Susceptibility to eye diseases in relation to age and kidney failure among Taiwanese adults.

BACKGROUND: The kidney and eyes share common pathways and are thought to be closely connected. Chronic kidney disease and major eye diseases, such as cataract and glaucoma, are strongly associated with age. However, further investigation is needed to understand the joint impact of age and kidney diseases on eye diseases. In this study, we assessed the risk of eye diseases in relation to age and kidney failure in Taiwanese adults. METHODS: Our study included 127,561 cancer-free volunteers aged 30 to 70 years who participated in the Taiwan Biobank (TWB) project from 2008 to 2020. Information on the main exposures (kidney failure and age) and the outcome (eye diseases, including glaucoma, cataract, xerophthalmia, and retinal detachment) was collected through questionnaires. RESULTS: In general, kidney failure and older age were independently associated with a higher risk of eye, particularly cataract and retinal detachment: prevalence odds ratio (POR); 95% confidence interval (CI) = 2.480; 1.635-3.761 for cataract and 3.885; 1.968-7.666 for retinal detachment. A significant interaction between kidney failure and age on cataract was observed (p-value = 0.0002). Age-stratified analysis revealed a higher risk of cataract among patients with kidney failure aged below 50 (POR = 6.534; 95% CI = 2.493-17.124) and between 50 and 60 years (POR = 3.957; 95%CI = 1.986-7.881). Combining kidney failure and age (reference: no kidney failure and age < 50 years), kidney failure in all age groups was associated with a higher risk of cataract. The PORs; 95% CIs were 10.725; 4.227-27.211 for patients below 50 years, 28.487; 14.270-56.866 for those aged 50-60 years, and 43.183; 24.434-72.824 for those > 60 years. Combining cataract and age (reference: no cataract and age < 50 years), patients below 50 years had the highest risk of kidney failure (POR; 95% CI = 9.510; 3.722-24.297). CONCLUSIONS: Our study suggests that age and kidney failure may jointly contribute to eye diseases, particularly cataract. The association between cataract and kidney failure could be bidirectional, especially in individuals below 50 years. This significant bidirectional relationship underscores the need for screening patients with cataract for kidney failure and vice versa, particularly in younger adults.

Association between ESR1 rs2234693 single nucleotide polymorphism and uterine fibroids in Taiwanese premenopausal and postmenopausal women.

BACKGROUND: Uterine fibroids (UFs) are uterine smooth muscle neoplasms that affect women, especially during the reproductive stage. Both genetic and lifestyle factors affect the onset of the disease. We examined the association between the estrogen receptor 1 (ESR1) rs2234693 variant (whose genotypes are TT, TC, and CC) and UFs in Taiwanese premenopausal and postmenopausal women. METHODS: We linked individual-level data of 3588 participants from the Taiwan Biobank to the National Health Insurance Research Database at the Health and Welfare Data Science Center. The association of the ESR1 rs2234693 variant and other variables with UFs was determined by multiple logistic regression, and the results were presented as odds ratios and 95% confidence intervals (CIs). RESULTS: The 3588 participants comprised 622 cases and 2966 controls. In all the participants, the ESR1 rs2234693 TC and CC genotypes compared to the reference genotype (TT) were associated with a lower risk of UFs. However, the results were significant only for the CC genotype (OR; 95% CI = 0.70; 0.52-0.93). Noteworthy, the association of TC and CC with UFs was dose-dependent (p-trend = 0.012). Based on menopausal status, both TC and CC were significantly and dose-dependently associated with a lower risk of UFs in premenopausal women (OR; 95% CI = 0.76; 0.59-0.98 for TC and 0.64; 0.43-0.95 for CC: p-trend = 0.010). CONCLUSION: The TC and CC genotypes of the ESR1 rs2234693 variant may reduce susceptibility to UFs, especially in premenopausal women.

Cigarette smoking and PM2.5 might jointly exacerbate the risk of metabolic syndrome.

