Association between short-term exposure to ambient air pollutants and biomarkers indicative of inflammation and oxidative stress: a cross-sectional study using KoGES-HEXA data.

BACKGROUND: Air pollution-induced systemic inflammation and oxidative stress are hypothesized to be the major biological mechanisms underlying pathological outcomes. We examined the association between short-term exposure to ambient air pollutants and biomarkers of inflammation and oxidative stress in 2199 general middle-aged Korean population residing in metropolitan areas. METHODS: Serum levels of inflammatory cytokines (interleukin [IL]-1ß, IL-6, IL-8, IL-10, and tumor necrosis factor [TNF]-α) and urinary levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) were measured. Daily concentrations of a series of air pollutants (particulate matter [PM]10, PM2.5, SO2, NO2, CO, and O3) were predicted using the Community Multiscale Air Quality modeling system, and participant-level pollutant exposure was determined using geocoded residential addresses. Short-term exposure was defined as the 1- to 7-day moving averages. RESULTS: The multivariable-adjusted linear models controlling for the sociodemographic, lifestyle, temporal, and meteorological factors identified positive associations of PM with IL-1ß, IL-8, IL-10, TNF-α, and 8-OHdG levels; SO2 with IL-10 levels, CO with IL-1ß, IL-10, and TNF-α levels; and O3 with IL-1ß, IL-8, and 8-OHdG levels. O3 levels were inversely associated with IL-10 levels. For each pollutant, the strongest associations were observed for the 7-day average PM and CO with IL-1ß (per 10-µg/m3 increase in PM10: 2.7%, 95% confidence interval [CI] = 0.6-4.8; per 10-µg/m3 increase in PM2.5: 6.4%, 95% CI = 2.4-10.5; per 0.1-ppm increase in CO: 3.3%, 95% CI = 0.3-6.5); the 2-day average SO2 with IL-10 levels (per 1-ppb increase in SO2: 1.1%, 95% CI = 0.1-2.1); and the 7-day average O3 with IL-8 levels (per 1-ppb increase in O3: 1.3%, 95% CI = 0.7-1.9). CONCLUSIONS: Short-term exposure to ambient air pollutants may induce oxidative damage and pro-inflammatory roles, together with counter-regulatory anti-inflammatory response.

Integrated dataset of the Korean Genome and Epidemiology Study cohort with estimated air pollution data.

Public concern about the adverse health effects of air pollution has grown rapidly in Korea, and there has been increasing demand for research on ways to minimize the health effects of air pollution. Integrating large epidemiological data and air pollution exposure levels can provide a data infrastructure for studying ambient air pollution and its health effects. The Korean Genome and Epidemiology Study (KoGES), a large population-based study, has been used in many epidemiological studies of chronic diseases. Therefore, KoGES cohort data were linked to air pollution data as a national resource for air pollution studies. Air pollution data were produced using community multiscale air quality modeling with additional adjustment of monitoring data, satellite-derived aerosol optical depth, normalized difference vegetation index, and meteorological data to increase the accuracy and spatial resolution. The modeled air pollution data were linked to the KoGES cohort based on participants' geocoded residential addresses in grids of 1 km (particulate matter) or 9 km (gaseous air pollutants and meteorological variables). As the integrated data become available to all researchers, this resource is expected to serve as a useful infrastructure for research on the health effects of air pollution.

Long-Term Effects of Ambient Particulate and Gaseous Pollutants on Serum High-Sensitivity C-Reactive Protein Levels: A Cross-Sectional Study Using KoGES-HEXA Data.

