Association Between Multiple Heavy Metal Exposures and Cholesterol Levels in Residents Living Near a Smelter Plant in Korea.

BACKGROUND: Considering the interactions between heavy metals, a comprehensive evaluation of the effects of exposure to various types of co-interacting heavy metals on health is required. This study assessed the association between dyslipidemia markers and blood mercury, lead, cadmium, iron, zinc, and nickel levels in residents of an abandoned refinery plant. METHODS: A total of 972 individuals (exposed group: 567, control group: 405) living near the Janghang refinery plant in the Republic of Korea were included. Blood mercury, lead, cadmium, iron, zinc, nickel, cholesterol, and triglyceride levels were measured. The combined effect of the six heavy metals on dyslipidemia markers was evaluated using a Bayesian kernel machine regression (BKMR) model and compared with the results of a linear regression analysis. The BKMR model results were compared using a stratified analysis of the exposed and control groups. RESULTS: In the BKMR model, the combined effect of the six heavy metals was significantly associated with total cholesterol (TC) levels both below the 45th percentile and above the 55th percentile in the total population. The combined effect range between the 25th and 75th percentiles of the six metals on TC levels was larger in the exposed group than that in the total population. In the control group, the combined effects of the changes in concentration of the six heavy metals on the TC concentration were not statistically significant. CONCLUSION: These results suggest that the cholesterol levels of residents around the Janghang refinery plant may be elevated owing to exposure to multiple heavy metals.

Copper-zinc imbalance induces kidney tubule damage and oxidative stress in a population exposed to chronic environmental cadmium.

PURPOSE: This cross-sectional study aimed to assess the effect of environmental cadmium (Cd) exposure and essential metal imbalance on renal tubular damage and oxidative stress in 979 adults living in a Cd-polluted area near an abandoned copper (Cu) refinery. METHODS: We analyzed urinary Cd concentrations, renal tubular damage and oxidative stress markers, such as beta-2 microglobulin (ß2-MG) and N-acetyl-ß-D-glucosaminidase (NAG) activity and urine malondialdehyde (MDA) levels. The serum copper-to-zinc ratio (CZR) was used as an essential metal imbalance indicator. We divided the subjects into two Cd exposure groups based on the reference level of urinary Cd for renal dysfunction (2 µg/g creatinine). RESULTS: The geometric mean concentration of urinary Cd in all subjects was 2.25 µg/g creatinine. In both low and high Cd exposure groups, urinary Cd levels were positively correlated with urinary NAG activity, but not with serum CZR. After multivariate adjustment, serum CZR was strongly associated with urinary ß2-MG levels in the low Cd exposure group (ß = 1.360, P = 0.019) and was significantly associated with urinary MDA levels, regardless of Cd exposure level. In addition, the risk of renal tubular damage was significantly associated with urinary Cd level, particularly in the lowest or highest CZR tertile groups. CONCLUSIONS: Essential metal imbalance may be a determinant of oxidative stress and renal tubular damage in a chronically Cd-exposed population, and proper zinc supplementation will be effective in preventing adverse health effects due to Cd exposure.

Environmental Exposure to Arsenic, Lead, and Cadmium in People Living near Janghang Copper Smelter in Korea.

Concentrations of heavy metals exceed safety thresholds in the soil near Janghang Copper Refinery, a smelter in Korea that operated from 1936 to 1989. This study was conducted to evaluate the level of exposure to toxic metals and the potential effect on health in people living near the smelter. The study included 572 adults living within 4 km of the smelter and compared them with 413 controls group of people living similar lifestyles in a rural area approximately 15 km from the smelter. Urinary arsenic (As) level did not decrease according to the distance from the smelter, regardless of gender and working history in smelters and mines. However, in subjects who had no occupational exposure to toxic metals, blood lead (Pb) and cadmium (Cd) and urinary Cd decreased according to the distance from the smelter, both in men and women. Additionally, the distance from the smelter was a determinant factor for a decrease of As, Pb, and Cd in multiple regression models, respectively. On the other hands, urinary Cd was a risk factor for renal tubular dysfunction in populations living near the smelter. These results suggest that Janghang copper smelter was a main contamination source of As, Pb, and Cd, and populations living near the smelter suffered some adverse health effects as a consequence. The local population should be advised to make efforts to reduce exposure to environmental contaminants, in order to minimize potential health effects, and to pay close attention to any health problems possibly related to toxic metal exposure.