Background: Cigarette smoking and particulate matter (PM) with aerodynamic diameter < 2.5 µm (PM2.5) are major preventable cardiovascular mortality and morbidity promoters. Their joint role in metabolic syndrome (MS) pathogenesis is unknown. We determined the risk of MS based on PM2.5 and cigarette smoking in Taiwanese adults. Methods: The study included 126,366 Taiwanese between 30 and 70 years old with no personal history of cancer. The Taiwan Biobank (TWB) contained information on MS, cigarette smoking, and covariates, while the Environmental Protection Administration (EPA), Taiwan, contained the PM2.5 information. Individuals were categorized as current, former, and nonsmokers. PM2.5 levels were categorized into quartiles: PM2.5 ≤ Q1, Q1 < PM2.5 ≤ Q2, Q2 < PM2.5 ≤ Q3, and PM2.5 > Q3, corresponding to PM2.5 ≤ 27.137, 27.137 < PM2.5 ≤ 32.589, 32.589 < PM2.5 ≤ 38.205, and PM2.5 > 38.205 µg/m3. Results: The prevalence of MS was significantly different according to PM2.5 exposure (p-value = 0.0280) and cigarette smoking (p-value < 0.0001). Higher PM2.5 levels were significantly associated with a higher risk of MS: odds ratio (OR); 95% confidence interval (CI) = 1.058; 1.014-1.104, 1.185; 1.134-1.238, and 1.149; 1.101-1.200 for 27.137 < PM2.5 ≤ 32.589, 32.589 < PM2.5 ≤ 38.205, and PM2.5 > 38.205 µg/m3, respectively. The risk of MS was significantly higher among former and current smokers with OR; 95% CI = 1.062; 1.008-1.118 and 1.531; 1.450-1.616, respectively, and a dose-dependent p-value < 0.0001. The interaction between both exposures regarding MS was significant (p-value = 0.0157). Stratification by cigarette smoking revealed a significant risk of MS due to PM2.5 exposure among nonsmokers: OR (95% CI) = 1.074 (1.022-1.128), 1.226 (1.166-1.290), and 1.187 (1.129-1.247) for 27.137 < PM2.5 ≤ 32.589, 32.589 < PM2.5 ≤ 38.205, and PM2.5 > 38.205 µg/m3, respectively. According to PM2.5 quartiles, current smokers had a higher risk of MS, regardless of PM2.5 levels (OR); 95% CI = 1.605; 1.444-1.785, 1.561; 1.409-1.728, 1.359; 1.211-1.524, and 1.585; 1.418-1.772 for PM2.5 ≤ 27.137, 27.137 < PM2.5 ≤ 32.589, 32.589 < PM2.5 ≤ 38.205, and PM2.5 > 38.205 µg/m3, respectively. After combining both exposures, the group, current smokers; PM2.5 > 38.205 µg/m3 had the highest odds (1.801; 95% CI =1.625-1.995). Conclusion: PM2.5 and cigarette smoking were independently and jointly associated with a higher risk of MS. Stratified analyses revealed that cigarette smoking might have a much higher effect on MS than PM2.5. Nonetheless, exposure to both PM2.5 and cigarette smoking could compound the risk of MS.

ALDH7A1 rs12514417 polymorphism may increase ischemic stroke risk in alcohol-exposed individuals.

BACKGROUND: Epidemiological studies have identified common risk factors for cerebral stroke worldwide. Some of these factors include hypertension, diabetes, smoking, excessive drinking, and dyslipidemia. It is important to note, however, that genetic factors can also contribute to the occurrence of stroke. Here, we evaluated the association of ischemic stroke with rs12514417 polymorphism of the alcohol metabolizing gene, aldehyde dehydrogenase 7A1 (ALDH7A1) and alcohol consumption. METHODS: Taiwan Biobank (TWB) data collected between 2008 and 2015 were available for 17,985 subjects. The odd ratios for stroke were obtained using logistic regression models. RESULTS: Among eligible subjects (n = 17,829), 897 had ischemic stroke and 70 had hemorrhagic stroke. Subjects with ischemic stroke were older (mean ± SE, 58.45 ± 8.19 years vs. 48.33 ± 10.89 years, p < 0.0001) and had a higher body mass index (BMI) than the stroke-free individuals. The risk of ischemic stroke was significantly higher among subjects with the ALDH7A1 rs12514417 TG + GG genotype who also consumed alcohol at least 150 ml/week (odds ratio (OR), 1.79; 95% confidence interval (CI), 1.18-2.72). We found that rs12514417 genotype and alcohol consumption (at least 150 ml/week) showed a significant interaction (p for interaction = 0.0266). Stratification based on alcohol exposure and ALDH7A1 rs12514417 genotypes indicated that ischemic stroke risk was significantly higher among alcohol drinkers with the TG + GG genotype than in those with the TT genotype (OR, 1.64, 95% CI: 1.15-2.33). CONCLUSION: Our study suggests that the combination of ALDH7A1 rs12514417 TG + GG genotype and alcohol exposure of at least 150 ml/week may increase the risk of ischemic stroke in Taiwanese adults.

