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1.  No Association between Tumor Necrosis Factor-alpha Gene Polymorphisms and Lung Cancer Risk 
The role of genetic polymorphisms of tumor necrosis factor-alpha (TNF-α) for lung cancer development was evaluated.
Genotypes of the TNF-α polymorphisms, -1210C>T, -487A>G, -417A>G, IVS1+123G>A, and IVS3+51A>G, were determined in 616 lung cancer cases and 616 lung cancer-free controls.
After adjusting for body mass index and smoking, each TNF-α genotype or haplotype composed of five TNF-α single nucleotide polymorphisms did not show an association with lung cancer risk (p>0.05). The statistical power was found to be 88.4%, 89.3%, 93.3%, 69.7%, and 93.9% for 1210C>T, -487A>G, -417A>G, IVS1+123G>A, and IVS3+51A>G, respectively. Furthermore, the effects of each SNP or haplotype on lung cancer risk were not found to be different according to the cell type of lung cancer (p>0.05). In the repeated analysis with only subjects without other diseases related to inflammation, there was also no association between polymorphisms or haplotypes of the TNF-α gene and lung cancer risk (p>0.05).
This study found no association between common variants of the TNF-α gene and lung cancer risk.
PMCID: PMC3842450  PMID: 24303348
Lung cancer risk; Polymorphism; Tumor necrosis factor-alpha
2.  PM10 Exposure and Non-accidental Mortality in Asian Populations: A Meta-analysis of Time-series and Case-crossover Studies 
We investigated the association between particulate matter less than 10 µm in aerodynamic diameter (PM10) exposure and non-accidental mortality in Asian populations by meta-analysis, using both time-series and case-crossover analysis.
Among the 819 published studies searched from PubMed and EMBASE using key words related to PM10 exposure and non-accidental mortality in Asian countries, 8 time-series and 4 case-crossover studies were selected for meta-analysis after exclusion by selection criteria. We obtained the relative risk (RR) and 95% confidence intervals (CI) of non-accidental mortality per 10 µg/m3 increase of daily PM10 from each study. We used Q statistics to test the heterogeneity of the results among the different studies and evaluated for publication bias using Begg funnel plot and Egger test.
Testing for heterogeneity showed significance (p<0.001); thus, we applied a random-effects model. RR (95% CI) per 10 µg/m3 increase of daily PM10 for both the time-series and case-crossover studies combined, time-series studies relative risk only, and case-crossover studies only, were 1.0047 (1.0033 to 1.0062), 1.0057 (1.0029 to 1.0086), and 1.0027 (1.0010 to 1.0043), respectively. The non-significant Egger test suggested that this analysis was not likely to have a publication bias.
We found a significant positive association between PM10 exposure and non-accidental mortality among Asian populations. Continued investigations are encouraged to contribute to the health impact assessment and public health management of air pollution in Asian countries.
PMCID: PMC3567321  PMID: 23407325
PM10; Non-accidental mortality; Asia; Meta-analysis
3.  Genetic variant in TP63 on locus 3q28 is associated with risk of lung adenocarcinoma among never-smoking females in Asia 
Hosgood, H. Dean | Wang, Wen-Chang | Hong, Yun-Chul | Wang, Jiu-Cun | Chen, Kexin | Chang, I-Shou | Chen, Chien-Jen | Lu, Daru | Yin, Zhihua | Wu, Chen | Zheng, Wei | Qian, Biyun | Park, Jae Yong | Kim, Yeul Hong | Chatterjee, Nilanjan | Chen, Ying | Chang, Gee-Chen | Hsiao, Chin-Fu | Yeager, Meredith | Tsai, Ying-Huang | Wei, Hu | Kim, Young Tae | Wu, Wei | Zhao, Zhenhong | Chow, Wong-Ho | Zhu, Xiaoling | Lo, Yen-Li | Sung, Sook Whan | Chen, Kuan-Yu | Yuenger, Jeff | Kim, Joo Hyun | Huang, Liming | Chen, Ying-Hsiang | Gao, Yu-Tang | Kim, Jin Hee | Huang, Ming-Shyan | Jung, Tae Hoon | Caporaso, Neil | Zhao, Xueying | Huan, Zhang | Yu, Dianke | Kim, Chang Ho | Su, Wu-Chou | Shu, Xiao-Ou | Kim, In-San | Bassig, Bryan | Chen, Yuh-Min | Cha, Sung Ick | Tan, Wen | Chen, Hongyan | Yang, Tsung-Ying | Sung, Jae Sook | Wang, Chih-Liang | Li, Xuelian | Park, Kyong Hwa | Yu, Chong-Jen | Ryu, Jeong-Seon | Xiang, Yongbing | Hutchinson, Amy | Kim, Jun Suk | Cai, Qiuyin | Landi, Maria Teresa | Lee, Kyoung-Mu | Hung, Jen-Yu | Park, Ju-Yeon | Tucker, Margaret | Lin, Chien-Chung | Ren, Yangwu | Perng, Reury-Perng | Chen, Chih-Yi | Jin, Li | Chen, Kun-Chieh | Li, Yao-Jen | Chiu, Yu-Fang | Tsai, Fang-Yu | Yang, Pan-Chyr | Fraumeni, Joseph F. | Seow, Adeline | Lin, Dongxin | Zhou, Baosen | Chanock, Stephen | Hsiung, Chao Agnes | Rothman, Nathaniel | Lan, Qing
Human genetics  2012;131(7):10.1007/s00439-012-1144-8.