Ambient air pollutants reportedly increase inflammatory responses associated with multiple chronic diseases. We investigated the effects of long-term exposure to ambient air pollution on high-sensitivity C-reactive protein (hs-CRP) using data from 60,581 participants enrolled in the Korean Genome and Epidemiology Study-Health Examinees Study between 2012 and 2017. Community Multiscale Air Quality System with surface data assimilation was used to estimate the participants' exposure to criteria air pollutants based on geocoded residential addresses. Long-term exposure was defined as the 2-year moving average concentrations of PM10, PM2.5, SO2, NO2, and O3. Multivariable linear and logistic regression models were utilized to estimate the percent changes in hs-CRP and odds ratios of systemic low-grade inflammation (hs-CRP > 3 mg/L) per interquartile range increment in air pollutants. We identified positive associations between hs-CRP and PM10 (% changes: 3.75 [95% CI 2.68, 4.82]), PM2.5 (3.68, [2.57, 4.81]), SO2 (1.79, [1.10, 2.48]), and NO2 (3.31, [2.12, 4.52]), while negative association was demonstrated for O3 (-3.81, [-4.96, -2.65]). Elevated risks of low-grade inflammation were associated with PM10 (odds ratio: 1.07 [95% CI 1.01, 1.13]), PM2.5 (1.08 [1.02, 1.14]), and SO2 (1.05 [1.01, 1.08]). The odds ratios reported indicated that the exposures might be risk factors for inflammatory conditions; however, they did not reflect strong associations. Our findings suggest that exposure to air pollutants may play a role in the inflammation process.

Association between haemoglobin A1c and all-cause and cause-specific mortality in middle-aged and older Koreans: a prospective cohort study.

BACKGROUND: This study aimed to examine associations between haemoglobin A1c (HbA1c) levels over time and all-cause and cause-specific mortality in middle-aged and older Koreans. METHODS: Using 16 years of follow-up data from the Korean Genome and Epidemiology Study, we analysed 9294 individuals aged 40-69 years with no history of cardiovascular disease (CVD) or cancer. Participants were divided into a known diabetes group and five groups categorized by HbA1c levels (< 5.0%, 5.0-5.4%, 5.5-5.9%, 6.0-6.4%, and ≥ 6.5%). Hazard ratios (HRs) for all-cause and cause-specific mortality associated with HbA1c levels were calculated using a conventional and a time-dependent Cox proportional hazards model. Restricted cubic spline models were fitted to investigate the relationship between continuous HbA1c levels and mortality among people without known diabetes. Subgroup analyses were performed for age, sex, smoking, hypertension, liver diseases, and red blood cell counts. RESULTS: During a median follow-up period of 15.7 years, there were 944 deaths, including 185 deaths from CVD, 359 from cancer, and 125 from all external causes. Compared with participants with HbA1c levels of 5.5-5.9%, multivariate-adjusted HRs and 95% confidence intervals for all-cause death of participants with levels < 5.0%, 5.0-5.4%, 6.0-6.4%, and ≥ 6.5% and participants with known diabetes were 1.84 (1.35-2.51), 1.13 (0.95-1.34), 1.30 (1.04-1.62), 1.37 (0.97-1.93), and 2.03 (1.70-2.44), respectively. The risk of cancer mortality was significantly increased in HbA1c < 5.0% (HR, 2.21; 95% CI 1.42-3.44) and known diabetes (HR, 1.60; 95% CI 1.18-2.15). When we performed diverse subgroup analyses, low HbA1c levels at baseline were strongly associated with mortality in participants with liver diseases. CONCLUSIONS: We found U-shaped associations between HbA1c levels at baseline and over time and all-cause mortality in middle-aged and older Koreans. Additionally, the risk of cancer mortality increased both in low and high HbA1c groups, but CVD mortality increased only in high HbA1c group. In particular, people with liver diseases and low HbA1c levels had a high risk of all-cause mortality. Therefore, more careful management of these groups is suggested to identify any deteriorating health conditions.

A Method to Investigate the Helicobacter pylori-Associated DNA Methylome.

The protocol described here for methylome profiling consists of two parts. One is the experimental part for a genome-wide analysis of methylation level, and the other is the bioinformatics analysis of the methylome data. DNA methylation measurement is conducted using the commercially available array-based "Infinium Human Methylation 450K BeadChip" kit (or its updated version, Infinium MethylationEPICBeadChip). This BeadChip allows the high-throughput DNA methylation analysis suitable for genome-wide studies with large sample size. The results give intensities of the beads providing information on the unmethylated and methylated CpG sites. Bioinformatics data analysis involves reading the intensities as methylation values using R packages. Here, we provide a detailed analysis tool for each of the data analysis steps.

