Long-term exposure to ozone and sulfur dioxide increases the incidence of type 2 diabetes mellitus among aged 30 to 50 adult population.

AIMS/HYPOTHESIS: Worldwide, the information regarding the associations between long-term exposure to ozone (O3) and sulfur dioxide (SO2) and the development of type 2 diabetes remains scarce, especially in Asia. This study aimed to investigate the long-term effects of exposure to ambient O3 and SO2 on the incidence of type 2 diabetes with consideration of other air pollutants in Taiwanese adults aged 30 to 50 years. METHODS: A total of 6,426,802 non-diabetic participants aged between 30 and 50 years old were obtained from the National Health Insurance Research Database between 2005 and 2016. Incident type 2 diabetes was the main diagnosis at medical visits. Air quality data were provided by the Taiwan Environmental Protection Administration. The air pollutant concentrations for each participant were estimated using the ordinary kriging method to interpolate daily concentrations of O3, SO2, carbon monoxide (CO), nitrogen dioxide (NO2), suspended fine particles (with an aerodynamic diameter less than 2.5 µm; PM2.5), and suspended particles (with an aerodynamic diameter less than 10 µm; PM10) in residential districts across Taiwan. Six-year average concentrations of pollutants were calculated from January 1, 2005 to December 31, 2010, and data were categorized into quartiles. We performed Cox regression models to analyze the long-term effects of exposure to O3 and SO2 on the incidence of type 2 diabetes. RESULTS: The hazard ratio (HR) for the incidence of diabetes per each interquartile range (IQR) increase in ozone exposure (3.30 ppb) was 1.058 (95% confidence interval (CI): 1.053, 1.064) and 1.011 (95% CI: 1.007, 1.015) for SO2 exposure (1.77 ppb) after adjusting for age, sex, socioeconomic status, urbanization level, temperature, humidity, and chronic comorbidities (Model 3). Furthermore, for every 3.30 ppb increase of O3, the HR for incident type 2 diabetes was 1.093 (95% CI: 1.087, 1.100) after controlling factors shown in Model 3 plus SO2 and PM2.5. On the other hand, for every 1.77 ppb increase of SO2, the HR for incident type 2 diabetes was 1.073 (95% CI: 1.068, 1.079) after controlling factors shown in Model 3 plus NO2 and PM2.5. CONCLUSIONS: Long-term exposure to ambient O3 and SO2 was associated with a higher risk of developing type 2 diabetes for Taiwanese population. Exposure to O3 and SO2 may play a role in the adult early-onset type 2 diabetes.

A predictive model for identifying low medication adherence among older adults with hypertension: A classification and regression tree model.

Various individual characteristics may affect medication adherence; however, few studies have investigated the effect of interrelationships among these various individual characteristics on medication adherence. This cross-sectional study explored the interrelationships among risk factors for medication adherence and established a predictive model of low medication adherence among older adults with hypertension. Convenience sampling was used to recruit 300 older adults with hypertension. The following parameters were recorded: demographic and disease characteristics, health beliefs, self-efficacy, social support, and medication adherence of antihypertensive drugs. Classification and regression tree (CART) analysis was performed to develop a predictive model of low medication adherence. The CART model revealed that health belief, disease duration, self-efficacy, and social support interacted to contribute to various pathways of low medication adherence. The predicted accuracy of the model was validated with a low misclassification rate of 26%. The proposed classification model can help identify risk cases with low medication adherence. Suitable health education programs based on these risk factors to manage and improve medication adherence for older adults with hypertension could be considered.

Combined effect of polymorphisms of MTHFR and MTR and arsenic methylation capacity on developmental delay in preschool children in Taiwan.