A recent genome-wide association study (GWAS) of subjects from Japan and South Korea reported a novel association between the TP63 locus on chromosome 3q28 and risk of lung adenocarcinoma (p = 7.3 × 10−12); however, this association did not achieve genome-wide significance (p < 10−7) among never-smoking males or females. To determine if this association with lung cancer risk is independent of tobacco use, we genotyped the TP63 SNPs reported by the previous GWAS (rs10937405 and rs4488809) in 3,467 never-smoking female lung cancer cases and 3,787 never-smoking female controls from 10 studies conducted in Taiwan, Mainland China, South Korea, and Singapore. Genetic variation in rs10937405 was associated with risk of lung adenocarcinoma [n = 2,529 cases; p = 7.1 × 10−8; allelic risk = 0.80, 95% confidence interval (CI) = 0.74–0.87]. There was also evidence of association with squamous cell carcinoma of the lung (n = 302 cases; p = 0.037; allelic risk = 0.82, 95% CI = 0.67–0.99). Our findings provide strong evidence that genetic variation in TP63 is associated with the risk of lung adenocarcinoma among Asian females in the absence of tobacco smoking.
PMCID: PMC3875137  PMID: 22367405
4.  Association between Prenatal Exposure to Cadmium and Atopic Dermatitis in Infancy 
Journal of Korean Medical Science  2013;28(4):516-521.
Our objective was to evaluate the relationship between intrauterine exposure to cadmium and the presence of atopic dermatitis in infants 6 months of age, adjusted for covariates including exposure to other heavy metals. The present research is a component of the Mothers' and Children's Environmental Health (MOCEH) study, a multi-center birth cohort project conducted in Korea. Study subjects were restricted to pregnant women in whom cadmium and lead levels were measured at delivery and whose infants were assessed for the presence of atopic disease at 6 months of age. The odds ratio (OR) for the presence of atopic dermatitis in 6-month-old infants whose cord blood had elevated cadmium levels, after adjustment for other covariates, was 2.350 (95% CI, 1.126-4.906). The OR for the presence of atopic dermatitis in infants whose cord blood had elevated lead levels was not significant. In the present study, the cord blood cadmium level was significantly associated with the presence of atopic dermatitis in 6-month-old infants; this was not true of the cord blood lead level. To the best of our knowledge, this is the first prospective study to show a relationship between prenatal exposure to cadmium and atopic dermatitis in infancy.
PMCID: PMC3617302  PMID: 23580123
Atopy; Cadmium; Lead; Cord; Dermatitis, Atopic
5.  Aging Society and Environmental Health Challenges 
Environmental Health Perspectives  2013;121(3):a68-a69.
PMCID: PMC3621200  PMID: 23454410
6.  GSTM1, GSTT1, and GSTP1 Polymorphisms and Associations between Air Pollutants and Markers of Insulin Resistance in Elderly Koreans 
Environmental Health Perspectives  2012;120(10):1378-1384.
Background: Previous studies have suggested that diabetes mellitus (DM) is an outcome of exposure to air pollution, and metabolic detoxification genes affect air pollution–related outcomes.
Objectives: We evaluated associations between air pollutants and markers of insulin resistance (IR), an underlying mechanism of type 2 DM, and effect modification by GSTM1, GSTT1, and GSTP1 genotypes among elderly participants in the Korean Elderly Environmental Panel (KEEP) study.
Methods: We recruited 560 people ≥ 60 years of age and obtained blood samples from them up to three times between 2008 and 2010. For air pollution exposure, we used ambient air pollutant [i.e., particulate matter ≤ 10 µm in diameter (PM10), sulfur dioxide (SO2), ozone (O3), and nitrogen dioxide (NO2)] monitoring data. We measured levels of fasting glucose and insulin and derived the homeostatic model assessment (HOMA) index to assess IR. Mixed-effect models were used to estimate associations between air pollutants and IR indices on the same day or lagged up to 10 days prior, and effect modification by GSTM1, GSTT1, and GSTP1 genotypes.
Results: Interquartile range increases in PM10, O3, and NO2 were significantly associated with IR indices, depending on the lag period. Associations were stronger among participants with a history of DM and among those with GSTM1-null, GSTT1-null, and GSTP1 AG or GG genotypes.
Conclusions: Our results suggest that PM10, O3, and NO2 may increase IR in the elderly, and that GSTM1-null, GSTT1-null, and GSTP1 AG or GG genotypes may increase susceptibility to potential effects of ambient air pollutants on IR.