Dietary mercury intake and colorectal cancer risk: A case-control study.

BACKGROUND & AIMS: The main source of mercury exposure is food such as fish and shellfish. Mercury is a growing concern due to its associations with a number of harmful health effects, including cancer. The objectives of this study were to examine the association between dietary mercury intake and colorectal cancer (CRC) risk and to determine whether this association differs by anatomical site and menopausal status. METHODS: A case-control study was conducted with 2769 participants (923 cases and 1846 controls) in Korea. Dietary mercury intake and fish and shellfish consumption were assessed using a semiquantitative food frequency questionnaire. RESULTS: A high intake of dietary mercury was associated with an increased risk of CRC (in the group with lower fish and shellfish consumption; odds ratio (OR): 3.13; 95% confidence interval (95% CI): 2.33, 4.71, in the group with higher fish and shellfish intake; OR: 3.84, 95% CI: 2.20, 7.30) after adjusting for all potential confounders by anatomic site in men. Among women, the results differed by fish and shellfish consumption and menopausal status. Regarding the amount of fish and shellfish intake, a positive association was found only in the group with lower intake (CRC; OR: 2.24, 95% CI: 1.36, 3.72, colon cancer; OR: 2.25, 95% CI: 1.22, 4.16, rectal cancer; OR: 2.28, 95% CI: 1.13, 4.57). In the stratified analysis by menopausal status, the elevated risk of CRC was still observed among both pre- and postmenopausal women depending on anatomical site, except for the colon cancer patients with premenopausal status. CONCLUSIONS: A high intake of mercury was associated with an elevated risk of overall CRC. Future large-scale prospective cohort studies are recommended to investigate the causal effects of dietary mercury intake by fish and shellfish consumption on CRC risk depending on anatomical site and menopausal status.

Identification of Dietary Patterns Associated with Incidence of Hyperglycemia in Middle-Aged and Older Korean Adults.

Little is known about the association between dietary patterns and hyperglycemia incidence among Korean adults. Hence, we aimed to prospectively investigate the major dietary patterns associated with hyperglycemia among middle-aged and older Korean adults. In total, 55,457 adults (18,292 men and 37,165 women) aged 40 to 79 years, who were previously enrolled in the Health Examinee Study of the Korean Genome and Epidemiology Study and had no history of type 2 diabetes mellitus (T2DM) or cancer at baseline, were included. Dietary patterns were identified by a factor analysis based on dietary data, which were assessed at baseline using a validated food-frequency questionnaire. Participants were classified as having hyperglycemia if fasting blood glucose levels were ≥126 mg/dL or physician diagnosed T2DM during follow-up. Multivariable Cox proportional hazard models were used to examine the associations between each dietary pattern and future hyperglycemia risk after adjusting for potential confounders. After a mean follow-up of 4.9 years, 2574 new cases of hyperglycemia were identified. Using a factor analysis, four distinct dietary patterns were identified: "prudent;" "fatty fish, meat, and flour-based food;" "coffee and sweets;" and "whole grain (men)" or "white rice (women)." The "prudent" pattern was inversely associated with hyperglycemia risk only in women (hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.63-0.89; p for trend = 0.0003). Conversely, women in the highest quintile of the "fatty fish, meat, and flour-based food" pattern showed an increased risk of hyperglycemia (HR, 1.22; 95% CI, 1.03-1.44; p for trend = 0.0210) compared with those in the lowest quintile. The "coffee and sweets" and "white rice" patterns were not associated with hyperglycemia risk in women. The dietary patterns observed in men had no associations with hyperglycemia incidence. Our findings suggest that a diet rich in vegetables, mushrooms, seaweeds, fruits, and soy products and low in fatty fish and high-fat meat may potentially play a protective role in T2DM development with sex differences in middle-aged and older Korean adults.

Association between dietary cadmium intake and early gastric cancer risk in a Korean population: a case-control study.