Risk of uterine leiomyoma based on BET1L rs2280543 single nucleotide polymorphism and vegetarian diet.

BACKGROUND: Bet1 Golgi vesicular membrane trafficking protein-like (BET1L) rs2280543 single nucleotide polymorphism (SNP) and diet have been independently associated with uterine leiomyoma (UL). However, whether the SNP and diet could jointly influence the risk of UL is yet to be assessed. Therefore, we investigated the independent and interactive effects of vegetarian diet and BET1L rs2280543 on uterine fibroids in Taiwanese women. METHODS: We linked participants' electronic data in the Taiwan Biobank (TWB) database to their medical records in the National Health Insurance Research Database (NHIRD). The TWB had genotypic, lifestyle, and biochemical data between 2008 and 2015 and the NHIRD had data on disease diagnoses between 1998 and 2015. In this study, we included 1997 premenopausal women with complete data. RESULTS: Compared  to participants with the BET1L rs2280543 CC genotype (wildtype), those with CT/CC genotype had an odds ratio (OR) of 0.69 and a 95% confidence interval (CI) of 0.51-0.93. Vegetarian diet and UL were not significantly associated: OR = 1.09 and 95% CI = 0.77-1.55. However, the test for interaction between rs2280543 and vegetarian diet was significant (p = 0.046). Compared to individuals with the CC genotype, the risk of UL was lower among vegetarians with the CT/TT genotype: OR (95% CI) = 0.15 (0.05-0.47). CONCLUSION: The BET1L rs2280543 CT/TT genotype was associated with a lower risk of UL especially among vegetarians.

Peripheral Vascular Disease Susceptibility Based on Diabetes Mellitus and rs17367504 Polymorphism of the MTHFR Gene.

PURPOSE: Peripheral vascular disease (PVD) is a life-threatening condition affecting the lower extremities. Common risk factors include type 2 diabetes (T2D), hypertension, dyslipidemia, smoking, and older age. There is a little-documented research on the genetic basis of the disease in Taiwan. We examined the impact of T2D and the blood pressure-associated rs17367504 variant of the Methylenetetrahydrofolate reductase (MTHFR) gene on PVD risk. MATERIALS AND METHODS: In this population-based association study, we linked data from 8992 participants in Taiwan Biobank (TWB) to their medical records in the National Health Insurance Research Database (NHIRD). Participants were 30 to 70 years old at recruitment and included those assessed between 2008 and 2015. We tested for association of PVD with rs17367504 and T2D using multiple logistic regression models. The rs17367504 variant was assessed using the Axiom-Taiwan Biobank Array Plate (TWB chip: Affymetrix, Inc., Santa Clara, CA, USA). RESULTS: Among cases with T2D (n = 1294), 158 (12.21%) were identified with PVD. T2D was associated with PVD (odds ratio [OR], 1.52; 95% confidence interval [CI], 1.21-1.91; p<0.001) whereas rs17367504 variant was not (OR, 0.96; CI, 0.76-1.21; p = 0.728 in AG/GG compared to AA homozygotes). However, T2D and rs17367504 had an interactive effect on PVD (p for interaction = 0.0076). Results from our stratified analyses displayed OR of 1.75 (CI, 1.35-2.26; p<0.001) in AA individuals with DM and 0.94 (CI, 0.56-1.58; p = 0.811) in AG+GG individuals with T2D. Using the AA genotype and no T2D as the reference group, the respective OR of PVD was 1.77 (CI, 1.38-2.28; p<0.001) in AA individuals with T2D; 1.18 (CI, 0.91-1.55; p = 0.215) in AG+GG individuals with no T2D, and 1.03 (CI, 0.66-1.60; p = 0.892) in AG+GG individuals with T2D . CONCLUSION: We found that type 2 diabetes was associated with increased risk of peripheral vascular disease, particularly in AA genotype carriers of the rs17367504 variant in Taiwan.

Association of ADH1B polymorphism and alcohol consumption with increased risk of intracerebral hemorrhagic stroke.