PMCID: PMC3491923  PMID: 22732554
air pollution; elderly; genetic polymorphism; insulin resistance
7.  Air Pollution and Symptoms of Depression in Elderly Adults 
Environmental Health Perspectives  2012;120(7):1023-1028.
Background: Although the effect of air pollution on various diseases has been extensively investigated, few studies have examined its effect on depression.
Objectives: We investigated the effect of air pollution on symptoms of depression in an elderly population.
Methods: We enrolled 537 participants in the study who regularly visited a community center for the elderly located in Seoul, Korea. The Korean version of the Geriatric Depression Scale-Short Form (SGDS-K) was used to evaluate depressive symptomatology during a 3-year follow-up study. We associated ambient air pollutants with SGDS-K results using generalized estimating equations (GEE). We also conducted a factor analysis with items on the SGDS-K to determine which symptoms were associated with air pollution.
Results: SGDS-K scores were positively associated with interquartile range (IQR) increases in the 3-day moving average concentration of particulate matter with an aerodynamic diameter ≤ 10 μm (PM10) [17.0% increase in SGDS-K score, 95% confidence interval (CI): 4.9%, 30.5%], the 0–7 day moving average of nitrogen dioxide [NO2; 32.8% (95% CI: 12.6%, 56.6%)], and the 3-day moving average of ozone [O3; 43.7% (95% CI: 11.5%, 85.2%)]. For these three pollutants, factor analysis showed that air pollution was more strongly associated with emotional symptoms such as feeling happy and satisfied than with somatic or affective symptoms.
Conclusions: Our study suggests that increases in PM10, NO2, and O3 may increase depressive symptoms among the elderly. Of the symptoms evaluated, ambient air pollution was most strongly associated with emotional symptoms.
PMCID: PMC3404652  PMID: 22514209
air pollution; depressive symptoms; elderly; factor analysis; panel study
8.  Association of Serum 25-Hydroxyvitamin D Levels with Markers for Metabolic Syndrome in the Elderly: A Repeated Measure Analysis 
Journal of Korean Medical Science  2012;27(6):653-660.
The purpose of current study was to investigate associations of serum 25-hydroxyvitamin D (OHVD) levels with markers for metabolic syndrome in elderly Koreans. We conducted a panel study on 301 individuals over 60 yr old in Seoul, Korea, and repeatedly measured serum OHVD, glucose, insulin, and lipid levels. Mixed effect model and generalized estimating equations were used to investigate relationships between serum OHVD levels with marker levels for metabolic syndrome and each of its categories. Of all subjects, 76.6% were vitamin D deficient (< 50 nM) and 16.9% were insufficient (< 75 nM). Inverse association was demonstrated between serum OHVD levels and insulin (P = 0.004), triglyceride (P = 0.023) and blood pressure (systolic blood pressure: P = 0.002; diastolic blood pressure: P < 0.001). Vitamin D deficiency was found to increase risk of 'hypertriglyceridemia' category of metabolic syndrome (odds ratio: 1.73, 95% confidence interval: 1.13-2.66). In conclusion, we found from our repeated measure analysis that decreasing serum OHVD levels are associated with increasing insulin resistance, increasing serum triglyceride levels and increasing blood pressure in elderly Koreans, and confirmed on the risk of 'hypertriglyceridemia' in vitamin D deficient subjects.
PMCID: PMC3369452  PMID: 22690097
Vitamin D; Insulin Resistance; Metabolic Syndrome; Elderly; Mixed Effect Model
10.  Characteristics of Humidifier Use in Korean Pregnant Women: The Mothers and Children's Environmental Health (MOCEH) Study 
The current use of humidifier detergent and its harmful impact on humans has arisen as a societal environmental health issue. Therefore, in this study we aimed to explore the relationship between demo-socio characteristics and humidifier use, as well as the monthly usage changes in pregnant women; thus, we report the actual status of humidifier usage of Korea's pregnant population.
From a birth cohort of a Mothers and Children's Environmental Health (MOCEH) study, 1,144 pregnant women who responded through questionnaires including demo-socio characteristics, obstetric status and household environment including whether they use humidifier and frequency of use were included in this study. Statistical analyses were performed to explore the relationship between maternal characteristics and the relevance of the use of humidifiers was performed using a chi-square test, a t-test and univariate logistic regression analysis. The monthly usage rate was demonstrated in the graph.
The humidifier usage rate in pregnant women was 28.2%. The average frequency of humidifier usage was 4.6 days per week, 7.3 hours per day. The usage rate was higher in the multipara group and the above the age of 34 age group than in the primipara and below the age of 34 groups. Seoul showed a higher usage rate than Cheonan and Ulsan and as the education level and income increased, the usage rate of humidifiers among pregnant women also increased. In the monthly trend of usage rate, the winter season showed the highest usage rate of over 45% and the lowest in late summer and beginning of fall with a value of 12% or less.
During pregnancy, the mother's body is especially vulnerable to hazardous environmental exposure that not only affects the pregnant woman but also the fetus. Further research is still needed to elucidate the route and effect of environmental risk factors. Therefore, based on precautionary and preventive principles, special interest and caution in harmful environments are strongly needed not only at an individual level but also at a national level.