PURPOSE: Foods such as grains and vegetables are the dominant sources of exposure to cadmium, which has been classified as a carcinogen by various public health agencies. Cadmium exposure is a growing concern due to its associations with numerous harmful health effects, including gastric cancer risk. The objective of this study was to investigate the association of dietary cadmium intake and the consumption of cadmium-contributing foods with early gastric cancer risk. METHODS: A case-control study including 1245 subjects (cases, 415; controls, 830) was conducted in Korea. The dietary cadmium intake and the consumption of cadmium-contributing foods were assessed using a semi-quantitative food frequency questionnaire. RESULTS: After adjustment for covariates, the gastric cancer risk was increased for participants in the highest tertile of cadmium intake [odds ratios (ORs) 1.33, 95% confidence intervals (95% CIs) 0.94-1.88], but there was no significance. Both female (ORs 2.71, 95% CIs 1.37-5.36) and male (ORs 1.63, 95% CIs 1.07-2.50) participants in the highest tertile of rice consumption had a higher gastric cancer risk than did those in the lowest tertile. Men in the highest tertile of crab consumption had a gastric cancer risk 2.23 times greater than that of men in the lowest tertile (ORs 2.23, 95% CIs 1.21-4.13), but a difference was not seen in women. CONCLUSIONS: Future studies examining the causal effects of dietary cadmium intake and the consumption of cadmium-contributing foods on early gastric cancer risk in large-scale prospective cohorts are recommended.

LINE-1 hypomethylation is associated with radiation-induced genomic instability in industrial radiographers.

Global DNA hypomethylation is proposed as a potential biomarker for cancer risk associated with genomic instability, which is an important factor in radiation-induced cancer. However, the associations among radiation exposure, changes in DNA methylation, and carcinogenesis are unclear. The aims of this study were (1) to examine whether low-level occupational radiation exposure induces genomic DNA hypomethylation; and (2) to determine the relationships between radiation exposure, genomic DNA hypomethylation and radiation-induced genomic instability (RIGI) in industrial radiographers. Genomic DNA methylation levels were measured in blood DNA from 40 radiographers and 28 controls using the LINE-1 pyrosequencing assay and the luminometric methylation assay. Further, the micronucleus-centromere assay was performed to measure aneuploidy of chromosomes 1 and 4 as a marker of delayed RIGI. Genomic DNA methylation levels were significantly lower in radiographers than those in controls. LINE-1 hypomethylation was not significantly correlated with recent 1-year, recent 3-year, or total cumulative radiation doses in radiographers; however, LINE-1 hypomethylation significantly correlated with the cumulative radiation dose without recent 3-year exposure data (D3dose, r = -0.39, P < 0.05). In addition, LINE-1 hypomethylation was a significant contributor to aneuploidy frequency by D3dose (F (2, 34) = 13.85, P < 0.001), in which a total of 45% of the variance in aneuploidy frequency was explained. Our results provide suggestive evidence regarding the delayed effects of low-dose occupational radiation exposure in radiographers and its association with LINE-1 hypomethylation; however, additional studies using more subjects are needed to fully understand the relationship between genomic DNA hypomethylation and RIGI. Environ. Mol. Mutagen. 60: 174-184, 2019. © 2018 Wiley Periodicals, Inc.

Genome-Wide Association of Genetic Variation in the PSCA Gene with Gastric Cancer Susceptibility in a Korean Population.

PURPOSE: Half of the world's gastric cancer cases and the highest gastric cancer mortality rates are observed in Eastern Asia. Although several genome-wide association studies (GWASs) have revealed susceptibility genes associated with gastric cancer, no GWASs have been conducted in the Korean population, which has the highest incidence of gastric cancer. MATERIALS AND METHODS: We performed genome scanning of 450 gastric cancer cases and 1,134 controls via Affymetrix Axiom Exome 319 arrays, followed by replication of 803 gastric cancer cases and 3,693 healthy controls. RESULTS: We showed that the rs2976394 in the prostate stem cell antigen (PSCA) gene is a gastriccancer-susceptibility gene in a Korean population, with genome-wide significance and an odds ratio (OR) of 0.70 (95% confidence interval [CI], 0.64 to 0.77). A strong linkage disequilibrium with rs2294008 was also found, indicating an association with susceptibility. Individuals with the CC genotype of the PSCA gene showed an approximately 2-fold lower risk of gastric cancer compared to those with the TT genotype (OR, 0.47; 95% CI, 0.39 to 0.57). The effect of the PSCA gene on gastric cancer was more prominent in the female population and for diffuse type gastric cancer. CONCLUSION: Our result confirmed that the PSCA gene may be the most important susceptibility gene for gastric cancer risk in a Korean population.