BACKGROUND: Alcohol consumption is one of the modifiable risk factors for intracerebral hemorrhage, which accounts for approximately 10-20% of all strokes worldwide. We evaluated the association of stroke with genetic polymorphisms in the alcohol metabolizing genes, alcohol dehydrogenase 1B (ADH1B, rs1229984) and aldehyde dehydrogenase 2 (ALDH2, rs671) genes based on alcohol consumption. METHODS: Data were available for 19,500 Taiwan Biobank (TWB) participants. We used logistic regression models to test for associations between genetic variants and stroke. Overall, there were 890 individuals with ischemic stroke, 70 with hemorrhagic stroke, and 16,837 control individuals. Participants with ischemic but not hemorrhagic stroke were older than their control individuals (mean ± SE, 58.47 ± 8.17 vs. 48.33 ± 10.90 years, p < 0.0001). ALDH2 rs671 was not associated with either hemorrhagic or ischemic stroke among alcohol drinkers. However, the risk of developing hemorrhagic stroke was significantly higher among ADH1B rs1229984 TC + CC individuals who drank alcohol (odds ratio (OR), 4.85; 95% confidence interval (CI) 1.92-12.21). We found that the test for interaction was significant for alcohol exposure and rs1229984 genotypes (p for interaction = 0.016). Stratification by alcohol exposure and ADH1B rs1229984 genotypes showed that the risk of developing hemorrhagic stroke remained significantly higher among alcohol drinkers with TC + CC genotype relative to those with the TT genotype (OR, 4.43, 95% CI 1.19-16.52). CONCLUSIONS: Our study suggests that the ADH1B rs1229984 TC + CC genotype and alcohol exposure of at least 150 ml/week may increase the risk of developing hemorrhagic stroke among Taiwanese adults.

Risk of gout among Taiwanese adults with ALDH-2 rs671 polymorphism according to BMI and alcohol intake.

BACKGROUND: Gout stems from both modifiable and genetic sources. We evaluated the risk of gout among Taiwanese adults with aldehyde dehydrogenase-2 (ALDH2) rs671 single nucleotide polymorphism (SNP) according to body mass index (BMI) and alcohol drinking. METHODS: We obtained information of 9253 individuals having no personal history of cancer from the Taiwan Biobank (2008-2016) and estimated the association between gout and independent variables (e.g., rs671, BMI, and alcohol drinking) using multiple logistic regression. RESULTS: Alcohol drinking and abnormal BMI were associated with a higher risk of gout whereas the rs671 GA+AA genotype was associated with a lower risk. The odds ratios (ORs) and 95% confidence intervals (CIs) were 1.297 and 1.098-1.532 for alcohol drinking, 1.550 and 1.368-1.755 for abnormal BMI, and 0.887 and 0.800-0.984 for GA+AA. The interaction between BMI and alcohol on gout was significant for GG (p-value = 0.0102) and GA+AA (p-value = 0.0175). When we stratified genotypes by BMI, alcohol drinking was significantly associated with gout only among individuals with a normal BMI (OR; 95% CI = 1.533; 1.036-2.269 for GG and 2.109; 1.202-3.699 for GA+AA). Concerning the combination of BMI and alcohol drinking among participants stratified by genotypes (reference, GG genotype, normal BMI, and no alcohol drinking), the risk of gout was significantly higher in the following categories: GG, normal BMI, and alcohol drinking (OR, 95% CI = 1.929, 1.385-2.688); GG, abnormal BMI, and no alcohol drinking (OR, 95% CI, = 1.721, 1.442-2.052); GG, abnormal BMI, and alcohol drinking (OR, 95% CI = 1.941, 1.501-2.511); GA+AA, normal BMI, and alcohol drinking (OR, 95% CI = 1.971, 1.167-3.327); GA+AA, abnormal BMI, and no alcohol drinking (OR, 95% CI = 1.498, 1.256-1.586); and GA+AA, abnormal BMI, and alcohol drinking (OR, 95% CI = 1.545, 1.088-2.194). CONCLUSIONS: Alcohol and abnormal BMI were associated with a higher risk of gout, whereas the rs671 GA+AA genotype was associated with a lower risk. Noteworthy, BMI and alcohol had a significant interaction on gout risk. Stratified analyses revealed that alcohol drinking especially among normal-weight individuals might elevate the risk of gout irrespective of the genotype.

Interactive association between dietary fat and sex on CDH13 cg02263260 methylation.

BACKGROUND: DNA methylation of Cadherin 13 (CDH13), a tumor suppressor gene is associated with gene repression and carcinogenesis. We determined the relation of dietary fat and sex with CDH13 cg02263260 methylation in Taiwanese adults. METHODS: Data of 870 eligible participants (430 men and 440 women) between 30 and 70 years were obtained from the Taiwan Biobank (TWB) database. The association of dietary fat and sex with CDH13 cg02263260 methylation was determined using multiple linear regression. RESULTS: The association between sex and cg02263260 methylation was significant: beta-coefficient (ß) = 0.00532; 95% confidence interval (CI) = 0.00195-0.00868. Moreover, the interaction between sex and dietary fat on cg02263260 methylation was significant (P-value = 0.0145). After stratification by sex, the association of dietary fat with cg02263260 methylation was significant only in women. Specifically, high dietary fat was positively associated with cg02263260 methylation in women (ß = 0.00597; 95% CI = 0.00061-0.01133) and the test for trend was significant (P-value = 0.0283). CONCLUSION: High fat intake was significantly associated with higher cg02263260 methylation in women and the test for trend was significant. These findings suggest that the association of fat intake and CDH13 cg02263260 might vary by sex and CDH13 cg02263260 methylation levels in women might increase as fat intake increases.

