Carcinogenesis Advance Access published online on July 29, 2004
Carcinogenesis, doi:10.1093/carcin/bgh240
© 2004 by Oxford University Press
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1 Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, Maryland 20892
* To whom correspondence should be addressed. E-mail: qingl{at}mail.nih.gov.
Lung cancer rates among men and particularly among women, almost all of whom are nonsmokers, in Xuan Wei County, China are among the highest in China and have been causally associated with exposure to indoor smoky coal emissions that contain very high levels of polycyclic aromatic hydrocarbons (PAHs). As such, this population provides a relatively unique opportunity to study the pathogenesis of PAH-induced lung cancer that is not substantially influenced by the large number of other carcinogenic constituents of tobacco smoke. Aldo-keto reductases (AKRs) activate PAH dihydrodiols to yield their corresponding reactive and redox-active o-quinones, which can then generate reactive oxygen species that cause oxidative DNA damage. We therefore examined the association between single nucleotide polymorphisms (SNPs) in four genes (AKR1C3-Gln5His, NQO1-Pro187Ser, MnSOD-Val16Ala, and OGG1-Ser326Cys) that play a role in the generation, prevention or repair of oxidative damage and lung cancer risk in a population-based case-control study of 118 cases and 113 controls in Xuan Wei, China. The AKR1C3 Gln/Gln genotype was associated with a 1.84-fold (95% Confidence Interval [CI] = 0.98-3.45) increased risk and the combined OGG1 Cys/Cys and Ser/Cys genotypes were associated with a 1.93-fold (95% CI = 1.12-3.32) increased risk of lung cancer. Subgroup analysis revealed that the effects were particularly elevated among women who had relatively high cumulative exposure to smoky coal. SNPs in MnSOD and NQ01 were not associated with lung cancer risk. These results suggest that SNPs in the oxidative stress related-genes AKR1C3 and OGG1 may play a role in the pathogenesis of lung cancer in this population, particularly among heavily exposed women. However, due to the small sample size, additional studies are needed to evaluate these associations within Xuan Wei and other populations with substantial exposure to PAHs.
Revised June 21, 2004
Accepted July 18, 2004
MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION
Oxidative damage-related genes AKR1C3 and OGG1 modulate risks for lung cancer due to exposure to PAH-rich coal combustion emissions
2 National Health and Environmental Effects Research Laboratory, United States Environmental Protection Agency, Research Triangle Park, North Carolina 27711
3 Chinese Academy of Preventive Medicine, Beijing, China
4 University of California, Berkeley, California 94720
5 Yale School of Public Health, Yale University, New Haven, Connecticut 06520
6 Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15260
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