Polymorphisms of methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MTR) are related to cognitive dysfunction and mental disability. These genes, along with folate and vitamin B12 levels, are regulators of one-carbon metabolism, which synthesizes S-adenosylmethionine (SAM) as a methyl donor for arsenic methylation. The aim of this study was to explore whether polymorphisms of MTHFR and MTR influence arsenic methylation capacity and plasma folate and vitamin B12 levels and if these influences cause developmental delay in preschool children. A total of 178 children with developmental delay and 88 without developmental delay were recruited from August 2010 to March 2014. A high-performance liquid chromatography-hydride generator and atomic absorption spectrometer were used to determine urinary arsenic species. Plasma folate and vitamin B12 concentrations were measured by SimulTRAC-SNB radioassay. Polymorphisms of MTHFR C677T, MTHFR A1298C, and MTR A2756G were examined by polymerase chain reaction and restriction fragment length variation. The results show that MTHFR C677T C/T and T/T genotypes had a lower risk of developmental delay than the C/C genotype (odds ratio [OR] = 0.47; 95% confidence interval, 0.26-0.85). Subjects with the MTHFR C677T C/C genotype had significantly lower plasma folate and vitamin B12 levels than those with the MTHFR C677T C/T and T/T genotype. The MTHFR C677T C/C genotype combined with high total urinary arsenic and poor arsenic methylation capacity indices significantly increased the OR of developmental delay in a dose-response manner. This is the first study to show the combined effect of MTHFR C677T genotype and poor arsenic methylation capacity on developmental delay.

Plasma selenium influences arsenic methylation capacity and developmental delays in preschool children in Taiwan.

Inefficient arsenic methylation capacity has been associated with developmental delay in preschool children. Selenium has antioxidant and anti-inflammatory properties that protect experimental animals from chemically induced neurotoxicity. The present study was designed to explore whether plasma selenium levels affects arsenic methylation capacity related to developmental delay in preschool children. A case-control study was conducted from August 2010 to March 2014. All participants were recruited from the Shin Kong Wu Ho-Su Memorial Teaching Hospital. In total, 178 children with a developmental delay and 88 children without a delay were recruited. High-performance liquid chromatography-linked hydride generator and atomic absorption spectrometry were used to determine urinary arsenic species, including arsenite (AsIII), arsenate (AsV), monomethylarsonic acid (MMAV), and dimethylarsinic acid (DMAV). Plasma selenium levels were measured by inductively coupled plasma mass spectrometry. As results, plasma selenium concentration was significantly inversely associated with the odds ratio (OR) of developmental delay. Plasma selenium concentration was positively associated with arsenic methylation capacity [percentage of inorganic arsenic and percentage of MMAV (MMAV%) decreased, and percentage of DMAV (DMAV%) increased]. High plasma selenium concentration and high DMA% significantly and additively interacted to decrease the OR of developmental delay; the OR and 95% confidence interval were 0.40 (0.18-0.90). This is the first study to show a combined dose-response effect of plasma selenium concentration and that efficient arsenic methylation capacity decreased the OR of developmental delay in preschool children.

Association of plasma folate, vitamin B12 levels, and arsenic methylation capacity with developmental delay in preschool children in Taiwan.

Developmental delay has been associated with inefficient arsenic methylation capacity in preschool children. Folate and vitamin B12 are important nutrients that produce s-adenosylmethionine during single-carbon metabolism and provide methyl groups for arsenic methylation. The aim of the present study was to explore whether plasma folate and vitamin B12 levels influence arsenic methylation capacity and in turn are related to developmental delay in preschool children. A case-control study was conducted in 178 children with developmental delay and 88 normal children, who were recruited from Shin Kong Wu Ho-Su Memorial Teaching Hospital from August 2010 to March 2014. Arsenite (AsIII), arsenate (AsV), monomethylarsonic acid (MMAV), and dimethylarsinic acid (DMAV) in the urine was determined by high-performance liquid chromatography-linked hydride generator and atomic absorption spectrometry. Plasma folate and vitamin B12 levels were measured using a SimulTRAC-SNB radioassay. The results show that the combination of high plasma folate and high vitamin B12 levels were correlated with efficient arsenic methylation capacity (low MMAV %, low InAs %, and high DMAV %). High MMAV % significantly increased and high DMAV % and secondary methylation index decreased the odds ratio (OR) of developmental delay in a dose-dependent manner in both low plasma folate and low vitamin B12 (low/low) groups; the multivariate OR and 95% confidence interval were 5.01 (0.83-30.06), 0.21 (0.04-1.23), and 0.20 (0.03-1.20), respectively. This is the first study to show that the combination of high plasma folate and high vitamin B12 levels increases arsenic methylation capacity and indirectly decreases the OR of developmental delay in preschool children.