Interactive associations of sex and hyperlipidemia with calcific tendinitis of the shoulder in Taiwanese adults.

Calcific tendinitis (CT) of the shoulder is a painful disorder usually identified in individuals aged 40 and 60 years. The estimated global prevalence of CT is 2.7% to 36%. We examined the association of hyperlipidemia and sex with CT of the shoulder using Taiwan Biobank (TWB) and the National Health Insurance Research Database (NHIRD).Data were available for 9903 TWB participants who were recruited between 2008 and 2015. We used multiple logistic regression analysis to estimate the odds ratios (OR) and 95% confidence intervals (CI) for CT of the shoulder.Overall, 1564 women, and 1491 men were identified with hyperlipidemia. Women, compared to men, had higher odds of CT of the shoulder (OR, 1.53; 95% CI, 1.08-2.16). Hyperlipidemia, compared to no hyperlipidemia, was associated with an increased risk of CT (OR, 1.40; 95% CI, 1.02-1.93). The test for interaction was significant for sex and hyperlipidemia (P = .006). After stratification, the odds ratio for CT was 1.95 (95% CI, 1.30-2.92) in women and 0.82 (95% CI, 0.48-1.39) in men, respectively. Compared to men with no hyperlipidemia, the odds ratio was 0.86 (95% CI, 0.53-1.38) for men with hyperlipidemia and 2.00 (95% CI, 1.29-3.10) for women with hyperlipidemia.Importantly, our findings indicated that the risk for CT of the shoulder was higher among Taiwanese women with hyperlipidemia. However, CT risk among their male counterparts with hyperlipidemia was not significant.

PM2.5 exposure and DLEC1 promoter methylation in Taiwan Biobank participants.

BACKGROUND: Particulate matter (PM) < 2.5 µm (PM2.5) or fine PM is a serious public health concern. It affects DNA methylation and heightens carcinogenesis. Deleted in lung and esophageal cancer 1 (DLEC1) is a tumor suppressor gene. However, aberrant methylation of the gene is associated with several cancers. We evaluated the association between PM2.5 and DLEC1 promoter methylation in Taiwanese adults based on regular outdoor exercise. METHODS: We obtained DNA methylation and exercise data of 496 participants (aged between 30 and 70 years) from the Taiwan Biobank (TWB) database. We also extracted PM2.5 data from the Air Quality Monitoring Database (AQMD) and estimated participants' exposure using residential addresses. RESULTS: DLEC1 methylation and PM2.5 were positively associated: beta coefficient (ß) = 0.114 × 10-3; p value = 0.046. The test for interaction between exercise and PM2.5 on DLEC1 methylation was significant (p value = 0.036). After stratification by exercise habits, PM2.5 and DLEC1 methylation remained significantly associated only among those who exercised regularly (ß = 0.237 × 10-3; p value = 0.007). PM2.5 quartile-stratified analyses revealed an inverse association between regular exercise and DLEC1 methylation at PM2.5 < 27.37 µg/m3 (ß = - 5.280 × 10-3; p value = 0.009). After combining exercise habits and PM2.5 quartiles, one stratum (i.e., regular exercise and PM2.5 < 27.37 µg/m3) was inversely associated with DLEC1 methylation (ß = -5.160 × 10-3, p value = 0.007). CONCLUSIONS: We found significant positive associations between PM2.5 and DLEC1 promoter methylation. Regular exercise at PM2.5 < 27.37 µg/m3 seemingly regulated DLEC1 promoter methylation.

AHRR cg05575921 methylation in relation to smoking and PM2.5 exposure among Taiwanese men and women.