PMCID: PMC3274746  PMID: 22347705
Cohort study; Humidifier; Pregnant woman
11.  Prenatal Exposure to Phthalates and Infant Development at 6 Months: Prospective Mothers and Children’s Environmental Health (MOCEH) Study 
Environmental Health Perspectives  2011;119(10):1495-1500.
Background: There are increasing concerns over adverse effects of prenatal phthalate exposure on the neurodevelopment of infants.
Objectives: Our goal was to explore the association between prenatal di(2-ethylhexyl) phthalate and dibutyl phthalate exposure and the Mental and Psychomotor Developmental Indices (MDI and PDI, respectively) of the Bayley Scales of Infant Development at 6 months, as part of the Mothers and Children’s Environmental Health Study.
Methods: Between 2006 and 2009, 460 mother–infant pairs from Seoul, Cheonan, and Ulsan, Korea, participated. Prenatal mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono-n-butyl phthalate (MBP) were measured in one urine sample acquired from each mother during the third trimester of pregnancy. Associations with log-transformed creatinine-corrected phthalate concentrations were estimated using linear regression models adjusted for potential confounders.
Results: MDI was inversely associated with the natural log concentrations (micrograms per gram creatinine) of MEHHP [β = –0.97; confidence interval (CI), –1.85 to –0.08] and MEOHP (β = –0.95; CI, –1.87 to –0.03), and PDI was inversely associated with MEHHP (β = –1.20; CI, –2.33 to –0.08). In males, MDI was inversely associated with MEHHP (β = –1.46; CI, –2.70 to –0.22), MEOHP (β = –1.57; CI, –2.87 to –0.28), and MBP (β = –0.93; CI, –1.82 to –0.05); PDI was inversely associated with MEHHP (β = –2.36; CI, –3.94 to –0.79), MEOHP (β = –2.05; CI, –3.71 to –0.39), and MBP (β = –1.25; CI, –2.40 to –0.11). No significant linear associations were observed for females.
Conclusions: The results suggest that prenatal exposure to phthalates may be inversely associated with the MDI and PDI of infants, particularly males, at 6 months.
PMCID: PMC3230435  PMID: 21737372
development; dibutyl phthalate; di(2-ethylhexyl) phthalate; infant; prenatal
12.  Hebei Spirit Oil Spill Exposure and Subjective Symptoms in Residents Participating in Clean-Up Activities 
This study was conducted to examine the relationship between crude oil exposure and physical symptoms among residents participating in clean-up work associated with the Hebei Spirit oil spill, 2007 in Korea.
A total of 288 residents responded to a questionnaire regarding subjective physical symptoms, sociodemographic characteristics and clean-up activities that occurred between two and eight weeks after the accident. Additionally, the urine of 154 of the respondents was analyzed for metabolites of volatile organic compounds (VOCs) and polycyclic aromatic hydrocarbons (PAHs) and heavy metals. To compare the urinary levels of exposure biomarkers, the urine of 39 inland residents who were not directly exposed to the oil spill were analyzed.
Residents exposed to oil remnants through clean-up work showed associations between physical symptoms and the exposure levels defined in various ways, including days of work, degree of skin contamination, and levels of some urinary exposure biomarkers of VOCs, metabolites and metals, although no major abnormalities in urinary exposure biomarkers were observed.
This study provides evidence of a relationship between crude oil exposure and acute human health effects and suggests the need for follow-up to evaluate the exposure status and long-term health effects of clean-up participants.
PMCID: PMC3214977  PMID: 22125768
Oil spill; Health effects; Urinary metabolites; VOCs; PAHs
13.  The 5p15.33 Locus Is Associated with Risk of Lung Adenocarcinoma in Never-Smoking Females in Asia 
PLoS Genetics  2010;6(8):e1001051.
Genome-wide association studies of lung cancer reported in populations of European background have identified three regions on chromosomes 5p15.33, 6p21.33, and 15q25 that have achieved genome-wide significance with p-values of 10−7 or lower. These studies have been performed primarily in cigarette smokers, raising the possibility that the observed associations could be related to tobacco use, lung carcinogenesis, or both. Since most women in Asia do not smoke, we conducted a genome-wide association study of lung adenocarcinoma in never-smoking females (584 cases, 585 controls) among Han Chinese in Taiwan and found that the most significant association was for rs2736100 on chromosome 5p15.33 (p = 1.30×10−11). This finding was independently replicated in seven studies from East Asia totaling 1,164 lung adenocarcinomas and 1,736 controls (p = 5.38×10−11). A pooled analysis achieved genome-wide significance for rs2736100. This SNP marker localizes to the CLPTM1L-TERT locus on chromosome 5p15.33 (p = 2.60×10−20, allelic risk = 1.54, 95% Confidence Interval (CI) 1.41–1.68). Risks for heterozygote and homozygote carriers of the minor allele were 1.62 (95% CI; 1.40–1.87), and 2.35 (95% CI: 1.95–2.83), respectively. In summary, our results show that genetic variation in the CLPTM1L-TERT locus of chromosome 5p15.33 is directly associated with the risk of lung cancer, most notably adenocarcinoma.