Dietary aflatoxin B1 intake, genetic polymorphisms of CYP1A2, CYP2E1, EPHX1, GSTM1, and GSTT1, and gastric cancer risk in Korean.

PURPOSE: We investigated the effects of aflatoxin B1 (AFB1) intake, genetic polymorphisms of AFB1 metabolic enzymes, and interactions between the polymorphisms and intake of AFB1 with regard to the risk of gastric cancer in Korean. METHODS: The participants in the study included 477 gastric cancer patients and 477 age- and sex-matched control subjects. Direct interviews and a structured questionnaire were used to determine the level of exposure to AFB1, and the GoldenGate assay and multiplex polymerase chain reaction were used for genotypic analyses of the cytochrome P450 1A2 (CYP1A2), cytochrome P450 1E1, epoxide hydrolase 1, and glutathione S-transferase genes. RESULTS: The probable daily intake of AFB1 was significantly higher among gastric cancer patients than among control subjects (cases vs. controls: 1.91 ± 0.87 vs. 1.65 ± 0.72 ng/kg bw/day, p < 0.0001), and increased AFB1 intake was significantly associated with an elevated risk of gastric cancer (odds ratio 1.94; 95 % confidence interval 1.43-2.63). However, genetic polymorphisms of AFB1 metabolic enzymes were not associated with gastric cancer, with the exception of CYP1A2. Moreover, there was no interaction between AFB1 intake and the genotypes of metabolic enzymes that affect gastric cancer risk. CONCLUSIONS: Our results suggest that dietary AFB1 exposure might be associated with a risk of gastric cancer. However, the effect of AFB1 on gastric carcinogenesis may not be modulated by genetic polymorphisms of AFB1 metabolic enzymes.

Impact of Clinical Association Between Gout and Dementia: A Nationwide Population-Based Cohort Study in Korea.

OBJECTIVE: Hyperuricemia might have neuroprotective or neurodegenerative effects on dementia via oxidative stress or inflammatory response regulation. Few studies have explored the association of hyperuricemia or gout with dementia. This retrospective cohort study aimed to investigate the association between gout and dementia in Korea. METHODS: Altogether, 5,052 gout patients and 25,260 age- and sex-matched controls were selected from the National Health Insurance Service (NHIS)-National Sample Cohort database. The incidence and risk of dementia were evaluated by reviewing the NHIS record. We also performed a subgroup analysis according to age group (age <65 or ≥65 years) using the standard age of 65 years for elderly and nonelderly groups and sex. RESULTS: During follow-up, 81 and 558 participants in the gout and control cohorts developed dementia, respectively. The mean follow-up duration was 4.38 years in gout patients and 4.94 years in controls. Gout patients had a hazard ratio (HR) of 0.79 for overall dementia (95% confidence interval [95% CI] 0.62-1.00) and significantly lower Alzheimer's disease risk (HR 0.73 [95% CI 0.54-0.98]) after adjusting for age, sex, household income, and comorbidities. In subgroup analysis stratified by age and sex, the inverse association between gout and the risk of overall dementia (HR 0.71 [95% CI 0.52-0.97]) and Alzheimer's disease (HR 0.67 [95% CI 0.46-0.97]) were observed in the elderly male group. On the other hand, age- and sex-adjusted analysis showed that the HR for vascular dementia of gout patients was 2.31 (95% CI 1.02-5.25) in the nonelderly male group. CONCLUSION: Gout decreased the risk of incident Alzheimer's disease-type dementia, especially in elderly patients. The association between gout and dementia risk may differ according to age and disease duration.

Association between dementia and systemic rheumatic disease: A nationwide population-based study.

