Journal Article

Oxidative damage-related genes <i>AKR1C3</i> and <i>OGG1</i> modulate risks for lung cancer due to exposure to PAH-rich coal combustion emissions

Qing Lan, Judy L. Mumford, Min Shen, David M. DeMarini, Matthew R. Bonner, Xingzhou He, Meredith Yeager, Robert Welch, Stephen Chanock, Linwei Tian, Robert S. Chapman, Tongzhang Zheng, Phouthone Keohavong, Neil Caporaso and Nathaniel Rothman

in Carcinogenesis

Volume 25, issue 11, pages 2177-2181
Published in print November 2004 | ISSN: 0143-3334
Published online November 2004 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgh240
Oxidative damage-related genes AKR1C3 and OGG1 modulate risks for lung cancer due to exposure to PAH-rich coal combustion emissions

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Lung cancer rates among men and particularly among women, almost all of whom are non-smokers, 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 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 119 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 = 1.12–3.34) 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 NQO1 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.

Keywords: AKR, aldo-keto reductases; PAH, polycyclic aromatic hydrocarbons; ROS, reactive oxygen species; SNP, single nucleotide polymorphisms

Journal Article.  3892 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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