Genome-wide profiling of normal gastric mucosa identifies Helicobacter pylori- and cancer-associated DNA methylome changes.

The large geographic variations in the incidence of gastric cancer (GC) are likely due to differential environmental exposures, in particular to Helicobacter pylori (H. pylori) infection. We aimed to investigate the impact of H. pylori on the epigenome in normal gastric mucosa and methylation changes associated with cancer risk independent of H. pylori. A discovery set of normal gastric mucosa from GC cases (n = 42) and controls (n = 42), nested in a large case-control study and stratified by H. pylori status, were subjected to genome-wide methylation profiling. Single-nucleotide polymorphism arrays from peripheral blood leukocytes were used to conduct methylation quantitative trait loci (mQTL) analysis. A validation set of gastric mucosa samples (n = 180) was used in the replication phase. We found 1,924 differentially methylated positions (DMPs) and 438 differentially methylated regions (DMRs) associated with H. pylori infection, most of which were hypermethylated. Significant methylation alterations identified in the initial set were successfully replicated. Furthermore, the H. pylori-associated DMP/Rs showed marked stability ('epigenetic memory') after H. pylori clearance. Interestingly, we found 152 DMRs associated with cancer risk independent of the H. pylori status in normal gastric mucosa. The methylation score derived from three biomarkers was a strong predictor of GC. Finally, the mQTL analysis indicated that the H. pylori- and cancer-specific methylation signatures were minimally affected by genetic variation. The comprehensively characterized methylome changes associated with H. pylori infection and GC risk in our study might serve as potential biomarkers for early cancer progression in tumour-free gastric mucosa.

Lowly methylated region analysis identifies EBF1 as a potential epigenetic modifier in breast cancer.

Breast cancer (BC) encompasses heterogeneous pathologies with different subtypes exhibiting distinct molecular changes, including those related to DNA methylation. However, the role of these changes in mediating BC heterogeneity is poorly understood. Lowly methylated regions (LMRs), non-CpG island loci that usually contain transcription factor (TF) binding sites, have been suggested to act as regulatory elements that define cellular identity. In this study, we aimed to identify the key subtype-specific TFs that may lead to LMR generation and shape the BC methylome and transcription program. We initially used whole-genome bisulfite sequencing (WGBS) data available at The Cancer Genome Atlas (TCGA) portal to identify subtype-specific LMRs. Differentially methylated regions (DMRs) within the BC PAM50 subtype-specific LMRs were selected by comparing tumors and normal tissues in a larger TCGA cohort assessed by HumanMethylation450 BeadChip (450K) arrays and TF enrichment analyses were performed. To assess the impact of LMRs on gene expression, TCGA RNA sequencing data were downloaded and Pearson correlations between methylation levels of loci presenting subtype-specific TF motifs and expression of the nearest genes were calculated. WGBS methylome data revealed a large number of LMRs for each of the BC subtypes. Analysis of these LMRs in the 450K datasets available for a larger sample set identified 7,765, 5,657, and 19 differentially methylated positions (DMPs) between normal adjacent tissues and tumor tissues from basal, luminal, and HER2-enriched subtypes, respectively. Unsupervised clustering showed that the discriminatory power of the top DMPs was remarkably strong for basal BC. Interestingly, in this particular subtype, we found 4,409 differentially hypomethylated positions grouped into 1,185 DMRs with a strong enrichment for the early B-cell factor 1 (EBF1) motifs. The methylation levels of the DMRs containing EBF1 motifs showed a strong negative correlation with the expression of 719 nearby genes, including BTS2 and CD74, two oncogenes known to be specific for basal BC subtype and for poor outcome. This study identifies LMRs specific to the three main BC subtypes and reveals EBF1 as a potentially important regulator of BC subtype-specific methylation and gene expression program.