Adiponectin gene polymorphisms and obesity increase the susceptibility to arsenic-related renal cell carcinoma.

Our recent study found that high urinary total arsenic levels were associated with renal cell carcinoma (RCC). Recent studies demonstrated that low circulating adiponectin was related to RCC. The aim of the present study was to explore the relationship between adiponectin gene (ADIPOQ) polymorphisms and RCC and investigate whether individuals with an ADIPOQ risk genotype, obesity, and high urinary total arsenic levels have a modified odds ratio (OR) of RCC. A total of 389 RCC patients and 389 age- and sex-matched controls were recruited between November 2006 and December 2012 in Taiwan. Image-guided biopsy or surgical resection of renal tumors was performed to pathologically verify RCC. Genomic DNA was used to examine the genotypes of the ADIPOQ rs182052, ADIPOQ rs2241766, ADIPOQ rs1501299, and ADIPOQ rs1063539 SNPs by PCR-RFLP. HPLC-HG-AAS was used to measure the concentrations of urinary arsenic species. Participants with the ADIPOQ rs182052 G/A+A/A genotype had a significantly higher OR of RCC compared with those with the ADIPOQ rs182052 G/G genotype. The OR (95% confidence interval [CI]) was 1.70 (1.23-2.36). The OR of RCC for the combined effect of high urinary total arsenic levels and obesity, which was dose-dependent, in individuals with the ADIPOQ rs182052 G/A+A/A genotype was 9.33 (3.85-22.62). The present study found significant combined effects of obesity and the ADIPOQ rs182052 G/A+A/A genotype on the arsenic-related risk of RCC in a population with low arsenic exposure. Arsenic exposure, obesity, and the ADIPOQ rs182052 polymorphism could be predictors of a higher OR of RCC.

Inadequate dietary energy intake associates with higher prevalence of metabolic syndrome in different groups of hemodialysis patients: a clinical observational study in multiple dialysis centers.

BACKGROUND: Metabolic syndrome (MetS) has been established as a risk for cardiovascular diseases and mortality in hemodialysis patients. Energy intake (EI) is an important nutritional therapy for preventing MetS. We examined the association of self-reported dietary EI with metabolic abnormalities and MetS among hemodialysis patients. METHODS: A cross-sectional study design was carried out from September 2013 to April 2017 in seven hemodialysis centers. Data were collected from 228 hemodialysis patients with acceptable EI report, 20 years old and above, underwent three hemodialysis sessions a week for at least past 3 months. Dietary EI was evaluated by a three-day dietary record, and confirmed by 24-h dietary recall. Body compositions were measured by bioelectrical impedance analysis. Biochemical data were analyzed using standard laboratory tests. The cut-off values of daily EI were 30 kcal/kg, and 35 kcal/kg for age ≥ 60 years and < 60 years, respectively. MetS was defined by the American Association of Clinical Endocrinologists (AACE-MetS), and Harmonizing Metabolic Syndrome (HMetS). Logistic regression models were utilized for examining the association between EI and MetS. Age, gender, physical activity, hemodialysis vintage, Charlson comorbidity index, high sensitive C-reactive protein, and interdialytic weight gains were adjusted in the multivariate analysis. RESULTS: The prevalence of inadequate EI, AACE-MetS, and HMetS were 60.5%, 63.2%, and 53.9%, respectively. Inadequate EI was related to higher proportion of metabolic abnormalities and MetS (p <  0.05). Results of the multivariate analysis shows that inadequate EI was significantly linked with higher prevalence of impaired fasting glucose (OR = 2.42, p <  0.01), overweight/obese (OR = 6.70, p <  0.001), elevated waist circumference (OR = 8.17, p <  0.001), AACE-MetS (OR = 2.26, p <  0.01), and HMetS (OR = 3.52, p <  0.01). In subgroup anslysis, inadequate EI strongly associated with AACE-MetS in groups of non-hypertension (OR = 4.09, p = 0.004), and non-cardiovascular diseases (OR = 2.59, p = 0.012), and with HMetS in all sub-groups of hypertension (OR = 2.59~ 5.33, p <  0.05), diabetic group (OR = 8.33, p = 0.003), and non-cardiovascular diseases (OR = 3.79, p <  0.001). CONCLUSIONS: Inadequate EI and MetS prevalence was high. Energy intake strongly determined MetS in different groups of hemodialysis patients.