OBJECTIVES: Systemic rheumatic disease is characterized by autoimmunity and systemic inflammation and affects multiple organs. Few studies have investigated whether autoimmune diseases increase the risk of dementia. Herein, we evaluate the relationship between systemic rheumatic disease and dementia through a population-based study using the Korean National Health Insurance Service (NHIS) claims database. METHODS: We conducted a nationwide population-based study using the Korean NHIS database, consisting of individuals who submitted medical claims from 2002-2013. Dementia was defined as having an acetylcholinesterase inhibitors (AChEIs) prescription along with symptoms satisfying the Alzhemier's disease (AD) International Classification of Diseases (ICD)-10 codes (F00 or G30), or vascular dementia (VaD; ICD-10 or F01) criteria. Control subjects were matched to the dementia patients by age and sex. The study group was limited to those diagnosed with rheumatic disease at least 6 months prior to diagnosis of dementia. Rheumatic disease was defined by the following ICD-10 codes: Rheumatoid arthritis (RA: M05), Sjögren's syndrome (SS: M35), systemic lupus erythematosus (SLE: M32), and Behcet's disease (BD: M35.2). RESULTS: Of the 6,028 dementia patients, 261 (4.3%) had RA, 108 (1.6%) had SS, 12 (0.2%) had SLE, and 6 (0.1%) had BD. SLE history was significantly higher in dementia patients (0.2%) than in controls (0.1%) and was associated with dementia (odds ratio [OR], 2.48; 95% confidence interval [CI], 1.19-5.15). In subgroup analysis, SLE significantly increased dementia risk, regardless of dementia type (AD: OR, 2.29; 95% CI, 1.06-4.91; VaD: OR, 4.54; 95% CI, 1.36-15.14). However, these associations were not sustained in the mild CCI or elderly group. CONCLUSION: SLE was independently associated with a higher risk of dementia, including AD and VaD when compared to the control group, even after adjustment. SLE patients (<65 years old) are a high-risk group for early vascular dementia and require screening for early detection and active prevention.

Dietary vitamin D intake and vitamin D related genetic polymorphisms are not associated with gastric cancer in a hospital-based case-control study in Korea.

There have been few studies on the association between vitamin D levels and gastric cancer in Asian populations, but no studies have been performed on the interactions between vitamin D intake and polymorphisms in the vitamin D pathway. The effects of vitamin D intake, vitamin D related genetic polymorphisms, and their association with the incidence of gastric cancer were investigated in a hospital case-control study, including 715 pairs of newly diagnosed gastric cancer patients and controls matched for age and sex. Correlations between vitamin D intake and plasma vitamin D concentrations were also assessed in a subset of subjects. No statistically significant difference was observed in the dietary intake of vitamin D between the patients and controls, nor were there any evident associations between vitamin D intake and risk of gastric cancer in multivariate analyses. Vitamin D intake significantly correlated with the circulating 25-hydroxyvitamin D levels, but not with the active form of the vitamin, 1,25-dihydroxyvitamin D. There were no statistically significant interactions between vitamin D intake, and VDR or TXNIP polymorphisms. This study suggests that dietary vitamin D intake is not associated with gastric cancer risk, and the genetic polymorphisms of vitamin D-related genes do not modulate the effect of vitamin D with respect to gastric carcinogenesis.

The effect of sunblock against oxidative stress in farmers: a pilot study.

Farmers are frequently exposed to ultraviolet (UV) radiation which causes various diseases by inducing oxidative stress. This study aimed to assess the effects of sunblock on oxidative stress in the body. Eighty-seven farmers were divided into two groups: those who wore sunblock for five days and those who did not. The total antioxidant capacity (TAC) in urine, which is an antioxidant indicator, and 8-hydroxy-2-deoxyguanosine (8-OHdG) levels in urine, an oxidative stress indicator, were measured. The urinary TAC of sunblock users was significantly higher than that of non-users, but urinary 8-OHdG levels were not significantly different. Even after adjustment for potential confounders, urinary TAC was found to be markedly increased with sunblock usage. These results suggest that sunblock is effective in preventing oxidative stress among farmers. In addition, they show that urinary TAC can be used as a good effect marker of oxidative stress caused by UV exposure.

A pilot exome-wide association study of age-related cataract in Koreans.

