Association between 8-oxo-7,8-dihydroguanine excretion and risk of lung cancer in a prospective study

Free Radic Biol Med. 2012 Jan 1;52(1):167-72. doi: 10.1016/j.freeradbiomed.2011.10.439. Epub 2011 Oct 20.


Oxidative damage to guanine (8-oxoGua) is one of the most abundant lesions induced by oxidative stress and documented mutagenic. 8-Oxoguanine DNA glycosylase 1 (OGG1) removes 8-oxoGua from DNA by excision. The urinary excretion of 8-oxoGua is a biomarker of exposure, reflecting the rate of damage in the steady state. The aim of this study was to investigate urinary 8-oxoGua as a risk factor for lung cancer. In a nested case-cohort design we examined associations between urinary excretion of 8-oxoGua 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 subcohort of 263 individuals matched on sex, age, and smoking duration for comparison. Urine collected at entry was analysed for 8-oxoGua by HPLC with electrochemical detection. There was no significant effect of smoking or OGG1 genotype on the excretion of 8-oxoGua. Overall the incidence rate ratio (IRR) (95% confidence interval) of lung cancer was 1.06 (0.97-1.15) per doubling of 8-oxoGua excretion. The association between lung cancer risk and 8-oxoGua excretion was significant among men [IRR: 1.17 (1.03-1.31)], never-smokers [IRR: 9.94 (1.04-94.7)], and former smokers [IRR: 1.19 (1.07-1.33)]. There was no significant interaction with the OGG1 genotype, although the IRR was 1.14 (0.98-1.34) among subjects homozygous for Cys326. The association between urinary 8-oxoGua excretion and lung cancer risk among former and never-smokers suggests that oxidative stress with damage to DNA is important in this group.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / enzymology
  • Adenocarcinoma / epidemiology
  • Adenocarcinoma / genetics*
  • Adenocarcinoma / urine*
  • Adenocarcinoma of Lung
  • Case-Control Studies
  • Chromatography, High Pressure Liquid
  • DNA Glycosylases / genetics*
  • DNA Glycosylases / metabolism
  • Denmark / epidemiology
  • Female
  • Follow-Up Studies
  • Genotype
  • Guanine / analogs & derivatives*
  • Guanine / urine
  • Homozygote
  • Humans
  • Incidence
  • Lung Neoplasms / enzymology
  • Lung Neoplasms / epidemiology
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / urine*
  • Male
  • Middle Aged
  • Oxidative Stress
  • Polymorphism, Genetic
  • Population Surveillance*
  • Prospective Studies
  • Risk Factors
  • Smoking / epidemiology
  • Smoking / urine


  • 8-hydroxyguanine
  • Guanine
  • DNA Glycosylases
  • oxoguanine glycosylase 1, human