BACKGROUND: Polycyclic aromatic hydrocarbon (PAH)-rich substances like cigarette smoke and PM2.5 induce aryl hydrocarbon receptor (AHR)-mediated aryl hydrocarbon receptor repressor (AHRR) methylation. AHRR cg05575921 and coagulation factor II (thrombin) receptor-like 3 (F2RL3) cg03636183 methylation patterns are well-established biomarkers for smoking. Even though AHRR cg05575921 methylation has recently been associated with PM2.5, the interaction between smoking and PM2.5 on AHRR methylation is yet to be fully explored. We evaluated AHRR and F2RL3 CpG sites to identify potential significant markers in relation to PM2.5 and smoking in Taiwanese adults. METHODS: DNA methylation and smoking data of 948 participants aged 30-70 years were obtained from the Taiwan Biobank Database (2008-2015), while PM2.5 data were obtained from the Air Quality Monitoring Database (2006-2011). RESULTS: Smoking and PM2.5 were independently associated with hypomethylation (lower levels) of AHRR cg05575921, AHRR cg23576855, F2RL3 cg03636183, and F2LR3 cg21911711 after multiple-comparison correction (Bonferroni P < 0.00028409). Cg05575921 was the most hypomethylated AHRR CpG site, while cg03636183 was the most hypomethylated F2RL3 CpG site. Overall, cg05575921 was the most hypomethylated CpG site: ß = - 0.03909, P < 0.0001; - 0.17536, P < 0.0001 for former and current smoking, respectively (P-trendsmoking < 0.0001) and - 0.00141, P < 0.0001 for PM2.5. After adjusting for F2RL3 cg03636183, smoking and PM2.5 remained significantly associated with cg05575921 hypomethylation: ß - 0.02221, P < 0.0001; - 0.11578, P < 0.0001 for former and current smoking, respectively (P-trendsmoking < 0.0001) and - 0.0070, P = 0.0120 for PM2.5. After stratification by sex, smoking and PM2.5 remained associated (P < 0.05) with cg05575921 hypomethylation in both men (ß = - 0.04274, - 0.17700, and - 0.00163 for former smoking, current smoking, and PM2.5, respectively) and women (ß = - 0.01937, - 0.17255, and - 0.00105 for former smoking, current smoking, and PM2.5, respectively). After stratification by residential area, former and current smoking remained associated (P < 0.05) with cg05575921 hypomethylation: ß = - 0.03918 and - 0.17536, respectively (P-trendsmoking < 0.0001). Living in the central and southern areas was also associated (P < 0.05) with cg05575921 hypomethylation: ß = - 0.01356 and - 0.01970, respectively (P-trendarea < 0.0001). CONCLUSION: Smoking and PM2.5 were independently associated with hypomethylation of cg05575921, cg23576855, cg03636183, and cg21911711. The most hypomethylated CpG site was cg05575921 and its association with smoking and PM2.5 was dose-dependent.

Blood-Based SOX2-Promoter Methylation in Relation to Exercise and PM2.5 Exposure among Taiwanese Adults.

Increased ventilation during exercise in polluted areas could trigger airway inflammation. We evaluated blood DNA methylation of the SOX2-promoter region in relation to exercise and PM2.5 in Taiwanese adults. Data of 948 participants aged 30-70 years were retrieved from the Taiwan Biobank Database (2008-2015) and the Air Quality Monitoring Database (2006-2011). PM2.5 was positively associated with SOX2-promoter methylation (ß = 0.000216; p < 0.0001). The interaction between PM2.5 and exercise on SOX2-promoter methylation was significant (p = 0.0146). After stratification by exercise habits, PM2.5 was positively associated with SOX2 methylation in only individuals who did regular exercise (ß = 0.0003490; p < 0.0001). After stratification by exercise habits and residential areas, SOX2-promoter methylation levels in those who lived in the southern area were higher for both the regular exercise (ß = 0.00272; p = 0.0172) and no regular exercise groups (ß = 0.002610 and p = 0.0162). SOX2-promoter methylation levels in those who lived in the northern area and did regular exercise were lower; ß = -0.00314 (p = 0.0036). In conclusion, PM2.5 was positively associated with SOX2-promoter methylation in participants who did regular exercise. Living in the southern area was positively associated with SOX2-promoter methylation regardless of exercise habits.

Association between coarse particulate matter (PM10-2.5) and nasopharyngeal carcinoma among Taiwanese men.