Age-related cataract (ARC) is the most common cause of visual impairment and blindness worldwide. A previous study reported that genetic factors could explain approximately 50% of the heritability of cataract. However, a genetic predisposition to ARC and the contributing factors have not yet been elucidated in the Korean population. In this study, we assessed the influence of genetic polymorphisms on the risk of ARC in Koreans, including 156 cataract cases and 138 healthy adults. We conducted an exome-wide association study using Illumina Human Exome-12v1.2 platform to screen 244,770 single nucleotide polymorphisms (SNPs). No SNPs reached exome-wide significance level of association (P < 1×10(-6)). B3GNT4 rs7136356 showed the most significant association with ARC (P = 6.54×10(-5)). Two loci (MUC16 and P2RY2) among the top 20 ARC-associated SNPs were recognized as probably linked to cataractogenesis. Functions of these genes were potentially related to regulating dehydration or homeostasis of the eyes, and showed a potential association with dry eye disease. This finding suggests that mucin- and dry eye disease-related genes may play a significant role in cataractogenesis. Our study provides insight into the genetic predisposition of ARC in Koreans. Additional studies with larger sample sizes are required to confirm the results of this study.

Additive interactions between PRKAA1 polymorphisms and Helicobacter pylori CagA infection associated with gastric cancer risk in Koreans.

Although several studies reported genetic polymorphisms in protein kinase AMP-activated alpha 1 catalytic subunit (PRKAA1) and their associations with gastric cancer risk, few have evaluated associations between Helicobacter pylori infection and PRKAA1 gene-environment interactions. Here, we evaluated the effects of interactions between H. pylori infection and PRKAA1 polymorphisms on gastric cancer risk in Koreans. In this hospital-based case-control study, PRKAA1 genotypes were analyzed and H. pylori infection and CagA status were examined using a serologic method in 846 pairs of gastric cancer patients and controls matched for age and sex. H. pylori seropositivity was associated with a 1.43-fold [95% confidence interval: 1.12-1.81] increase in the risk of gastric cancer, and CagA low-positive titers during H. pylori infection increased the risk by 1.85-fold (95% confidence interval, 1.38-2.48). Significant positive interaction between the PRKAA1 rs13361707 genotype and H. pylori infection was verified on an additive scale [relative excess risk due to interaction, 0.55; 95% confidence interval, 0.05-1.04; P = 0.030], and the gene-environment interaction between PRKAA1 rs13361707 and CagA status was also statistically significant (relative excess risk due to interaction, 0.50; 95% confidence interval, 0.30-0.70; P < 0.001). Our results indicated that H. pylori infection, CagA status, and PRKAA1 polymorphisms were risk factors for gastric cancer in Koreans, and that the combination of two of these factors rather than their independent effects synergistically increased the risk.

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.

Temporal changes in urinary levels of cadmium, N-acetyl-ß-d-glucosaminidase and ß2-microglobulin in individuals in a cadmium-contaminated area.

Cadmium (Cd) is a metal that is toxic to renal tubules. If renal tubules are damaged by Cd, urinary excretion of N-acetyl-ß-D-glucosaminidase (NAG) and beta 2-microglobulin (ß2-MG) increases. The aim of this study was to describe the changing patterns of urinary Cd, NAG, and ß2-MG levels over a 3-year period in individuals living in a Cd-contaminated area. This follow-up study included 191 residents (65.6±9.3 years) who were living in the vicinity of a copper refinery. Urinary levels of Cd, NAG activity, and ß2-MG levels were measured, and their determinants and changing patterns were analyzed statistically. The natural logarithm of urinary Cd levels decreased significantly over time. Sex and intake of locally cultivated rice were significant determinants of urinary Cd concentration. Urinary NAG activity decreased over time. Age and urinary Cd concentration were significant determinants of urinary NAG activity in subjects with urinary Cd concentrations >5µg/g creatinine. In subjects whose urinary Cd concentrations were >2µg/g creatinine, diabetes was found to be a significant risk factor for high urinary NAG activity. The slope for temporal changes in urinary ß2-MG levels was negative in subjects whose urinary Cd levels were <2µg/g creatinine but was positive in those whose urinary Cd levels were 2-5µg/g creatinine or >5µg/g creatinine. The urinary ß2-MG levels found in individuals whose urinary Cd levels were >2µg/g creatinine suggest that previous Cd-induced renal tubular damage had occurred.

