Carcinogenesis Advance Access originally published online on July 29, 2004
Carcinogenesis 2004 25(11):2177-2181; doi:10.1093/carcin/bgh240
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Carcinogenesis vol.25 no.11 © Oxford University Press 2004; all rights reserved.
ARTICLE |
Oxidative damage-related genes AKR1C3 and OGG1 modulate risks for lung cancer due to exposure to PAH-rich coal combustion emissions
1 Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD 20892, USA, 2 National Health and Environmental Effects Research Laboratory, United States Environmental Protection Agency, Research Triangle Park, NC 27711, USA, 3 Chinese Academy of Preventive Medicine, Beijing, China, 4 University of California, Berkeley, CA 94720, USA, 5 Yale School of Public Health, Yale University, New Haven, CT 06520, USA and 6 Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, PA 15260, USA
7 To whom correspondence should be addressed Email: qingl{at}mail.nih.gov
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.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  C.-H. Chang, C.-F. Hsiao, G.-C. Chang, Y.-H. Tsai, Y.-M. Chen, M.-S. Huang, W.-C. Su, W.-S. Hsieh, P.-C. Yang, C.-J. Chen, et al. Interactive Effect of Cigarette Smoking With Human 8-Oxoguanine DNA N-Glycosylase 1 (hOGG1) Polymorphisms on the Risk of Lung Cancer: A Case-Control Study in Taiwan Am. J. Epidemiol., September 15, 2009; 170(6): 695 - 702. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. J. Davies, R. E. Hayden, P. J. Simpson, J. Birtwistle, K. Mayer, J. P. Ride, and C. M. Bunce AKR1C Isoforms Represent a Novel Cellular Target for Jasmonates alongside Their Mitochondrial-Mediated Effects Cancer Res., June 1, 2009; 69(11): 4769 - 4775. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. D. Figueroa, N. Malats, M. Garcia-Closas, F. X. Real, D. Silverman, M. Kogevinas, S. Chanock, R. Welch, M. Dosemeci, Q. Lan, et al. Bladder cancer risk and genetic variation in AKR1C3 and other metabolizing genes Carcinogenesis, October 1, 2008; 29(10): 1955 - 1962. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.D. Hosgood III, I. Menashe, M. Shen, M. Yeager, J. Yuenger, P. Rajaraman, X. He, N. Chatterjee, N. E. Caporaso, Y. Zhu, et al. Pathway-based evaluation of 380 candidate genes and lung cancer susceptibility suggests the importance of the cell cycle pathway Carcinogenesis, October 1, 2008; 29(10): 1938 - 1943. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Azzarello, K.-M. Fung, and H.-K. Lin Tissue Distribution of Human AKR1C3 and Rat Homolog in the Adult Genitourinary System J. Histochem. Cytochem., September 1, 2008; 56(9): 853 - 861. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Li, X. Hao, W. Zhang, Q. Wei, and K. Chen The hOGG1 Ser326Cys Polymorphism and Lung Cancer Risk: A Meta-analysis Cancer Epidemiol. Biomarkers Prev., July 1, 2008; 17(7): 1739 - 1745. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. S. Bains, R. H. Takahashi, T. A. Pfeifer, T. A. Grigliatti, R. E. Reid, and K. W. Riggs Two Allelic Variants of Aldo-Keto Reductase 1A1 Exhibit Reduced in Vitro Metabolism of Daunorubicin Drug Metab. Dispos., May 1, 2008; 36(5): 904 - 910. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-y. Liu, Y.-H. Hsu, P.-C. Pan, M.-T. Wu, C.-K. Ho, L. Su, X. Xu, Y. Li, D. C. Christiani, and the Kaohsiung Leukemia Research Group Maternal and offspring genetic variants of AKR1C3 and the risk of childhood leukemia Carcinogenesis, May 1, 2008; 29(5): 984 - 990. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Chao, Z.-F. Zhang, J. Berthiller, P. Boffetta, and M. Hashibe NAD(P)H:Quinone Oxidoreductase 1 (NQO1) Pro187Ser Polymorphism and the Risk of Lung, Bladder, and Colorectal Cancers: a Meta-analysis. Cancer Epidemiol. Biomarkers Prev., May 1, 2006; 15(5): 979 - 987. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. W. Hill and M. K. Evans Dimerization and opposite base-dependent catalytic impairment of polymorphic S326C OGG1 glycosylase Nucleic Acids Res., March 20, 2006; 34(5): 1620 - 1632. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. J. Hung, J. Hall, P. Brennan, and P. Boffetta Genetic Polymorphisms in the Base Excision Repair Pathway and Cancer Risk: A HuGE Review Am. J. Epidemiol., November 15, 2005; 162(10): 925 - 942. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Vineis and K. Husgafvel-Pursiainen Air pollution and cancer: biomarker studies in human populations Carcinogenesis, November 1, 2005; 26(11): 1846 - 1855. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. A. Lawson, K. Woodson, J. Virtamo, and D. Albanes Association of the NAD(P)H:Quinone Oxidoreductase (NQO1) 609C->T Polymorphism with Lung Cancer Risk among Male Smokers Cancer Epidemiol. Biomarkers Prev., September 1, 2005; 14(9): 2275 - 2276. [Full Text] [PDF]
|
|