A polygenic risk score for breast cancer risk in a Taiwanese population.

BACKGROUND: Multiple common variants identified by genome-wide association studies showed limited evidence of the risk of breast cancer in Taiwan. In this study, we analyzed the breast cancer risk in relation to 13 individual single-nucleotide polymorphisms (SNPs) identified by a GWAS in an Asian population. METHODS: In total, 446 breast cancer patients and 514 healthy controls were recruited for this case-control study. In addition, we developed a polygenic risk score (PRS) including those variants significantly associated with breast cancer risk, and also evaluated the contribution of PRS and clinical risk factors to breast cancer using receiver operating characteristic curve (AUC). RESULTS: Logistic regression results showed that nine individual SNPs were significantly associated with breast cancer risk after multiple testing. Among all SNPs, six variants, namely FGFR2 (rs2981582), HCN1 (rs981782), MAP3K1 (rs889312), TOX3 (rs3803662), ZNF365 (rs10822013), and RAD51B (rs3784099), were selected to create PRS model. A dose-response association was observed between breast cancer risk and the PRS. Women in the highest quartile of PRS had a significantly increased risk compared to women in the lowest quartile (odds ratio 2.26; 95% confidence interval 1.51-3.38). The AUC for a model which contained the PRS in addition to clinical risk factors was 66.52%, whereas that for a model which with established risk factors only was 63.38%. CONCLUSIONS: Our data identified a genetic risk predictor of breast cancer in Taiwanese population and suggest that risk models including PRS and clinical risk factors are useful in discriminating women at high risk of breast cancer from those at low risk.

MSH2 rs2303425 Polymorphism is Associated with Early-Onset Breast Cancer in Taiwan.

BACKGROUND: Accumulated evidence indicates that the incidence of early-onset breast cancer has rapidly increased in Taiwan and other Asian compared to Western countries. The mismatch repair (MMR) pathway might be one of the crucial mechanisms of predisposition to early breast cancer. In this study, we explored whether MMR gene polymorphisms contribute to the risk of breast cancer in young women. METHODS: This was a 2-stage case-control study including 737 cases and 719 controls. After eight single nucleotide polymorphisms (SNPs) were genotyped in MMR pathway genes in the stage I study, a promising SNP, MSH2 rs2303425, was selected for validation in the stage II study. A luciferase reporter assay was used to evaluate the transcriptional activity of MSH2. RESULTS: Logistic regression analysis showed that individuals with the MSH2 rs2303425 C/C genotype had a significantly increased risk of breast cancer compared to those with the T/T genotype (adjusted odds ratio 2.0; 95 % confidence interval 1.1-3.8), particularly in early-onset breast cancer patients with the luminal A subtype. The luciferase assay in three cell lines indicated that the MSH2 rs2303425 T/C substitution decreased MSH2 expression, which is consistent with the finding of an association study. CONCLUSIONS: A common variant SNP in MSH2 may contribute to the susceptibility to early-onset breast cancer functionally, particularly for the luminal A subtype.

The polymorphism XRCC1 Arg194Trp and 8-hydroxydeoxyguanosine increased susceptibility to arsenic-related renal cell carcinoma.

