• Asian Pacific Journal of Cancer Prevention
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• v.16 no.2
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• pp.803-809
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• 2015

Background: Colorectal cancer (CRC) is a leading cause of cancer-related death. Oxidative DNA damage may contribute to cancer risk and the antioxidant paraoxonase is one endogenous free radical scavenger in the human body which could therefore exert an influeence. Purpose: Aim of this study was to determine the role of serum arylesterase (ARE) and paraoxonase 1(PON1) activities in CRC patients and to find any association between (PON1) Q192R and L55M gene polymorphisms in CRC patients. Also the serum ARE and PON1 activities in CRC patients will be investigated before and after surgery Materials and Methods: This study involved a total of 50 patients with newly diagnosed CRC and 80 healthy controls. PON1 and ARE activities were determined using an enzymatic spectrophotometric method. PON1 Q192R and L55M gene polymorphisms were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) based restriction fragment analysis. The restriction enzyme AlwI was used to examine the Q192R polymorphism and Hsp92II for the L55M polymorphism. Results: Significant differences in the PON1 Q192R polymorphism were found between patients and controls. The Q allele was more frequent in the patient group than in controls, while the R allele was more frequent in the controls. Significant differences were found in the L55M polymorphism. Additionally, there were significant differences in L and M allele frequencies (p=0.001). The serum activities of PON1 and ARE were low in QQ and MM genotype. Conclusions: serum PON1 and ARE activities were significantly lower in CRC patients compared to healthy subjects. The R allele may protect against colorectal cancer.

• Environmental Mutagens and Carcinogens
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• v.21 no.1
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• pp.9-13
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• 2001

Essential hypertension is considered to be a multifactorial disease that is influenced not only by environmental factors but also by genetic factors. Genes involved in lipoprotein synthesis, modification and metabolism are candidates for essential hypertension. The purpose of this study was to estimate gene frequencies of paraoxonase/arylesterase (PON1) gene in Korean population and investigate the relationship between genotypes of this gene and essential hypertension or cardiovascular risk factors. In order to estimate the genotype frequencies, Alw I RFLP of PON1 gene was used as genetic marker. There were no significant differences in allele and genotype frequencies between normotensives and essential hypertensives, respectively. However, Alw I RELP of PON1 gene were significantly associated with plasma HDL-cholesterol level in Korean population (one-way ANOVA test, p=0.008). Therefore, our result suggest that this RFLP of PON1 gene may be protective marker on cardiovascular disease in Korean population.

• Journal of Preventive Medicine and Public Health
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• v.38 no.3
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• pp.345-350
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• 2005

Objectives : Polycyclic aromatic hydrocarbons (PAHs), which are risk factors for lung cancer, have been reported to induce oxidative DNA damage. The paraoxonase (PON) plays a significant role in the detoxification of a variety of organophosphorous compounds, with paraoxonase-1 (PON1) being one of the endogenous free-radical scavenging systems in the human body. The aim of this case-control study was to investigate the effects of PAH exposure, oxidative stress and the Q192R polymorphism of PON1 genes, and their interactions in the carcinogenesis of lung cancer. Methods : One hundred and seventy seven lung cancer patients and 177 age- and sex-matched controls were enrolled in this study. Each subject was asked to complete a questionnaire concerning their smoking habits and environmental exposure to PAHs. The Q192R genotypes of the PON1 gene was examined, and the concentrations of urinary 1-hydroxypyrene (1-OHP), 2-naphthol and 8-hydroxydeoxyguanosine (8-OH-dG) measured. Results : Cigarette smoking was found to be a significant risk factor for lung cancer. The urinary 8-OH-dG level was higher in the patients, whereas the urinary 1-OHP and 2-naphthol levels were higher in the controls. There was a significant correlation between the urinary levels of 8-OHdG and 1-OHP in both the cases and controls. The PON1 polymorphism was associated with an increased risk of lung cancer. Individuals carrying the Q/Q genotype of the PON1 gene were found to be at higher risk of developing lung cancer. There was a significant correlation between the urinary levels of 8-OH-dG and 1-OHP in those with the PON1 Q/Q genotype. Conclusions : These results lead to the conclusion that PAHs would induce oxidative DNA damage, especially in individuals with the PON1 Q/Q genotype. Therefore, people with the PON1 Q/Q genotype would be more susceptible to lung cancer than those with the R/R or Q/R genotypes of the PON1 gene.

• Asian-Australasian Journal of Animal Sciences
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• v.21 no.8
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• pp.1097-1102
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• 2008

Paraoxonase-1 (PON1), like lipoprotein lipase (LPL), plays a key role in the metabolism and physiology of mammalian growth. The objectives of this study were to estimate the allele and genotype frequencies at the PON1/EcoRV and PON1/AluI loci in three genetic groups of beef cattle and to determine associations between these polymorphisms and growth and carcass traits. Genotyping was performed on 30 Angus, 32 Hereford and 26 Simmental. The association analysis was carried out using the GLM procedure of SAS 9.1 and the least squares means of the genotypes were compared by the Tukey's test. Animals with AG genotype at the PON1/EcoRV locus had higher weight at the time of entry into the fattening corrals ($329.97{\pm}6.08kg$) and close to the time of slaughter ($577.56{\pm}8.32kg$) and net meat weight ($275.89{\pm}4.05kg$) and fitted tenderness ($3.10{\pm}0.19kg$) (p<0.05). Animals with AA genotype at the PON1/AluI locus had higher weight at the time of entry ($333.37{\pm}8.93kg$) and slaughter ($576.82{\pm}13.18kg$) and net meat weight ($275.49{\pm}6.43kg$) and average daily gain ($0.68{\pm}0.02kg/d$) (p<0.05). The meat color score was also significantly higher (p<0.05). Between genotypes and breeds, there were significant differences observed except for TBW, REMG, MBS, REA and MCS. As a metabolism gene, genotypes of the SNPs of PON1 gene might be reflecting BFT directly, such as $A_eA_eG_aG_a$ genotype in this experiment.