Author Summary
Worldwide, approximately 15% of lung cancer cases occur among nonsmokers. Genome-wide association studies (GWAS) of lung cancer conducted in populations of European background have identified three regions on chromosomes 5, 6, and 15 that harbor genetic variants that confer risk for lung cancer. Prior studies were conducted primarily in cigarette smokers, raising the possibility that the associations could be related to tobacco use, lung carcinogenesis, or both. A GWAS of lung cancer among never-smokers is an optimal setting to discover effects that are independent of smoking. Since most women in Asia do not smoke, we conducted a GWAS of lung adenocarcinoma among never-smoking females (584 cases, 585 controls) in Taiwan, and observed a region on chromosome 5 significantly associated with risk for lung cancer in never-smoking women. The finding was independently replicated in seven studies from East Asia totaling 1,164 lung adenocarcinomas and 1,736 controls. To our knowledge, this study is the first reported GWAS of lung cancer in East Asian women, and together with the replication studies represents the largest genetic association study in this population. The findings provide insight into the genetic contribution of common variants to lung carcinogenesis.
PMCID: PMC2916850  PMID: 20700438
14.  Relationship between Environmental Phthalate Exposure and the Intelligence of School-Age Children 
Environmental Health Perspectives  2010;118(7):1027-1032.
Concern over phthalates has emerged because of their potential toxicity to humans.
We investigated the relationship between the urinary concentrations of phthalate metabolites and children’s intellectual functioning.
This study enrolled 667 children at nine elementary schools in five South Korean cities. A cross-sectional examination of urine phthalate concentrations was performed, and scores on neuropsychological tests were obtained from both the children and their mothers.
We measured mono-2-ethylhexyl phthalate (MEHP) and mono(2-ethyl-5-oxohexyl)phthalate (MEOHP), both metabolites of di(2-ethylhexyl)phthalate (DEHP), and mono-n-butyl phthalate (MBP), a metabolite of dibutyl phthalate (DBP), in urine samples. The geometric mean (ln) concentrations of MEHP, MEOHP, and MBP were 21.3 μg/L [geometric SD (GSD) = 2.2 μg/L; range, 0.5–445.4], 18.0 μg/L (GSD = 2.4; range, 0.07–291.1), and 48.9 μg/L (GSD = 2.2; range, 2.1–1645.5), respectively. After adjusting for demographic and developmental covariates, the Full Scale IQ and Verbal IQ scores were negatively associated with DEHP metabolites but not with DBP metabolites. We also found a significant negative relationship between the urine concentrations of the metabolites of DEHP and DBP and children’s vocabulary subscores. After controlling for maternal IQ, a significant inverse relationship between DEHP metabolites and vocabulary subscale score remained. Among boys, we found a negative association between increasing MEHP phthalate concentrations and the sum of DEHP metabolite concentrations and Wechsler Intelligence Scale for Children vocabulary score; however, among girls, we found no significant association between these variables.
Controlling for maternal IQ and other covariates, the results show an inverse relationship between phthalate metabolites and IQ scores; however, given the limitations in cross-sectional epidemiology, prospective studies are needed to fully explore these associations.
PMCID: PMC2920903  PMID: 20194078
children; cognition; dibutyl phthalate (DBP); di(2-ethylhexyl)phthalate (DEHP); IQ; mono-2-ethylhexyl phthalate (MEHP); mono(2-ethyl-5-oxohexyl) phthalate (MEOHP); mono-n-butyl phthalate (MBP); phthalate; sex
15.  Seasonal variation of effect of air pollution on blood pressure 
Many studies have shown a consistent association between ambient air pollution and an increase in death due to cardiovascular causes. An increase in blood pressure is a common risk factor for a variety of cardiovascular diseases. However, the association between air pollution and blood pressure has not been evaluated extensively.
In this cross‐sectional study, we measured blood pressure in 10 459 subjects who had a health examination from 2001 to 2003, and calculated individual's exposure to ambient levels of air pollutants. To evaluate the relationship between exposure to air pollutants and blood pressure with respect to season, we performed a multiple regression analysis, separately, according to season, controlling for individual characteristics and meteorological variables.
In the warm‐weather season (July–September), particulate air pollutant of <10 μm (PM10) and nitrogen dioxide (NO2) concentrations were significantly associated with measures of blood pressure. During cold weather (October–December), blood pressure was significantly associated with sulphur dioxide (SO2) and ozone (O3) concentrations. The significant association between PM10 or NO2 and blood pressure disappeared during the cold‐weather season.
We found a seasonal variation for the association between ambient air‐pollutant concentrations and blood pressure.
PMCID: PMC2652940  PMID: 17372291
16.  Exposures to Particulate Matter and Polycyclic Aromatic Hydrocarbons and Oxidative Stress in Schoolchildren 
Environmental Health Perspectives  2009;118(4):579-583.
Air pollution is known to contribute to respiratory and cardiovascular mortality and morbidity. Oxidative stress has been suggested as one of the main mechanisms for these effects on health.
