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


RESULTS
The 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.


CONCLUSIONS
Our 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.
Department of Preventive Medicine and Medical Research Institute, College of Medicine, Chungbuk National University, Cheongju, Korea; Center for Farmers Safety & Health, Chungbuk National University Hospital, Cheongju, Korea.
Sang-Yong
SY
Eom
Department of Preventive Medicine and Medical Research Institute, College of Medicine, Chungbuk National University, Cheongju, Korea; Center for Farmers Safety & Health, Chungbuk National University Hospital, Cheongju, Korea.
Dong-Hyuk
DH
Yim
Asbestos Damage Relief Center, Korea Environment Corporation, Incheon, Korea.
Chul-Ho
CH
Lee
Department of Internal Medicine and Medical Research Institute, College of Medicine, Chungbuk National University, Cheongju, Korea.
Kang-Hyeon
KH
Choe
Department of Internal Medicine and Medical Research Institute, College of Medicine, Chungbuk National University, Cheongju, Korea.
Jin Young
JY
An
Department of Internal Medicine, College of Medicine, Konkuk University, Seoul, Korea.
Kye Young
KY
Lee
Department of Preventive Medicine and Medical Research Institute, College of Medicine, Chungbuk National University, Cheongju, Korea; Center for Farmers Safety & Health, Chungbuk National University Hospital, Cheongju, Korea.
Yong-Dae
YD
Kim
Department of Preventive Medicine and Medical Research Institute, College of Medicine, Chungbuk National University, Cheongju, Korea; Center for Farmers Safety & Health, Chungbuk National University Hospital, Cheongju, Korea.
Heon
H
Kim
D000368:Aged; D043303:Aryldialkylphosphatase / Q000235:genetics*; D003043:Cocarcinogenesis; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D020641:Polymorphism, Single Nucleotide; D056910:Republic of Korea; D012907:Smoking
D043303:Aryldialkylphosphatase; C468406:PON1 protein, human