The nasopharyngeal tract traps mainly coarse particles in inhaled air. Soluble carcinogenic compounds, endotoxins, and trace metals contained in these particles are potential causes of inflammation and oxidative stress which could enhance carcinogenesis. The aim of this study was to determine the association between coarse particulate matter (PM10-2.5) and nasopharyngeal cancer (NPC). A total of 521,098 men (355 cases and 520,743 non-cases), aged ≥40 years were included in this study. Data were retrieved from the Taiwan Cancer Registry, the Adult Preventive Medical Services Database, and the Air Quality Monitoring Database. PM10-2.5 was significantly associated with a higher risk of NPC after adjusting for SO2, NOx, O3, age, body mass index, smoking, alcohol drinking, betel nut chewing, exercise, hypertension, diabetes, and hyperlipidemia. With PM10-2.5<20.44 µg/m3 as the reference, the ORs and 95% CIs were 1.47; 1.03-2.11, 1.34; 0.94-1.91, and 1.68; 1.16-2.44 for 20.44≤PM10-2.5<24.08, 24.08≤PM10-2.5<29.27, and PM10-2.5≥29.27 µg/m3, respectively. PM10-2.5 remained significantly associated with a higher risk of NPC after further adjustments were made for the aforementioned covariates and PM2.5 The ORs; 95% CIs were 1.42; 0.96 to 2.12, 1.41; 0.94 to 2.10, and 1.71; 1.10 to 2.66 for 20.44≤PM10-2.5<24.08, 24.08≤PM10-2.5<29.27, and PM10-2.5≥29.27 µg/m3, respectively. In conclusion, PM10-2.5 was significantly associated with a higher risk of NPC in Taiwanese men.

Online community collaborative map: A geospatial and data visualization tool for cancer data.

The aim of this study was to develop an online collaborative map to enable researchers to locate, explore, and share cancer data.This 2-scale (global and country-level) cancer map adopts a database-driven model, which was implemented using the Google Map Application Programming Interface (API) and asynchronous JavaScript and XML (AJAX) technology. Seven visualization techniques were used to present data. Data on worldwide cancer mortality between 1950 and 2013 were taken from the International Agency for Research on Cancer (IARC) database. Incidence data were from the IARC CI5plus database. Survival data were from the IARC SURVCAN study. Prevalence data between 1990 and 2017 were from the Institute for Health Metrics and Evaluation's (IHME) catalog while demographic data were from the World Bank Data Catalog. Cancer data for Taiwan between 1991 and 2016 were obtained from the Department of Health and Welfare. This study used visualization techniques that included: a choropleth map to display the prevalence of cancer; a tornado diagram to show the age-standardized mortality rates of all cancers among men and women in 2013; a treemap to show a ranking of cancer mortality data; a sunburst chart to show mortality rates of all cancers by gender; a line chart to show mortality trends for all cancers; a bar chart to show mortality and incidence rates and a heatmap to show variations in cancer across different countries.The world cancer map generated by this study can be accessed at http://worldmap.csmu-liawyp.tw. Country-level mortality data are presented as crude and age-standardized rates.We used visualization methodologies and constructed an easily maintainable web-based user interface with cancer data from administrative regions in 150 countries. This serves as a platform that allows researchers to manage and disseminate cancer data.

Methylation at cg05575921 of a smoking-related gene (AHRR) in non-smoking Taiwanese adults residing in areas with different PM2.5 concentrations.

BACKGROUND: DNA methylation is associated with cancer, metabolic, neurological, and autoimmune disorders. Hypomethylation of aryl hydrocarbon receptor repressor (AHRR) especially at cg05575921 is associated with smoking and lung cancer. Studies on the association between AHRR methylation at cg05575921 and sources of polycyclic aromatic hydrocarbon (PAH) other than smoking are limited. The aim of our study was to assess the pattern of blood DNA methylation at cg05575921 in non-smoking Taiwanese adults living in areas with different PM2.5 levels. METHODS: Data on blood DNA methylation, smoking, and residence were retrieved from the Taiwan Biobank dataset (2008-2015). Current and former smokers, as well as individuals with incomplete information were excluded from the current study. The final analysis included 708 participants (279 men and 429 women) aged 30-70 years. PM2.5 levels have been shown to increase as one moves from the northern through central towards southern Taiwan. Based on this trend, the study areas were categorized into northern, north-central, central, and southern regions. RESULTS: Living in PM2.5 areas was associated with lower methylation levels: compared with the northern area (reference area), living in north-central, central, and southern areas was associated with lower methylation levels at cg05575921. However, only methylation levels in those living in central and southern areas were significant (ß = - 0.01003, P = 0.009 and ß = - 0.01480, P < 0.001, respectively. Even though methylation levels in those living in the north-central area were not statistically significant, the test for linear trend was significant (P < 0.001). When PM2.5 was included in the regression model, a unit increase in PM2.5 was associated with 0.00115 (P < 0.001) lower cg05575921 methylation levels. CONCLUSION: Living in PM2.5 areas was inversely associated with blood AHRR methylation levels at cg05575921. The methylation levels were lowest in participants residing in southern followed by central and north-central areas. Moreover, when PM2.5 was included in the regression model, it was inversely associated with methylation levels at cg05575921. Blood methylation at cg05575921 (AHRR) in non-smokers might indicate different exposures to PM2.5 and lung cancer which is a PM2.5-related disease.

