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

Lotte Hatt; Steffen Loft; Lotte Risom; Peter Møller; Mette Sørensen; Ole Raaschou-Nielsen; Kim Overvad; Anne Tjønneland; Ulla Vogel

doi:10.1016/j.mrfmmm.2007.11.002

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

Lotte Hatt, Steffen Loft, Lotte Risom, Peter Møller, Mette Sørensen, Ole Raaschou-Nielsen, Kim Overvad, Anne Tjønneland, Ulla Vogel

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

54 Citationer (Scopus)

Abstract

Udgivelsesdato: 2008-Mar-1

Originalsprog	Engelsk
Tidsskrift	Mutation Research - Reviews
Vol/bind	639
Udgave nummer	1-2
Sider (fra-til)	45-54
Antal sider	9
ISSN	1383-5742
DOI	https://doi.org/10.1016/j.mrfmmm.2007.11.002
Status	Udgivet - 2008

Bibliografisk note

Keywords: Amino Acid Substitution; Case-Control Studies; Cohort Studies; Cysteine; DNA Glycosylases; DNA Repair; Female; Genetic Markers; Humans; Lung Neoplasms; Male; Middle Aged; Oxidative Stress; Polymorphism, Single Nucleotide; Prospective Studies; RNA, Messenger; Risk Factors; Serine; Smoking

Adgang til dokumentet

10.1016/j.mrfmmm.2007.11.002

Citationsformater

@article{ec4b1e20e93411ddbf70000ea68e967b,

title = "OGG1 expression and OGG1 Ser326Cys polymorphism and risk of lung cancer in a prospective study",

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.",

author = "Lotte Hatt and Steffen Loft and Lotte Risom and Peter M{\o}ller and Mette S{\o}rensen and Ole Raaschou-Nielsen and Kim Overvad and Anne Tj{\o}nneland and Ulla Vogel",

note = "Keywords: Amino Acid Substitution; Case-Control Studies; Cohort Studies; Cysteine; DNA Glycosylases; DNA Repair; Female; Genetic Markers; Humans; Lung Neoplasms; Male; Middle Aged; Oxidative Stress; Polymorphism, Single Nucleotide; Prospective Studies; RNA, Messenger; Risk Factors; Serine; Smoking",

year = "2008",

doi = "10.1016/j.mrfmmm.2007.11.002",

language = "English",

volume = "639",

pages = "45--54",

journal = "Mutation Research - Reviews",

issn = "1383-5742",

publisher = "Elsevier",

number = "1-2",

}

TY - JOUR

T1 - OGG1 expression and OGG1 Ser326Cys polymorphism and risk of lung cancer in a prospective study

AU - Hatt, Lotte

AU - Loft, Steffen

AU - Risom, Lotte

AU - Møller, Peter

AU - Sørensen, Mette

AU - Raaschou-Nielsen, Ole

AU - Overvad, Kim

AU - Tjønneland, Anne

AU - Vogel, Ulla

N1 - Keywords: Amino Acid Substitution; Case-Control Studies; Cohort Studies; Cysteine; DNA Glycosylases; DNA Repair; Female; Genetic Markers; Humans; Lung Neoplasms; Male; Middle Aged; Oxidative Stress; Polymorphism, Single Nucleotide; Prospective Studies; RNA, Messenger; Risk Factors; Serine; Smoking

PY - 2008

Y1 - 2008

N2 - 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.

AB - 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.

U2 - 10.1016/j.mrfmmm.2007.11.002

DO - 10.1016/j.mrfmmm.2007.11.002

M3 - Journal article

C2 - 18155253

SN - 1383-5742

VL - 639

SP - 45

EP - 54

JO - Mutation Research - Reviews

JF - Mutation Research - Reviews

IS - 1-2

ER -