This study was designed to explore the relationship between X-ray repair cross-complementing group 1 (XRCC1) gene polymorphisms and renal cell carcinoma (RCC) and to investigate whether individuals with an XRCC1 risk genotype, a high level of 8-OHdG or a high urinary total arsenic concentration have a modified odds ratio (OR) of RCC. We recruited 180 RCC patients and 360 age- and sex-matched controls from a hospital-based pool. Image-guided biopsy or surgical resection of renal tumors was performed on RCC patients for pathological verification. Genomic DNA was used to examine the genotype of XRCC1(Arg399Gln), XRCC1(Arg194Trp), XRCC3(Thr241Met) and XPD(Lys751Gln) by PCR-RFLP. Liquid chromatography with tandem mass spectrometry was used to determine urinary 8-OHdG levels. A HPLC-HG-AAS was used to determine the concentrations of urinary arsenic species. Participants with the genotype XRCC1(Arg194Trp) Arg/Trp+Trp/Trp had a significantly higher OR of RCC than those with the Arg/Arg genotype; the OR and 95% confidence interval was 0.66 (0.45-0.97) after multivariate adjustment. The OR of RCC for the combined effect of high urinary 8-OHdG levels and high urinary total arsenic concentration in individuals with a XRCC1(Arg194Trp) Arg/Trp+Trp/Trp genotype was higher than in patients with an Arg/Arg genotype, which was evident in a dose response manner. In conclusion, this is the first study to show that the XRCC1 Arg194 allele is a predicting factor for RCC. The more risk factors (high urinary 8-OHdG levels, high urinary total arsenic concentrations, and XRCC1 Arg194 allele) that were present, the higher the OR of RCC.

Relation of polymorphism of arsenic metabolism genes to arsenic methylation capacity and developmental delay in preschool children in Taiwan.

Inefficient arsenic methylation capacity has been associated with developmental delay in children. The present study was designed to explore whether polymorphisms and haplotypes of arsenic methyltransferase (AS3MT), glutathione-S-transferase omegas (GSTOs), and purine nucleoside phosphorylase (PNP) affect arsenic methylation capacity and developmental delay. A case-control study was conducted from August 2010 to March 2014. All participants were recruited from the Shin Kong Wu Ho-Su Memorial Teaching Hospital. In total, 179 children with developmental delay and 88 children without delay were recruited. Urinary arsenic species, including arsenite (AsIII), arsenate (AsV), monomethylarsonic acid (MMAV), and dimethylarsinic acid (DMAV) were measured using a high-performance liquid chromatography-linked hydride generator and atomic absorption spectrometry. The polymorphisms of AS3MT, GSTO, and PNP were performed using the Sequenom MassARRAY platform with iPLEX Gold chemistry. Polymorphisms of AS3MT genes were found to affect susceptibility to developmental delay in children, but GSTO and PNP polymorphisms were not. Participants with AS3MT rs3740392 A/G+G/G genotype, compared with AS3MT rs3740392 A/A genotype, had a significantly lower secondary methylation index. This may result in an increased OR for developmental delay. Participants with the AS3MT high-risk haplotype had a significantly higher OR than those with AS3MT low-risk haplotypes [OR and 95% CI, 1.59 (1.08-2.34)]. This is the first study to show a joint dose-response effect of this AS3MT high-risk haplotype and inefficient arsenic methylation capacity on developmental delay. Our data provide evidence that AS3MT genes are related to developmental delay and may partially influence arsenic methylation capacity.

Kidney Cancer Linked to Chronic Hepatitis in the Asia-Pacific: A Population-Based Analysis.

BACKGROUND: The association of renal cancer with viral hepatitis infection remains unclear. Using an insurance data set, this population-based case-control study evaluated the association of renal cancer with chronic hepatitis virus infection in an endemic area of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. METHODS: We enrolled 17,747 patients with renal cancer during the period from 2000 to 2011 from the National Health Insurance Research Database of Taiwan. The control group comprised 35,494 randomly selected people without renal cancer matched by age and gender to the patients in the study group. ORs were calculated to assess the association of chronic hepatitis virus infection with renal cancer by using logistic regression analysis. RESULTS: Renal cancer was associated with HBV and HCV infection (OR 1.38, 95% CI 1.24-1.54; OR 1.24, 95% CI 1.07-1.44, respectively). An analysis stratified by gender and age revealed that young male HBV carriers had a higher risk of renal cancer compared with men without viral hepatitis (age <55 years: OR 1.94, 95% CI 1.57-2.39; 55≤ age <64 years: OR 1.40, 95% CI 1.05-1.86). Male HCV-infected patients aged <55 years (OR 1.90, 95% CI 1.11-3.26) and female HCV carriers aged between 55 and 64 years (OR 1.59, 95% CI 1.00-2.53) had a significantly higher risk of renal cancer compared with their counterparts. CONCLUSIONS: Renal cancer is significantly associated with chronic hepatitis infection, particularly in younger HBV-infected men.

