The paraoxonase enzyme plays a significant role in the detoxification of various organophosphorous compounds in mammals, and paraoxonase (PON) 1 is one of the endogenous free-radical scavenging systems in the human body. In this study, we investigated the interaction between cigarette smoking and the genetic polymorphism of PON1 with lung cancer in Korean males.

Three hundred thirty five patients with lung cancer and an equal number of age-matched controls were enrolled in this study. Every subject was asked to complete a questionnaire concerning their smoking habits and alcohol drinking habits. A 5' exonuclease assay (TaqMan) was used to genotype the PON1 Q192R polymorphism. The effects of smoking habits and drinking habits, the PON1 Q192R polymorphism and their interactions were statistically analyzed.

Cigarette smoking and the Q/Q genotype of PON1 were significant risk factors for lung cancer. Individuals carrying the Q/Q genotype of PON1 were at a higher risk for lung cancer as compared with those individuals carrying the Q/R or R/R genotype (odds ratio, 2.84; 95% confidence interval, 1.69 - 4.79). When the groups were further stratified by the smoking status, the Q/Q PON1 was associated with lung cancer among the current or ex-smokers (odds ratio, 2.56; 95% confidence interval, 1.52 - 4.31). Current smokers or ex-smokers who had the Q/Q genotype showed an elevated risk for lung cancer (odds ratio: 15.50, 95% confidence interval: 6.76 - 35.54) as compared with the group of subjects who never smoked, and had the Q/R or R/R genotype. The odds ratios (95% confidence interval) of smokers with the PON1 Q/Q type compared to the nonsmokers with the PON1 Q/R or R/R type were 53.77 (6.55 - 441.14) for squamous cell carcinoma, 6.25 (1.38 - 28.32) for adenocarcinoma, and 59.94 (4.66 - 770.39) for small cell carcinoma, and these results were statistically significant.

These results suggest that cigarette smoking and the PON1 Q/Q genotype are risk factors for lung cancer. The combination of cigarette smoking and the PON1 Q/Q genotype significantly increased the lung cancer risk irrespective of the histologic type of cancer.