker of exposure to oxidative stress with induction of DNA rather than a marker of inborn DNA repair capacity.en
dc.description.sponsorshipThis work was supported by the Danish Research Agency (DRAGE Grant 22-02-0356), a Grant from the Danish Ministry of Health, Research Centre, for Environmental Health's Fund, The Danish Cancer Society (Grant DP00027), AIRPOLIFE and ECNIS (Environmental Cancer Risk, Nutrition and Individual Susceptibility), a network of excellence operating within the European Union 6th Framework Program, Priority 5: “Food Quality and Safety” (Contract No. 513943).en
dc.language.isoenen
dc.relation.urlhttp://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T2C-4R5F1XX-1&_user=1843694&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_version=1&_urlVersion=0&_userid=1843694&md5=5abc6e3cee7d53bb38e5b03fa2370d74en
dc.subjectLung canceren
dc.subjectProspectiveen
dc.subjectBER gene expressionen
dc.subjectbase excision repair gene expressionen
dc.subject8-oxodGen
dc.subject8-oxo-7,8-dihydro-deoxyguanineen
dc.subjectpolymorphismen
dc.subject.meshAmino Acid Substitution-
dc.subject.meshCase-Control Studies-
dc.subject.meshCohort Studies-
dc.subject.meshCysteine-
dc.subject.meshDNA Glycosylases-
dc.subject.meshDNA Repair-
dc.subject.meshFemale-
dc.subject.meshGenetic Markers-
dc.subject.meshHumans-
dc.subject.meshLung Neoplasms-
dc.subject.meshMale-
dc.subject.meshMiddle Aged-
dc.subject.meshOxidative Stress-
dc.subject.meshPolymorphism, Single Nucleotide-
dc.subject.meshProspective Studies-
dc.subject.meshRNA, Messenger-
dc.subject.meshRisk Factors-
dc.subject.meshSerine-
dc.subject.meshSmoking-
dc.titleOGG1 expression and OGG1 Ser326Cys polymorphism and risk of lung cancer in a prospective study.en
dc.typeArticleen
dc.identifier.journalMutation Researchen

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