Effect of Feedback Signal on Blood Pressure Self-regulation Capability in Individuals With Prehypertension or Stage I Hypertension: A Randomized Controlled Study.

OBJECTIVES: We aimed to determine the efficacy of an 8-week direct blood pressure (BP) biofeedback training program for prehypertensive or stage I hypertensive patients with a particular focus on the impact of the authenticity of feedback signals on the efficacy of BP regulation. DESIGNS: This study has a randomized, double-blind, parallel-group design. PARTICIPANTS AND METHODS: Fifty-nine individuals with ages from 18 to 64 years and who met the criteria for the diagnosis of prehypertenion or stage 1 hypertension participated in this study. The participants were referrals from physicians or community-dwelling volunteers. No participants had taken antihypertensive medication within the previous 2 months prior to enrollment. The participants were randomly assigned to the biofeedback group (n = 31) trained with real-time BP feedback signals or the control group (n = 28) trained with pseudofeedback signals. The primary outcome measures were systolic BP (SBP) and diastolic BP (DBP). Systolic BP and DBP were assessed at baseline, 1 week after training (week 9), and 8 weeks after training (week 16) in both groups. Only 54 participants had week 16 data. RESULTS: The changes in SBP and DBP from baseline to week 9, from baseline to week 16, and from week 9 to week 16 were not significantly different between the groups (All P > 0.05). Both groups were able to significantly decrease BP after completing the training. A percentage of 45.2% of the participants in the biofeedback group and 63.0% of the participants in the control group lowered their SBP by 5 mm Hg or more at week 9. The SBP-lowering effects were also maintained for at least 8 weeks after the completion of training. CONCLUSIONS: The equivalent magnitude of BP reduction between the 2 study groups suggests that repeated practice in BP self-regulation was more likely responsible for the efficacy of direct BP biofeedback training than was the type of feedback signals.

DNA methylation of PAX1 as a biomarker for oral squamous cell carcinoma.

OBJECTIVES: DNA methylation has been shown to be a promising cancer biomarker. The aim of this study was to evaluate DNA methylation of three transcription factors, sex-determining region Y-box 1 (SOX1), paired box gene 1 (PAX1), and zinc-finger 582 (ZNF582), in detecting oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: A case-control study was conducted at Taipei Medical University Hospital in Taiwan with 31 cases of various oral cavity squamous cell carcinomas and 40 controls. Questionnaire data assessing environmental exposure, such as alcohol consumption, cigarette smoking, and betel nut chewing, were obtained from each participant. DNA from oral swabs were analyzed for methylation using quantitative methylation polymerase chain reaction with TaqMan probes. Methylation status was determined using a methylation index. RESULTS: Methylation levels of SOX1, PAX1, and ZNF582 were significantly higher in cancer patients (p = 0.02, p = 0.02, and p = 0.03, respectively). Patients with highly methylated SOX1, PAX1, and ZNF582 had an increased cancer risk with odds ratios (ORs) of 16.50 (95 % CI = 2.85-96.65), 60.57 (95 % CI = 5.85-629.94), and 5.07 (95 % CI = 1.08-23.76), respectively. Area under the curve (AUC) values were 0.85, 0.78, and 0.78 for PAX1, SOX1, and ZNF582, respectively. When stratified based on environmental exposure, the AUC of PAX1 methylation (PAX1 (m) ) was 0.94 in environmental exposure-naïve subjects and 0.85 for SOX1 methylation in subjects who chewed betel nut. In general, the sensitivity and specificity of PAX1 (m) were 87 and 80 % for OSCC detection. The sensitivity of PAX1 (m) in subjects who chewed betel nut was 83 %, with a specificity of 75 %. CONCLUSIONS: Testing PAX1 DNA methylation using oral swabs is a promising method for oral cancer detection. Combined assessments regarding betel nut consumption and DNA methylation can improve OSCC screening. CLINICAL RELEVANCE: The double E (environmental and epigenetic) assessment is a potential strategy in OSCC screening.

