Journal Article

Prospective study of 8-oxo-7,8-dihydro-2′-deoxyguanosine excretion and the risk of lung cancer

Steffen Loft, Peter Svoboda, Hiroshi Kasai, Anne Tjønneland, Ulla Vogel, Peter Møller, Kim Overvad and Ole Raaschou-Nielsen

in Carcinogenesis

Volume 27, issue 6, pages 1245-1250
Published in print June 2006 | ISSN: 0143-3334
Published online December 2005 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgi313
Prospective study of 8-oxo-7,8-dihydro-2′-deoxyguanosine excretion and the risk of lung cancer

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Oxidative damage to DNA may be important in carcinogenesis and a possible risk factor for lung cancer. The urinary excretion of products of damaged nucleotides in cellular pools or in DNA may be important biomarkers of exposure to relevant carcinogens reflecting the rate of damage in steady state and may predict cancer risk. Oxidation of guanine in DNA or the nucleotide pool may give rise to 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) for urinary excretion. Oxoguanine glycosylase (OGG1) is the base excision enzyme repairing 8-oxodG in DNA by release of 8-oxoguanine. In a nested case–cohort design we examined associations between urinary excretion of 8-oxodG and risk of lung cancer as well as potential interaction with the OGG1 Ser326Cys polymorphism in a population-based cohort of 25 717 men and 27 972 women aged 50–64 years with 3–7 years follow-up. We included 260 cases with lung cancer and a sub-cohort of 263 individuals matched on sex, age and smoking duration for comparison. Urine collected at entry was analysed for 8-oxodG by HPLC with electrochemical detection. The excretion of 8-oxodG was higher in current smokers, whereas OGG1 genotype had no effect. Overall the incidence rate ratio (IRR) (95% confidence interval) of lung cancer was 0.99 (0.80–1.22) per doubling of 8-oxodG excretion and there was no interaction with OGG1 genotype. However, among never-smokers (eight cases and eight sub-cohort members) the IRR was 11.8 (1.21–115) per doubling of 8-oxodG excretion. The association between 8-oxodG excretion and lung cancer risk among never-smokers suggests that oxidative damage to DNA nucleotides is important in this group.

Keywords: IRR, incidence rate ratio; MTH1, MutT homolog; OGG1, oxoguanine glycosylase; PAH, polycyclic aromatic hydrocarbons; ROS, reactive oxygen species; 8-oxodG, 8-oxo-7,8-dihydro-2′-deoxyguanosine

Journal Article.  5015 words. 

Subjects: Clinical Cytogenetics and Molecular Genetics

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