Blood lead concentrations and attention deficit hyperactivity disorder in Korean children: a hospital-based case control study.

BACKGROUND: Because the developing brain of a child is vulnerable to environmental toxins, even very low concentration of neurotoxin can affect children's neurodevelopment. Lead is a neurotoxic heavy metal which has the harmful effect on the striatal-frontal circuit of brain. This area of the brain is known to be closely related to attention deficit hyperactivity disorder (ADHD) pathophysiology. The primary objective of the present study was to investigate whether elevated blood lead concentration is a risk factor for ADHD. The secondary objective was to examine the association between blood lead concentration and symptom severity. METHODS: We conducted a frequency-matched, hospital-based case-control study with 114 medically diagnosed ADHD cases and 114 controls. The participants were matched for age and sex. The diagnoses of ADHD were assessed with semi-structured diagnostic interviews. The participants completed the continuous performance test (CPT), and their parents completed the ADHD-rating scale (ADHD-RS). Blood lead concentrations were measured by using graphite furnace atomic absorption spectrometry featuring Zeeman background correction. RESULTS: Children with ADHD exhibited blood lead concentrations that were significantly higher than those of the controls ( 1.90 ± 086 µg/dℓ vs. 1.59 ± 0.68 µg/dℓ, p = 0.003). The log transformed total blood lead concentration was associated with a higher risk of ADHD (OR: 1.60, 95 % CI: 1.04-2.45, p < 0.05). The analysis also revealed that the children with blood lead concentrations above 2.30 µg/dℓ were at a 2.5-fold (95 % CI: 1.09-5.87, p < 0.05) greater risk of having ADHD. After adjusting for covariates, our multivariate regression models indicated that blood lead concentrations were not significantly associated with ADHD-RS or CPT profiles among the ADHD cases. CONCLUSION: Even low blood lead concentrations are a risk factor for ADHD in children. This study warrants primary prevention policies to reduce the environmental lead burden. Future studies may be required to ascertain the effects of lead on symptom severity in ADHD.

Protective Effect of Onion Extract on Bleomycin-Induced Cytotoxicity and Genotoxicity in Human Lymphocytes.

Following one of the world's largest nuclear accidents, occured at Fukushima, Japan in 2011, a significant scientific effort has focused on minimizing the potential adverse health effects due to radiation exposure. The use of natural dietary antioxidants to reduce the risk of radiation-induced oxidative DNA damage is a simple strategy for minimizing radiation-related cancer rates and improving overall health. The onion is among the richest sources of dietary flavonoids and is an important food for increasing their overall intake. Therefore, we examined the effect of an onion extract on cyto- and geno-toxicity in human lymphocytes treated with bleomycin (BLM), a radiomimetic agent. In addition, we measured the frequency of micronuclei (MN) and DNA damage following treatment with BLM using a cytokinesis-blocked micronucleus assay and a single cell gel electrophoresis assay. We observed a significant increase in cell viability in lymphocytes treated with onion extract then exposed to BLM compared to cells treated with BLM alone. The frequency of BLM induced MN and DNA damage increased in a dose-dependent manner; however, when lymphocytes were pretreated with onion extract (10 and 20 µL/mL), the frequency of BLM-induced MN was decreased at all doses of BLM and DNA damage was decreased at 3 µg/mL of BLM. These results suggest that onion extract may have protective effects against BLM-induced cyto- and genotoxicity in human lymphocytes.

Dietary folate, one-carbon metabolism-related genes, and gastric cancer risk in Korea.