Differences in the susceptibility to cadmium-induced renal tubular damage and osteoporosis according to sex.

This study aimed to estimate the risks for renal tubular damage and osteoporosis in individuals with long-term environmental Cd exposure. This cross-sectional study comprised 1086 residents living in the vicinity of a copper refinery plant. As the urinary Cd levels increased, the proportion of female subjects with ß2-MG ≥300 µg/g creatinine also increased significantly, but this was not observed in the male subjects. The prevalence of osteoporosis was significantly higher in men with urinary Cd >5 µg/g creatinine than in those with urinary Cd ≤5 µg/g creatinine. This difference was not observed in the corresponding female groups. The association between increased urinary excretion of ß2-MG and decreased BMD was statistically significant only in the female subjects. We suggest that an increased Cd body burden directly decreases the BMD in male subjects; however, in female subjects, it first induces renal microtubular damage, which can lead to osteoporosis.

Risk of gastric cancer is associated with PRKAA1 gene polymorphisms in Koreans.

AIM: To evaluate the association between genetic polymorphisms of the gene encoding AMP-activated protein kinase (PRKAA1) and the risk of gastric cancer. METHODS: The study subjects consisted of 477 age- and sex-matched case-control pairs. Genotyping was performed for 5 tag single nucleotide polymorphisms (SNPs): rs13361707, rs154268, rs3805486, rs6882903, and rs10074991. Associations between gastric cancer and putative risk factors (including the SNPs) were analyzed with multivariate conditional logistic regression models, after adjusting for potential confounding factors. Multiple testing corrections were implemented following methodology for controlling the false discovery rate. Gene-based association tests were performed by using the versatile gene-based association study (VEGAS) method. RESULTS: In the dominant model, SNPs rs13361707 [odds ratio (OR) = 1.51, 95%CI: 1.07-2.11)], rs154268 (OR = 1.65, 95%CI: 1.22-2.22), rs6882903 (OR = 1.48, 95%CI: 1.09-2.00), and rs10074991 (OR = 1.53, 95%CI: 1.09-2.16) were significantly associated with an increased risk of gastric cancer. In the recessive model, SNPs rs154268 (OR = 1.66, 95%CI: 1.22-2.26), rs3805486 (OR = 0.63, 95%CI: 0.46-0.85), and rs10074991 (OR = 1.47, 95%CI: 1.15-1.88) were significant risk or protective factors for gastric cancer. In the codominant model, the ORs of each of the 5 SNPs were statistically significant. All SNPs in the model showed a dose-response relationship between the minor allele frequency and the risk of gastric cancer. Most notably, subjects with a homozygous minor allele in SNP rs10074991 showed 2.15 times the risk of gastric cancer as subjects without a minor allele. The PRKAA1 gene showed a significant gene-based association with gastric cancer in the VEGAS test. CONCLUSION: All 5 tested tag SNPs of the PRKAA1 gene (rs13361707, rs154268, rs3805486, rs6882903, and rs10074991) were significantly associated with gastric cancer.

Evaluation of the relationship between dietary factors, CagA-positive Helicobacter pylori infection, and RUNX3 promoter hypermethylation in gastric cancer tissue.