The aim of this study was to analyze the effects of exposure to particulate matter (PM) with aerodynamic diameters ≤ 10 μm (PM10) and ≤ 2.5 μm (PM2.5) and polycyclic aromatic hydrocarbons (PAHs) on urinary malondialdehyde (MDA) levels in schoolchildren.
The study population consisted of 120 schoolchildren. The survey and measurements were conducted in four cities—two in China (Ala Shan and Beijing) and two in Korea (Jeju and Seoul)—between 4 and 9 June 2007. We measured daily ambient levels of PM and their metal components at the selected schools during the study period. We also measured urinary 1-hydroxypyrene (1-OHP) and 2-naphthol, to assess PAH exposure, and MDA, to assess oxidative stress. Measurements were conducted once a day for 5 consecutive days. We constructed a linear mixed model after adjusting for individual variables to estimate the effects of PM and PAH on oxidative stress.
We found statistically significant increases in urinary MDA levels with ambient PM concentrations from the current day to the 2 previous days (p < 0.0001). Urinary 1-OHP level also showed a positive association with urinary MDA level, which was statistically significant with or without PM in the model (p < 0.05). Outdoor PM and urinary 1-OHP were synergistically associated with urinary MDA levels. Some metals bound to PM10 (aluminum, iron, strontium, magnesium, silicon, arsenic, barium, zinc, copper, and cadmium) and PM2.5 (magnesium, iron, strontium, arsenic, cadmium, zinc, aluminum, mercury, barium, and copper) also had significant associations with urinary MDA level.
Exposure to PM air pollution and PAHs was associated with oxidative stress in schoolchildren.
PMCID: PMC2854738  PMID: 20368125
children; metal; oxidative stress; PAH; panel study; particulate matter
17.  Interaction between GSTM1/GSTT1 Polymorphism and Blood Mercury on Birth Weight 
Environmental Health Perspectives  2009;118(3):437-443.
Mercury (Hg) is toxic to both the reproductive and nervous systems. In addition, glutathione S-transferases (GSTs), which conjugate glutathione to a variety of electrophilic compounds, are involved in the detoxification of Hg.
In this study we examined the association between prenatal exposure to Hg and birth weight as well as the influence of GST polymorphisms.
The total Hg concentration in maternal and cord blood was measured from 417 Korean women and newborns in the Mothers and Children’s Environmental Health study from 2006 to 2008. Information on birth weight was collected from the patients’ medical records. The genotyping of glutathione S-transferase M1 (GSTM1) and glutathione S-transferase T1 (GSTT1) polymorphisms was carried out using polymerase chain reaction. Regression analysis was performed to determine the association between the blood Hg concentration and birth weight in mothers with GSTM1 and GSTT1 polymorphisms.
The geometric mean levels of Hg in the maternal blood during late pregnancy and in cord blood were 3.30 μg/L and 5.53 μg/L, respectively. For mothers with the GSTT1 null genotype, elevated Hg levels in maternal blood during late pregnancy were associated with an increased risk of lower birth weight. For mothers with both GSTM1 and GSTT1 null genotype, both maternal and cord blood Hg levels were associated with lower birth weight.
This study suggests that the interactions of Hg with GSTM1 and GSTT1 polymorphisms play a role in reducing birth weight.
PMCID: PMC2854776  PMID: 20194072
birth weight; GSTM1; GSTT1; mercury; polymorphism; pregnancy
18.  Differential oxidative stress response in young children and the elderly following exposure to PM2.5 
The mechanism of the adverse health effects of ambient particulate matter on humans has not been well-investigated despite many epidemiologic association studies. Measurement of personal exposure to particulate pollutants and relevant biological effect markers are necessary in order to investigate the mechanism of adverse health effects, particularly in fragile populations considered to be more susceptible to the effects of pollutants.
We measured personal exposure to PM2.5 and examined oxidative stress using urinary malondialdehyde three times in 51 preschoolers and 38 elderly subjects. A linear mixed-effects model was used to estimate PM2.5 effects on urinary MDA levels.
Average personal exposure of the children and elderly to PM2.5 was 80.5 ± 29.9 and 20.7 ± 12.7 μg/m3, respectively. Mean urinary MDA level in the children and the elderly was 3.6 ± 1.9 and 4.0 ± 1.6 μmol/g creatinine. For elderly subjects the PM2.5 level was significantly associated with urinary MDA after adjusting for age, sex, BMI, passive smoking, day-care facility site, alcohol consumption, cigarette smoking, and medical history (heart disease, hypertension and bronchial asthma). However, there was no significant relationship for children.
The elderly were more susceptible than young children to oxidative stress as a result of ambient exposure to PM2.5. Identification of oxidative stress induced by PM2.5 explains the mechanism of adverse health effects such as cardiovascular or respiratory diseases, particularly in the elderly.
PMCID: PMC2684767  PMID: 19568869
Particulate matter; Oxidative stress; Repeated measurement; Malondialdehyde; Biological markers
19.  The Mothers and Children’s Environmental Health (MOCEH) study 
European Journal of Epidemiology  2009;24(9):573-583.
