Interactions between paraoxonase 1 genetic polymorphisms and smoking and their effects on oxidative stress and lung cancer risk in a Korean population.

Sang-Yong Eom,Heon Kim,Chul-Ho Lee,Jin Young An,Yong-Dae Kim,Dong-Hyuk Yim,Kang-Hyeon Choe,Kye Young Lee,Nancy Lan Guo

doi:10.1371/journal.pone.0119100

Abstract

BackgroundFew studies in epidemiology have evaluated the effects of gene-environment interaction on oxidative stress, even though this interaction is an important etiologic factor in lung carcinogenesis. We investigated the effects of the genetic polymorphisms of paraoxonase 1 (PON1), smoking, and the interaction between the two on lung cancer risk and oxidative stress.MethodsThis study’s subjects consisted of 416 newly diagnosed lung cancer patients and an equal number of matched controls. The GoldenGate assay was used for genotypic analyses of the PON1 gene. Urinary 8-hydroxydeoxyguanosine (8-OHdG) and thiobarbituric acid reactive substances levels were measured as indicators of oxidative stress.ResultsThe PON1 rs662 AA genotype showed a significantly lower risk of lung cancer than the GG genotype (OR = 0.60, 95% CI: 0.36–0.99). The protective effect of the PON1 rs662 AA genotype on lung cancer risk was limited to non-smokers. Lung cancer patients who had the rs662 A allele showed a dose-dependent association between smoking status and oxidative stress markers. Among non-smoking lung cancer patients, urinary 8-OHdG levels were significantly lower in individuals with the rs662 GA and AA genotypes than in those with the GG genotype. Furthermore, we found a significant interaction effect between PON1 rs662 and smoking status on urinary 8-OHdG levels in lung cancer patients.ConclusionsOur results suggest that the protective effect of PON1 rs662 SNP against lung carcinogenesis and the induction of oxidative stress might be modulated by the interaction between PON1 genetic polymorphisms and tobacco smoking.

Highlights

Of all types of cancer, lung cancer has the highest incidence and mortality worldwide [1]
The paraoxonase 1 (PON1) rs662 AA genotype showed a significantly lower risk of lung cancer than the GG genotype (OR = 0.60, 95% confidence intervals (95% CI): 0.36–0.99)
The protective effect of the PON1 rs662 AA genotype on lung cancer risk was limited to non-smokers

Summary

Introduction

Of all types of cancer, lung cancer has the highest incidence and mortality worldwide [1]. Tobacco smoking is the most important risk factor for lung cancer, as it is the most likely cause of approximately 90% of lung cancer cases [3,4]. Tobacco smoking is a major determinant of lung cancer, it is not sufficient to cause cancer in the absence of additional factors, such as genetic susceptibility and exposure to other carcinogens (i.e., asbestos, nickel, chromium, arsenic, or radon). Few studies in epidemiology have evaluated the effects of gene-environment interaction on oxidative stress, even though this interaction is an important etiologic factor in lung carcinogenesis. We investigated the effects of the genetic polymorphisms of paraoxonase 1 (PON1), smoking, and the interaction between the two on lung cancer risk and oxidative stress

Methods

Results

Conclusion