• Tuberculosis and Respiratory Diseases
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• v.58 no.5
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• pp.490-497
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• 2005

Background : 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. Methods : 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. Results : 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. Conclusion : 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.

• The Journal of Internal Korean Medicine
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• v.31 no.4
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• pp.752-762
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• 2010

Objective : In the present study, we investigated genetic distribution of eight single nucleotide polymorphisms of PON1 between Dampness and Phlegm and non Dampness and Phlegm pattern identification(PI) among Korean stroke patients. Materials and Methods : One hundred forty stroke subject without Dampness and Phlegm and fifty eight stroke subjects with Dampness and Phlegm were participated in this study. After informed consents, eight single nucleotide polymorphisms(SNPs) in PON1 of each subjects were identified by DNA sequencing and primer extension method and statistical analysis was performed to determine the significant difference between Dampness and Phlegm and non Dampness and Phlegm groups. Results : Among anthropometric characteristics and blood parameters, waist circumference and total cholesterol were significantly higher in Dampness and Phlegm. Among 8 SNPs of PON1, frequency of M allele and subjects with M allele in L55M SNP were significantly higher in Dampness and Phlegm group (p=0.0032 and p=0.0053, respectively) but subjects with T allele in C-2033T SNP were lower in Dampness and Phlegm group(p=0.0302). Effect of L55M and C-2033T on Dampness and Phlegm were 3.07% and 1.75%, respectively. Conclusion : Our results suggest that L55M SNP in exon and C-2033T in promoter region of PON1 maybe affect to Dampness and Phlegm pattern identification. However, further study should be carried out to find out the detailed mechanism how L55M and C-2033T can affect Dampness and Phlegm stroke patients.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.10
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• pp.4457-4463
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• 2015

Common genetic variation Q192R in the paraoxonase 1 (PON1) gene has been considered to be implicated in the development of many cancers. Nevertheless, results from the related studies were inconsistent. To elucidate the association, we performed a meta-analysis for 8,112 cases and 10,037 controls from 32 published case-control studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the association by STATA 12.0 software. Overall, we revealed that the PON1-192R allele was associated with a reduced risk of the overall cancers. Moreover, in the stratified analysis by cancer types (breast cancer, prostate cancer, brain cancer etc.), the results showed that PON1-192R allele was associated with a decreased risk in breast cancer (R vs Q: OR=0.605, 95% CI=0.378-0.967, $P_{heterogeneity}=0.000$; RR vs QQ: OR=0.494, 95% CI=0.275-0.888, $P_{heterogeneity}=0.002$; RQ vs QQ: OR=0.465, 95% CI=0.259-0.835, $P_{heterogeneity}=0.000$; and RR+RQ vs QQ: OR=0.485, 95% CI=0.274-0.857, $P_{heterogeneity}=0.000$), and associated with prostate cancer in homozygote (RR vs QQ: OR=0.475, 95% CI=0.251-0.897, $P_{heterogeneity}=0.001$) and recessive models (RR vs RQ+QQ: OR=0.379, 95% CI=0.169-0.853, $P_{heterogeneity}=0.000$), while an increased risk was identified in lymphoma (R vs Q: OR=1.537, 95% CI=1.246-1.896, $P_{heterogeneity}=0.944$; RR vs QQ: OR=2.987, 95% CI=1.861-4.795, $P_{heterogeneity}=0.350$; RR+RQ vs QQ: OR=1.354, 95% CI=1.021-1.796, $P_{heterogeneity}=0.824$; and RR vs RQ+QQ: OR=2.934, 95% CI=1.869-4.605, $P_{heterogeneity}=0.433$), and an increased risk in prostate cancer under heterozygote comparison (RQ vs QQ: OR=1.782, 95% CI=1.077-2.950, $P_{heterogeneity}=0.000$) and dominant models (RR+RQ vs QQ: OR=1.281, 95% CI=1.044-1.573, $P_{heterogeneity}=0.056$). When subgroup analysis that performed by the control source (hospital based or population based), a decreased risk of the overall cancers was revealed by homozygote (RR vs QQ: OR=0.601, 95% CI=0.366-0.987, $P_{heterogeneity}=0.000$) and dominant models (RR vs RQ+QQ: OR= 0.611, 95% CI=0.384-0.973, $P_{heterogeneity}=0.000$) in hospital based group. Stratifying by ethnicity, a significantly reduced risk of the overall cancers under allele contrast model (R vs Q: OR=0.788, 95% CI=0.626-0.993, $P_{heterogeneity}=0.000$) was uncovered in Caucasian. In summary, these findings suggested that PON1 Q192R polymorphism was associated with a reduced risk of the overall cancers, nevertheless, it might increase cancer susceptibility of prostate and lymphoma risk. Large well-designed epidemiological studies will be continued on this issue of interest.