The MOCEH study is a prospective hospital- and community-based cohort study designed to collect information related to environmental exposures (chemical, biological, nutritional, physical, and psychosocial) during pregnancy and childhood and to examine how exposure to environmental pollutants affects growth, development, and disease. The MOCEH network includes one coordinating center, four local centers responsible for recruiting pregnant women, and four evaluation centers (a nutrition center, bio-repository center, neurocognitive development center, and environment assessment center). At the local centers, trained nurses interview the participants to gather information regarding their demographic and socioeconomic characteristics, complications related to the current gestation period, health behaviors and environmental factors. These centers also collect samples of blood, placenta, urine, and breast milk. Environmental hygienists measure each participant’s level of exposure to indoor and outdoor pollutants during the pre- and postnatal periods. The participants are followed up through delivery and until the child is 5 years of age. The MOCEH study plans to recruit 1,500 pregnant women between 2006 and 2010 and to perform follow-up studies on their children. We expect this study to provide evidence to support the hypothesis that the gestational environment has an effect on the development of diseases during adulthood. We also expect the study results to enable evaluation of latency and age-specific susceptibility to exposure to hazardous environmental pollutants, evaluation of growth retardation focused on environmental and genetic risk factors, selection of target environmental diseases in children, development of an environmental health index, and establishment of a national policy for improving the health of pregnant women and their children.
PMCID: PMC2744774  PMID: 19629723
Prenatal exposures; Child development; Cohort study; Design
20.  Investigation on Health Effects of an Abandoned Metal Mine 
Journal of Korean Medical Science  2008;23(3):452-458.
To investigate potential health risks associated with exposure to metals from an abandoned metal mine, the authors studied people living near an abandoned mine (n=102) and control groups (n=149). Levels of cadmium, copper, arsenic, lead, and zinc were measured in the air, soil, drinking water, and agricultural products. To assess individual exposure, biomarkers of each metal in blood and urine were measured. β2-microglobulin, α1-microglobulin, and N-acetyl-beta-glucosaminidase and bone mineral density were measured. Surface soil in the study area showed 2-10 times higher levels of metals compared to that of the control area. Metal concentrations in the groundwater and air did not show any notable differences between groups. Mean concentrations of cadmium and copper in rice and barley from the study area were significantly higher than those of the control area (p<0.05). Geometric means of blood and urine cadmium in the study area were 2.9 µg/L and 1.5 µg/g Cr, respectively, significantly higher than those in the control area (p<0.05). There were no differences in the levels of urinary markers of early kidney dysfunction and bone mineral density. The authors conclude that the residents near the abandoned mine were exposed to higher levels of metals through various routes.
PMCID: PMC2526532  PMID: 18583882
Abandoned Metal Mine; Health Risk; Biological Markers; Kidney Dysfunction
21.  Temporal Changes of Lung Cancer Mortality in Korea 
Journal of Korean Medical Science  2007;22(3):524-528.
The lung cancer mortality in Korea has increased remarkably during the last 20 yr, and, it has become the first leading cause of cancer-related deaths since 2000. The aim of the current study was to examine time trends of lung cancer mortality during the period 1984-2003 in Korea, assessing the effects of age, period, and birth cohort. Data on the annual number of deaths due to lung cancer and on population statistics from 1984 to 2003 were obtained from the Korea National Statistical Office. A log-linear Poisson age-period-cohort model was used to estimate the effects of age, period, and birth cohort. The both trends of male and female lung cancer mortality were both explained by age-period-cohort models. The risks of lung cancer mortalities for both genders were shown to decline in recent birth cohorts. The decreasing trends begin with the 1939 birth cohort for men and 1959 for women. The mortality pattern of lung cancer was dominantly explained by a birth cohort effect, possibly related with the change in smoking pattern, for both men and women. Finally, the mortality of lung cancer in Korea is expected to further increase in both men and women for a while.
PMCID: PMC2693649  PMID: 17596665
Cohort Effect; Lung Neoplasms; Mortality; Korea; Smoking; Linear Models
22.  Metals in Particulate Pollutants Affect Peak Expiratory Flow of Schoolchildren 
Environmental Health Perspectives  2006;115(3):430-434.
The contribution of the metal components of particulate pollutants to acute respiratory effects has not been adequately evaluated. Moreover, little is known about the effects of genetic polymorphisms of xenobiotic metabolism on pulmonary function.
This study was conducted to assess lung function decrement associated with metal components in particulate pollutants and genetic polymorphisms of glutathione S-transferase M1 and T1.
We studied 43 schoolchildren who were in the 3rd to 6th grades. Each student measured peak expiratory flow rate three times a day for 42 days. Particulate air concentrations were monitored every day, and the concentrations of iron, manganese, lead, zinc, and aluminum in the particles were measured. Glutathione S-transferase M1 and T1 genetic polymorphisms were determined using DNA extracted from participant buccal washings. We used a mixed linear regression model to estimate the association between peak expiratory flow rate and particulate air pollutants.