The effect of cigarette smoke and arsenic exposure on urothelial carcinoma risk is modified by glutathione S-transferase M1 gene null genotype.

Inter-individual variation in the metabolism of xenobiotics, caused by factors such as cigarette smoking or inorganic arsenic exposure, is hypothesized to be a susceptibility factor for urothelial carcinoma (UC). Therefore, our study aimed to evaluate the role of gene-environment interaction in the carcinogenesis of UC. A hospital-based case-control study was conducted. Urinary arsenic profiles were measured using high-performance liquid chromatography-hydride generator-atomic absorption spectrometry. Genotyping was performed using a polymerase chain reaction-restriction fragment length polymorphism technique. Information about cigarette smoking exposure was acquired from a lifestyle questionnaire. Multivariate logistic regression was applied to estimate the UC risk associated with certain risk factors. We found that UC patients had higher urinary levels of total arsenic, higher percentages of inorganic arsenic (InAs%) and monomethylarsonic acid (MMA%) and lower percentages of dimethylarsinic acid (DMA%) compared to controls. Subjects carrying the GSTM1 null genotype had significantly increased UC risk. However, no association was observed between gene polymorphisms of CYP1A1, EPHX1, SULT1A1 and GSTT1 and UC risk after adjustment for age and sex. Significant gene-environment interactions among urinary arsenic profile, cigarette smoking, and GSTM1 wild/null polymorphism and UC risk were observed after adjustment for potential risk factors. Overall, gene-environment interactions simultaneously played an important role in UC carcinogenesis. In the future, large-scale studies should be conducted using tag-SNPs of xenobiotic-metabolism-related enzymes for gene determination.

Polymorphism of inflammatory genes and arsenic methylation capacity are associated with urothelial carcinoma.

Chronic exposure to arsenic can generate reactive oxidative species, which can induce certain proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and interleukin-8 (IL-8). TNF-α, IL-6 and IL-8 have been shown to be involved in the development and progression of various cancers, including bladder cancer. This study aimed to investigate the joint effect of the polymorphism of TNF-α -308 G/A, IL-6 -174 G/C, IL-8 -251 T/A and urinary arsenic profiles on urothelial carcinoma (UC) risk. This study evaluated 300 pathologically-confirmed cases of UC and 594 cancer-free controls. Urinary arsenic species were detected using high-performance liquid chromatography-linked hydride generator and atomic absorption spectrometry. The polymorphism of TNF-α -308 G/A, IL-6 -174 G/C and IL-8 -251 T/A was determined using polymerase chain reaction-restriction fragment length polymorphism. The joint effects on UC risk were estimated by odds ratios and 95% confidence intervals using unconditional logistic regression. We found that the TNF-α -308 A/A and IL-8 -251 T/T polymorphisms were significantly associated with UC. Moreover, significant dose-response joint effect of TNF-α -308 A/A or IL-8 -251 T/T genotypes and arsenic methylation indices were seen to affect UC risk. The present results also showed a significant increase in UC risk in subjects with the IL-8 -251 T/T genotype for each SD increase in urinary total arsenic and MMA%. In contrast, a significant decrease in UC risk was found in subjects who carried the IL-8 -251 T/T genotype for each SD increase in DMA%.

Genetic polymorphisms of myeloperoxidase and their effect on hypertension.

Myeloperoxidase (MPO) is a member of the mammalian peroxidase superfamily and plays specific roles in host defense. This study aimed to explore the association between one polymorphism of MPO and hypertension risk. Study subjects were recruited from Taipei City Hospital, Zhongxiao Branch, Taipei Medical University Hospital and Taipei Municipal WanFang Hospital. Participants completed questionnaires and provided blood samples. In this study we considered hypertension to be present among subjects that had blood pressures above 140/90 mmHg, or who had previously received treatment for hypertension. The polymorphism of MPO investigated in this study was constructed by performing a restriction fragment length polymorphism following polymerase chain reaction. This study found the odds ratio and 95% confidence interval for hypertension among subjects with the MPO -463 GA/AA genotype to be 1.97 (1.23-3.16) when compared with those with the GG genotype after multivariate adjustment. Participants with a body mass index (BMI) ≥ 24 kg/m(2) and with MPO -463 GA/AA genotype had a 4.60-fold increased risk of hypertension compared with those with a BMI < 24 kg/m(2) and with the GG genotype. This is the first study to conclude that the MPO -463 GA/AA genotype was associated with hypertension. In addition, we also detected that subjects with the MPO -463 GA/AA genotype that had higher BMIs and positive diabetes status tended to have higher risks of hypertension than subjects with the MPO -463 GA/AA genotype that had normal BMIs and were not diabetic.

