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

[Open access]Oxidative damage to guanine (8-oxoGua) is one of the most abundant lesions induced by oxidative stress anddocumented 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 steadystate. The aim of this study was to investigate urinary 8-oxoGua as a risk factor for lung cancer. In a nestedcase-cohort design we examined associations between urinary excretion of 8-oxoGua and risk of lung canceras well as potential interaction with the OGG1 Ser326Cys polymorphism in a population-based cohort of25,717 men and 27,972 women aged 50-64 years with 3-7 years follow-up. We included 260 cases with lungcancer and a subcohort of 263 individuals matched on sex, age, and smoking duration for comparison. Urine collectedat entry was analysed for 8-oxoGua by HPLC with electrochemical detection. There was no significant effectof smoking or OGG1 genotype on the excretion of 8-oxoGua. Overall the incidence rate ratio (IRR) (95%confidence interval) of lung cancerwas 1.06 (0.97-1.15) per doubling of 8-oxoGua excretion. The association betweenlung cancer risk and 8-oxoGua excretion was significant among men [IRR: 1.17 (1.03-1.31)], neversmokers[IRR: 9.94 (1.04-94.7)], and former smokers [IRR: 1.19 (1.07-1.33)]. There was no significant interactionwith 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-smokerssuggests that oxidative stress with damage to DNA is important in this group.