AIM: To evaluate the relationship among Helicobacter pylori (H. pylori) infection, CagA status, and dietary factors with RUNX3 promoter hypermethylation. METHODS: Gastric cancer tissue samples were collected from 184 South Korean patients. All patients were interviewed following a semi-quantitative food frequency questionnaire. The average frequencies of intake and portion sizes of 89 common food items were documented, and total intakes of calories, nutrients, vitamins, and minerals were calculated for each subject. DNA was extracted from gastric cancer tissue samples, and amplification of the HSP60 gene was performed to detect H. pylori infection. Nested polymerase chain reaction (PCR) was used to detect the presence of the CagA gene. RUNX3 gene expression was measured by reverse transcription-PCR, and RUNX3 methylation status was evaluated by methylation-specific PCR. The odds ratios (ORs) and 95%CI associated with RUNX3 promoter hypermethylation status were estimated for each of the food groups, lifestyle factors, and the interaction between dietary and lifestyle factors with CagA status of H. pylori infection. RESULTS: Overall, 164 patients (89.1%) were positive for H. pylori DNA, with the CagA gene detected in 59 (36%) of these H. pylori-positive samples. In all, 106 (57.6%) patients with gastric cancer demonstrated CpG island hypermethylation at the RUNX3 promoter. RUNX3 expression was undetectable in 52 (43.7%) of the 119 gastric cancer tissues sampled. A high consumption of eggs may increase the risk of RUNX3 methylation in gastric cancer patients, having a mean OR of 2.15 (range, 1.14-4.08). A significantly increased OR of 4.28 (range, 1.19-15.49) was observed with a high consumption of nuts in patients with CagA-positive H. pylori infection. High intakes of carbohydrate, vitamin B1, and vitamin E may decrease the risk of RUNX3 methylation in gastric cancer tissue, particularly in CagA- or H. pylori-negative infection, with OR of 0.41 (0.19-0.90), 0.42 (0.20-0.89), and 0.29 (0.13-0.62), respectively. A high consumption of fruits may protect against RUNX3 methylation. CONCLUSION: These results suggest that the CagA status of H. pylori infection may be a modifier of dietary effects on RUNX3 methylation in gastric cancer tissue.

ITGA1 polymorphisms and haplotypes are associated with gastric cancer risk in a Korean population.

AIM: To evaluate the association between the genetic polymorphisms and haplotypes of the ITGA1 gene and the risk of gastric cancer. METHODS: The study subjects were 477 age- and sex-matched case-control pairs. Genotyping was performed for 15 single nucleotide polymorphisms (SNPs) in ITGA1. The associations between gastric cancer and these SNPs and haplotypes were analyzed with multivariate conditional logistic regression models. Multiple testing corrections were carried out following methodology for controlling the false discovery rate. Gene-based association tests were performed using the versatile gene-based association study (VEGAS) method. RESULTS: In the codominant model, the ORs for SNPs rs2432143 (1.517; 95%CI: 1.144-2.011) and rs2447867 (1.258; 95%CI: 1.051-1.505) were statistically significant. In the dominant model, polymorphisms of rs1862610 and rs2447867 were found to be significant risk factors, with ORs of 1.337 (95%CI: 1.029-1.737) and 1.412 (95%CI: 1.061-1.881), respectively. In the recessive model, only the rs2432143 polymorphism was significant (OR = 1.559, 95%CI: 1.150-2.114). The C-C type of ITGA1 haplotype block 2 was a significant protective factor against gastric cancer in the both codominant model (OR = 0.602, 95%CI: 0.212-0.709, P = 0.021) and the dominant model (OR = 0.653, 95%CI: 0.483-0.884). The ITGA1 gene showed a significant gene-based association with gastric cancer in the VEGAS test. In the dominant model, the A-T type of ITGA1 haplotype block 2 was a significant risk factor (OR = 1.341, 95%CI: 1.034-1.741). SNP rs2447867 might be related to the severity of gastric epithelial injury due to inflammation and, thus, to the risk of developing gastric cancer. CONCLUSION: ITGA1 gene SNPs rs1862610, rs24321 43, and rs2447867 and the ITGA1 haplotype block that includes SNPs rs1862610 and rs2432143 were significantly associated with gastric cancer.

Polycyclic aromatic hydrocarbon-induced oxidative stress, antioxidant capacity, and the risk of lung cancer: a pilot nested case-control study.

AIM: We conducted a pilot nested case-control study to prospectively evaluate the effects of polycyclic aromatic hydrocarbons (PAH) exposure, antioxidant capacity, and oxidative stress on lung carcinogenesis. MATERIALS AND METHODS: Thirty-five patients with lung cancer and 140 age- and sex-matched controls were selected from a sub-cohort of the Korean Multi-center Cancer Cohort. PAH metabolites (1-hydroxypyrene and 2-naphthol), oxidative stress markers, and total antioxidant capacity (TAC) were assessed using urine samples collected at baseline. RESULTS: The levels of urinary PAH metabolites and oxidative stress were not different between cases and controls. Urinary 1-hydroxypyrene and 2-naphthol levels were significantly associated with urinary oxidative stress markers only in lung cancer cases. Individuals with low urinary TAC and high urinary oxidative stress levels had significantly higher risk of lung cancer compared to those with high urinary TAC and low urinary oxidative stress levels. CONCLUSION: Oxidative stress induced by PAH exposure and TAC may be important determinants for the susceptibility to lung cancer.