SCOPE: We evaluated the interactions between polymorphisms involved in one-carbon metabolism-related genes and dietary folate intake in gastric cancer risk within the Korean population through a hospital-based case-control study. METHODS AND RESULTS: A total of 542 controls and 271 cases were included. Genotype data were selected from data produced by the Affymetrix Axiom(®) Exome 319 Array. We considered seven single nucleotide polymorphisms (SNPs) of five genes whose SNPs are located in the coding region with a minor allele frequency > 5%: MTHFR (G1793A, A1298C, C677T), MTR A2756G, MTRR A66G, SHMT1 C1420T, and SLC19A1 G80A. Our study found that MTR A2756G was associated with a decreased gastric cancer risk. MTHFR G1793A showed a statistically significant interaction between dietary folate intake and gastric cancer. CONCLUSION: Our results suggest that MTR A2756G is significantly associated with gastric cancer risk, and that MTHFR G1793A statistically interacts with dietary folate intake. Our findings indicate that gene-folate interactions may contribute to gastric cancer risk.

Delayed Numerical Chromosome Aberrations in Human Fibroblasts by Low Dose of Radiation.

Radiation-induced genomic instability refers to a type of damage transmitted over many generations following irradiation. This delayed impact of radiation exposure may pose a high risk to human health and increases concern over the dose limit of radiation exposure for both the public and radiation workers. Therefore, the development of additional biomarkers is still needed for the detection of delayed responses following low doses of radiation exposure. In this study, we examined the effect of X-irradiation on delayed induction of numerical chromosomal aberrations in normal human fibroblasts irradiated with 20, 50 and 100 cGy of X-rays using the micronucleus-centromere assay. Frequencies of centromere negative- and positive-micronuclei, and aneuploidy of chromosome 1 and 4 were analyzed in the surviving cells at 28, 88 and 240 h after X-irradiation. X-irradiation increased the frequency of micronuclei (MN) in a dose-dependent manner in the cells at all measured time-points, but no significant differences in MN frequency among cell passages were observed. Aneuploid frequency of chromosomes 1 and 4 increased with radiation doses, and a significantly higher frequency of aneuploidy was observed in the surviving cells analyzed at 240 h compared to 28 h. These results indicate that low-dose of X-irradiation can induce delayed aneuploidy of chromosomes 1 and 4 in normal fibroblasts.

Association between preoperative C-reactive protein level and colorectal cancer survival: a meta-analysis.

PURPOSE: C-reactive protein (CRP) is widely known as a major nonspecific systemic inflammatory marker. A number of previous studies have suggested that elevated preoperative CRP is associated with poor prognosis in colorectal cancer. We aimed to explore the effects of preoperative CRP on colorectal cancer survival through a meta-analysis. METHODS: A total of 21 studies, including a total of 3934 colorectal cancer patients, were eligible. The multivariate-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of selected studies were used to assess the summary estimates of the association between preoperative CRP and colorectal cancer survival. RESULTS: The pooled HRs of elevated preoperative CRP for earlier stage patients were 2.04 (95% CI 1.45-2.86) for OS, 4.37 (95% CI 2.63-7.27) for CSS, and 1.88 (95% CI 0.97-3.67) for DFS. The pooled HRs of a higher Glasgow Prognostic Score (GPS)/modified GPS (mGPS) for earlier stage patients were 2.20 (95% CI 1.61-3.02) for OS and 1.80 (95% CI 1.37-2.37) for CSS. The association between elevated preoperative CRP and poor survival was observed in patients with advanced cancer. Elevated CRP and GPS/mGPS were significantly associated with poor survival. CONCLUSION: Preoperative CRP and its related markers, GPS and mGPS, were significantly associated with the survival of colorectal cancer surgery patients. The HRs of GPS and mGPS were highly homogeneous across studies for all survival types. Thus, GPS and mGPS may serve as stable predictors of the survival of colorectal cancer surgery patients.

Estimation of the Biological Half-Life of Methylmercury Using a Population Toxicokinetic Model.

