Carcinogenesis Advance Access published online on December 19, 2005
Carcinogenesis, doi:10.1093/carcin/bgi313
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Environmental and Occupational Health, University of Copenhagen, Denmark
* To whom correspondence should be addressed. 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 year 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 (8 cases and 8 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.
Received November 21, 2005
Revised December 7, 2005
Accepted December 11, 2005
MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION
Prospective study of 8-oxo-7,8-dihydro-2'-deoxyguanosine excretion and the risk of lung cancer
Steffen Loft 1 *,
Peter Svoboda 2,
Hiroshi Kasai 2,
Anne Tjønneland 3,
Ulla Vogel 4,
Peter Møller 1,
Kim Overvad 5,
and
Ole Raaschou-Nielsen 3
2 Department of Environmental Oncology, Institute of Industrial Ecological Sciences, University of Occupational Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan
3 Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark
4 National Institute of Occupational Health, Copenhagen, Denmark
5 Department of Clinical Epidemiology, Aalborg Hospital, Aarhus University Hospital, Aalborg, Denmark
Steffen Loft, E-mail: s.loft{at}pubhealth.ku.dk
Abstract 
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. S. Cooke, R. Olinski, S. Loft, and members of the European Standards Committee on Uri Measurement and Meaning of Oxidatively Modified DNA Lesions in Urine Cancer Epidemiol. Biomarkers Prev., January 1, 2008; 17(1): 3 - 14. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.-C. Wu, Q. Wang, L.-W. Wang, H.-I Yang, H. Ahsan, W.-Y. Tsai, L.-Y. Wang, S.-Y. Chen, C.-J. Chen, and R. M. Santella Urinary 8-oxodeoxyguanosine, aflatoxin B1 exposure and hepatitis B virus infection and hepatocellular carcinoma in Taiwan Carcinogenesis, May 1, 2007; 28(5): 995 - 999. [Abstract] [Full Text] [PDF]
|
|