The impact of occupational health service network and reporting system in Taiwan.

BACKGROUND: Underreporting occupational disease cases has been a long-standing problem in Taiwan, which hinders the progress in occupational health and safety. To address this problem, the government has founded the Network of Occupational Diseases and Injuries Service (NODIS) for occupational disease and injury services and established a new Internet-based reporting system. OBJECTIVES: The aims of this study are to analyze the possible influence of the NODIS, comprised of Center for Occupational Disease and Injury Services and their local network hospitals, on compensable occupational diseases and describe the distribution of occupational diseases across occupations and industries from 2005 to 2010 in Taiwan. METHODS: We conducted a secondary analysis of two datasets, including the NODIS reporting dataset and the National Labor Insurance scheme's dataset of compensated cases. For the NODIS dataset, demographics, disease distribution, and the time trends of occupational diseases were analyzed. The data of the Labor Insurance dataset was used to calculate the annual incidence of compensated cases. Furthermore, the annual incidence of reported occupational diseases from the NODIS was further compared with the annual incidence of compensable occupational diseases from the compensated dataset during the same period. RESULTS: After the establishment of the NODIS, the two annual incidence rates of reported and compensable occupational disease cases have increased by 1.2 and 2.0 folds from 2007 to 2010, respectively. The reason for this increased reporting may be the implementation of the new government-funded Internet-based system. The reason for the increased compensable cases may be the increasing availability of hospitals and clinics to provide occupational health services. During the 2008-2010 period, the most frequently reported occupational diseases were carpal tunnel syndrome, lumbar disc disorder, upper limb musculoskeletal disorders, and contact dermatitis. CONCLUSIONS: The new network and reporting system was successful in providing more occupational health services, providing more workers with compensation for occupational diseases, and reducing underreporting of occupational diseases. Therefore, the experience in Taiwan could serve as an example for other newly developed countries in a similar situation.

Risk perception, trust, and factors related to a planned new nuclear power plant in Taiwan after the 2011 Fukushima disaster.

After the Fukushima nuclear disaster in March 2011, an international review of nuclear safety indicated that two of the three nuclear power plants (NPPs) operating in Taiwan were listed as the most dangerous in the world. To understand the perception of NPP risks by the public in Taiwan and their attitudes regarding a planned fourth NPP after the Fukushima nuclear incident in 2011, a study was conducted in August 2011. A sample of 2819 individuals responded to the survey, with 66% perceiving that Taiwan's safety management of NPPs was inferior to Japan's, while 40% perceived a higher possibility of nuclear accidents like that in Japan. On average, a 'safe' distance of 94 km from an NPP was expected. 56% opposed the planned fourth NPP, with females (adjusted odd ratios (aOR) 2.03; 95% confidence interval (CI) 1.71-2.41), residence near the planned fourth NPP (aOR/CI 13.90/7.79-24.80), distrust of safety management (aOR/CI 1.98/1.45-2.69) and emergency planning (aOR/CI 1.89/1.49-2.40) as the main determinants. Others included those who expected larger safe distances from an NPP (trend test, p < 0.001), perceived excess cancer risks of living within 30 km of an NPP (aOR/CI 2.74/2.02-3.71), and projection of no electric shortage without NPPs (aOR/CI 1.93/1.50-2.49). Given that Taiwan's large population lives close to the existing NPPs and long-term concerns about the safety of these nuclear plants, the Fukushima incident in Japan likely augmented public risk perceptions on nuclear power in general and on the planned fourth NPP.