We found significant reduction in the peak expiratory flow rate after the children’s exposure to particulate pollutants. The effect was shown most significantly 1 day after exposure to the ambient particles. Manganese and lead in the particles also reduced the peak expiratory flow rate. Genetic polymorphisms of glutathione S-transferase M1 and T1 did not significantly affect peak expiratory flow rate.
This study demonstrated that particulate pollutants and metals such as manganese and lead in the particles are associated with a decrement of peak expiratory flow rate. These effects were robust even with consideration of genetic polymorphisms of glutathione S-transferase.
PMCID: PMC1849935  PMID: 17431494
air pollution; genetic polymorphism; lung function; metals; particles
23.  GSTM1 and GSTP1 Polymorphisms as Potential Factors for Modifying the Effect of Smoking on Inflammatory Response 
Journal of Korean Medical Science  2006;21(6):1021-1027.
Inflammation has been known to be an important underlying condition for development of various diseases including cancer. The aims of this study were to investigate whether tobacco smoke exposure increases the level of inflammation biomarkers and the GSTM1 and GSTP1 gene polymorphisms are associated with inflammatory response due to tobacco smoke exposure. We measured urinary cotinine level in 300 healthy university students. Total serum TNF-α levels and blood WBC counts were determined to evaluate inflammatory response. Allelic loss of the GSTM1 and the GSTP1 (Ile105Val) polymorphism were determined by PCR and RFLP. Tobacco smoke exposure was found to be associated with increase of both TNF-α level and WBC count. Particularly, smokers with combination of GSTM1 null and GSTP1 AG or GG genotypes showed higher TNF-α level than those with the other genotype combinations (p=0.07). This result suggests that smoking may induce inflammation measured as TNF-α level or WBC count and combinations of the GSTM1 and GSTP1 polymorphisms may modify the effect of smoking on serum TNF-α level.
PMCID: PMC2721922  PMID: 17179680
Smoking; Inflammation; Tumor Necrosis Factor-alpha; Leukocytes; glutathione S-transferase M1; Glutathione S-Transferase pi; Polymorphism, Genetic
24.  Benzo[a]pyrene-induced DNA-protein crosslinks in cultured human lymphocytes and the role of the GSTM1 and GSTT1 genotypes. 
Journal of Korean Medical Science  2002;17(3):316-321.
We investigated the influence of glutathione S-transferase M1 (GSTM1) and glutathione S-transferase T1 (GSTT1) polymorphisms upon DNA-protein crosslinks (DPC) induced by benzo[a]pyrene (B[a]P) in cultured human lymphocytes. Lymphocyte samples were collected from 30 healthy nonsmoking hospital administrative workers. DPC was detected with KCl-SDS assay and the distributions of GSTM1 and GSTT1 were determined by polymerase chain reaction. B[a]P was found to induce a significant dose-responsive increase in cytotoxicity and DPC regardless of the genotypes (p<0.05). We did not find statistically significant genetic modification effect of GSTM1 and GSTT1 polymorphisms in the cytotoxicity and DPC formation (p>0.05). In terms of the genes examined, the level of cytotoxicity and DPC formation were found to be highest in the GSTM1-null and GSTT1-null cells. In conclusion, B[a]P induced a significant increase in the cytotoxicity and the level of DPC formation in cultured human lymphocytes. Our findings suggest that DPC could be used as a biomarker of B[a]P exposure.
PMCID: PMC3054882  PMID: 12068133
25.  Effects of air pollutants on acute stroke mortality. 
Environmental Health Perspectives  2002;110(2):187-191.
The relationship between stroke and air pollution has not been adequately studied. We conducted a time-series study to examine the evidence of an association between air pollutants and stroke over 4 years (January 1995-December 1998) in Seoul, Korea. We used a generalized additive model to regress daily stroke death counts for each pollutant, controlling for seasonal and long-term trends and meteorologic influences, such as temperature, relative humidity, and barometric pressure. We observed an estimated increase of 1.5% [95% confidence interval (CI), 1.3-1.8%] and 2.9% (95% CI, 0.3-5.5%) in stroke mortality for each interquartile range increase in particulate matter < 10 microm aerodynamic diameter (PM(10)) and ozone concentrations in the same day. Stroke mortality also increased 3.1% (95% CI, 1.1-5.1%) for nitrogen dioxide, 2.9% (95% CI, 0.8-5.0%) for sulfur dioxide, and 4.1% (95% CI, 1.1-7.2%) for carbon monoxide in a 2-day lag for each interquartile range increase in single-pollutant models. When we examined the associations among PM(10) levels stratified by the level of gaseous pollutants and vice versa, we found that these pollutants are interactive with respect to their effects on the risk of stroke mortality. We also observed that the effects of PM(10) on stroke mortality differ significantly in subgroups by age and sex. We conclude that PM(10) and gaseous pollutants are significant risk factors for acute stroke death and that the elderly and women are more susceptible to the effect of particulate pollutants.
PMCID: PMC1240734  PMID: 11836148

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