Goodness-of-Fits of the Spirometric Reference Values for Koreans and USA Caucasians to Spirometry Data from Residents of a Region within Chungbuk Province.

BACKGROUND: Korean regression models for spirometric reference values are different from those of Americans. Using spirometry results of Korean adults, goodness-of-fits of the Korean and the USA Caucasian regression models for forced vital capacity (FVC) and forced expiratory volume in one second (FEV(1)) were compared. METHODS: The number of study participants was 2,360 (1,124 males and 1,236 females). Spirometry was performed under the guidelines of the American Thoracic Society and the European Respiratory Society. After excluding unsuitable participants, spirometric data for 729 individuals (105 males and 624 females) was included in the statistical analysis. The estimated FVC and FEV(1) values were compared with those measured. Goodness-of-fits for Korean and USA Caucasian models were compared using an F-test. RESULTS: In males, the expected values of FVC and FEV(1) using the Korean model were 12.5% and 5.7% greater than those measured, respectively. The corresponding values for the USA Caucasian model were 3.5% and 0.6%. In females, the difference in FVC and FEV(1) were 13.5% and 7.7% for the Korean model, and 6.3% and 0.4% for the USA model, respectively. Goodness-of-fit for the Korean model regarding FVC was not good to the study population, but the Korean regression model for FEV(1), and the USA Caucasian models for FVC and FEV(1) showed good fits to the measured data. CONCLUSION: These results suggest that the USA Caucasian model correlates better to the measured data than the Korean model. Using reference values derived from the Korean model can lead to an overestimation regarding the prevalence of abnormal lung function.

[Effects of oxidative DNA damage and genetic polymorphism of the glutathione peroxidase 1 (GPX1) and 8-oxoguanine glycosylase 1 (hOGG1) on lung cancer].

OBJECTIVES: Oxidative DNA damage is a known risk factor of lung cancer. The glutathione peroxidase (GPX) antioxidant enzyme that reduces hydrogen peroxide and lipid peroxides plays a significant role in protecting cells from the oxidative stress induced by reactive oxygen species. The aim of this case-control study was to investigate effects of oxidative stress and genetic polymorphisms of the GPX1 genes and the interaction between them in the carcinogenesis of lung cancer. METHODS: Two hundreds patients with lung cancer and 200 age- and sex-matched controls were enrolled in this study. Every subject was asked to complete a questionnaire concerning their smoking habits and their environmental exposure to PAHs. The genotypes of the GPX1 and 8-oxoguanine glycosylase 1 (hOGG1) genes were examined and the concentrations of urinary 1-hydroxypyrene (1-OHP), 2-naphthol and 8-hydroxydeoxyguanosine (8-OH-dG) were measured. RESULTS: Cigarette smoking was a significant risk factor for lung cancer. The levels of urinary 8-OH-dG were higher in the patients (p < 0.001), whereas the urinary 1-OHP and 2-naphthol levels were higher in the controls. The GPX1 codon 198 polymorphism was associated with an increased risk of lung cancer. Individuals carrying the Pro/Leu or Leu/Leu genotype of GPX1 were at a higher risk for lung cancer (adjusted OR = 2.29). In addition, these individuals were shown to have high urinary 8-OH-dG concentrations compared to the individuals with the GPX1 Pro/Pro genotype. On the other hand, the polymorphism of the hOGG1 gene did not affect the lung cancer risk and the oxidative DNA damage. CONCLUSIONS: These results lead to a conclusion that individuals with the GPX1 Pro/Leu or Leu/Leu genotype would be more susceptible to the lung cancer induced by oxidative stress than those individuals with the Pro/Pro genotype.