Methylmercury is well known for causing adverse health effects in the brain and nervous system. Estimating the elimination constant derived from the biological half-life of methylmercury in the blood or hair is an important part of calculating guidelines for methylmercury intake. Thus, this study was conducted to estimate the biological half-life of methylmercury in Korean adults. We used a one-compartment model with a direct relationship between methylmercury concentrations in the blood and daily dietary intake of methylmercury. We quantified the between-person variability of the methylmercury half-life in the population, and informative priors were used to estimate the parameters in the model. The population half-life of methylmercury was estimated to be 80.2 ± 8.6 days. The population mean of the methylmercury half-life was 81.6 ± 8.4 days for men and 78.9 ± 8.6 days for women. The standard deviation of the half-life was estimated at 25.0 ± 8.6 days. Using the direct relationship between methylmercury concentrations in blood and methylmercury intake, the biological half-life in this study was estimated to be longer than indicated by the earlier studies that have been used to set guideline values.

Dietary Patterns and Risk for Metabolic Syndrome in Korean Women: A Cross-Sectional Study.

Dietary patterns are a risk factor for metabolic syndrome (MetS). The prevalence of MetS has increased in Korea, and this condition has become a public health issue. Therefore, the present cross-sectional study aimed to identify the associations between dietary patterns and the risk of MetS among Korean women.The data of 5189 participants were analyzed to determine dietary intake and lifestyle. A principal components analysis was employed to determine participant dietary patterns with regard to 106 food items. MetS was diagnosed using the National Cholesterol Education Program, Adult Treatment Panel III. Logistic regression analyses were applied to evaluate the associations between dietary pattern quintiles and MetS and to generate odds ratios (ORs) and 95% confidence intervals (CIs) after adjusting for potential confounders.Three dietary patterns were identified: "traditional," "western," and "prudent." The "prudent" dietary pattern consisted of a high intake of fruits and fruit products as well as nuts, dairy, and a low consumption of grains; this pattern was negatively associated with the risk of MetS. The highest quintile of the "prudent" dietary pattern was significantly less likely to develop MetS (OR: 0.5, 95% CI: 0.36-0.68, P for trend <0.001) compared with the lowest quintile. This pattern was also negatively associated with all of the MetS diagnostic criteria: abdominal obesity (OR: 0.52, 95% CI: 0.41-0.65), blood pressure (OR: 0.72, 95% CI: 0.59-0.87), triglycerides (OR: 0.67, 95% CI: 0.52-0.85), fasting glucose (OR: 0.64, 95% CI: 0.43-0.95), and high-density lipoprotein cholesterol (OR: 0.53, 95% CI: 0.42-0.68). However, the "traditional" and "western" dietary patterns were not associated with the risk of MetS.The "prudent" dietary pattern was negatively associated with the risk of developing MetS among Korean women.

The Association of LINE-1 Hypomethylation with Age and Centromere Positive Micronuclei in Human Lymphocytes.

Global hypomethylation in white blood cell (WBC) DNA has recently been proposed as a potential biomarker for determining cancer risk through genomic instability. However, the amplitude of the changes associated with age and the impacts of environmental factors on DNA methylation are unclear. In this study, we investigated the association of genomic hypomethylation with age, cigarette use, drinking status and the presence of centromere positive micronuclei (MNC+)-a biomarker for age-dependent genomic instability. Genomic hypomethylation of the repetitive element LINE-1 was measured in WBC DNA from 32 healthy male volunteers using the pyrosequencing assay. We also measured MNC+ with the micronucleus-centromere assay using a pan-centromeric probe. Possibly due to the small sample size and resulting low statistical power, smoking and drinking status had no significant effect on LINE-1 hypomethylation or the occurrence of MNC+. Consequently, we did not include them in further analyses. In contrast, LINE-1 hypomethylation and age significantly predicted MNC+; therefore, we examined whether LINE-1 hypomethylation plays a role in MNC+ formation by age, since genomic hypomethylation is associated with genomic instability. However, LINE-1 hypomethylation did not significantly mediate the effect of age on MNC+. Our data indicate that the repetitive element LINE-1 is demethylated with age and increasing MNC+ frequency, but additional studies are needed to fully understand the relation between genomic DNA hypomethylation, age and genomic instability.