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

Abstract

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.

NAD(P)H:Quinone Oxidoreductase 1 (NQO1) Pro187Ser Polymorphism and the Risk of Lung, Bladder, and Colorectal Cancers: a Meta-analysis

“…Twenty-one case-control studies examining the effect of NQO1 Pro187Ser polymorphisms on the risk of lung cancer were identified (16,(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45); one study was only identified from citation (34), and one was an unpublished study (44). We excluded one study due to the lack of genotype information (37).…”

Lack of Association between the hOGG1 Ser326Cys Polymorphism and Gastric Cancer Risk: a Meta-analysis

“…Studies indicated a role of the HOGG1 Ser326Cys polymorphism in many cancers including oro-laryngeal cancer (Elahi et al, 2002;Yang et al, 2008), esophageal cancer (Xing et al, 2001), lung cancer (Lan et al, 2004), gastric cancer (Hanaoka et al, 2001), renal cell carcinoma (RCC) (Zhao et al, 2011), gallbladder cancer (Jiao et al, 2007), bladder cancer (Arizono et al, 2008), prostate cancer (Zhang et al, 2010) and acute lymphoblastic leukemia (Stanczyk et al, 2011).…”

Triphlorethol-A Improves the Non-Homologous End Joining and Base-Excision Repair Capacity Impaired by Formaldehyde

“…The BER enzyme 8-oxoguanine glycosylase (OGG1) repairs 8-OhdG in mammals, and thus preserves genomic integrity and genetic functions. Lan et al (2004) suggested that OGG1 deficiency was associated with an increase in mutations and may participate in carcinogenesis.…”