title: Association between 8-oxo-7,8-dihydroguanine excretion and risk of lung cancer in a prospective study.
abstract: 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.
authors: Department of Public Health, Section of Environmental Health, University of Copenhagen, Copenhagen, Denmark. stl@sund.ku.dk
authors: Steffen
authors: S
authors: Loft
authors: Peter
authors: P
authors: Svoboda
authors: Kazuaki
authors: K
authors: Kawai
authors: Hiroshi
authors: H
authors: Kasai
authors: Mette
authors: M
authors: Sørensen
authors: Anne
authors: A
authors: Tjønneland
authors: Ulla
authors: U
authors: Vogel
authors: Peter
authors: P
authors: Møller
authors: Kim
authors: K
authors: Overvad
authors: Ole
authors: O
authors: Raaschou-Nielsen
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics* / Q000652:urine*; D000077192:Adenocarcinoma of Lung; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid; D045647:DNA Glycosylases / Q000235:genetics* / Q000378:metabolism; D003718:Denmark / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006147:Guanine / Q000031:analogs & derivatives* / Q000652:urine; D006720:Homozygote; D006801:Humans; D015994:Incidence; D008175:Lung Neoplasms / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics* / Q000652:urine*; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D011110:Polymorphism, Genetic; D011159:Population Surveillance; D011446:Prospective Studies; D012307:Risk Factors; D012907:Smoking / Q000453:epidemiology / Q000652:urine
chemical_list: C024829:8-hydroxyguanine; D006147:Guanine; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human