SOX2 promoter hypermethylation in non-smoking Taiwanese adults residing in air pollution areas.

BACKGROUND: Both SOX2 promoter methylation and air pollution have been associated with lung cancer risk. However, little has been done to assess SOX2 promoter methylation in individuals living in air pollution areas. The aim of this study was to investigate SOX2 promoter methylation in non-smoking Taiwanese adults living in areas with different levels of air pollution especially particulate matter with diameter < 2.5 µm (PM2.5). METHODS: A total of 1142 individuals aged 30-70 years were recruited. Data on SOX2 methylation, residence, age, and exposure to second-hand smoke (SHS) among others were extracted from the Taiwan Biobank dataset (2008-2015). After excluding former and current smokers, alongside those with incomplete information, a total of 461 non-smokers comprising 176 men and 285 women were included in the study. Participants' residences were grouped under northern and central/southern areas because air pollution (PM2.5) is lower in northern compared to central and southern areas. RESULTS: The methylation levels in men (0.16310 ± 0.01230) and women (0.15740 ± 0.01240) were significantly different (P < .0001). In both sexes, the SOX2 promoter region was shown to be significantly hypermethylated in central and southern areas compared with the northern areas. The regression coefficient (ß) was 0.00331 (P = 0.0257) in men and 0.00514 (P < .0001) in women. CONCLUSION: SOX2 was significantly hypermethylated in both men and women residing in central and southern areas. The consistency in the results for both sexes shows that SOX2 promoter methylation could serve as a potential biomarker for industrial air pollution exposure. Moreover, it might reflect predisposition to cancer. Hence, healthy non-smokers at precancerous stages who have not been clinically diagnosed could be identified.

Association between fine particulate matter and oral cancer among Taiwanese men.

The aim of this study was to investigate the association between fine particulate matter 2.5 (PM2.5) and oral cancer among Taiwanese men. Four linked data sources including the Taiwan Cancer Registry, Adult Preventive Medical Services Database, National Health Insurance Research Database, and Air Quality Monitoring Database were used. Concentrations of sulfur dioxide, carbon monoxide, ozone, NOx (nitrogen monoxide and nitrogen dioxide), coarse particulate matter (PM10-2.5) and PM2.5 in 2009 were assessed in quartiles. A total of 482 659 men aged 40 years and above were included in the analysis. Logistic regression was used to examine the association between PM2.5 and oral cancer diagnosed from 2012 to 2013. After adjusting for potential confounders, the ORs of oral cancer were 0.91 (95% CI 0.75 to 1.11) for 26.74≤PM2.5<32.37, 1.01 (95% CI 0.84 to 1.20) for 32.37≤PM2.5<40.37 µg/m3 and 1.43 (95% CI 1.17 to 1.74) for PM2.5≥40.37 µg/m3 compared with PM2.5<26.74 µg/m3 In this study, there was an increased risk of oral cancer among Taiwanese men who were exposed to higher concentrations of PM2.5.

HDL and associated factors stratified by sex and menopausal status: results from a community-based survey in Taiwan.

AIM: To investigate factors, especially modifiable factors associated with high-density lipoprotein (HDL) in Taiwanese based on sex and menopausal status. MATERIALS AND METHODS: Participants comprised 2022 men and 2392 women (1267 menopausal and 1125 non-menopausal) aged ≥30 years who resided in Pingzhen district, Taoyuan from 2006-2011. Their data, obtained through questionnaires and measurements were retrieved from the Li-Shin Hospital. RESULTS: Higher HDL was associated with total cholesterol, underweight, and alcohol drinking in both men and women. It was also associated with education, blood group B, and marital status in men as well as with age in women. Moreover, it was associated with total cholesterol, underweight, and age in both menopausal and non-menopausal women. Furthermore, it was associated with marital status in non-menopausal women and alcohol drinking in menopausal women. Lower HDL was associated with triglycerides, low-density lipoprotein (LDL), overweight, obesity, waist-hip ratio (WHR), uric acid, and smoking in both men and women and with coffee drinking in only women. It was also associated with uric acid, triglycerides, LDL, overweight, obesity, WHR, and body fat in both menopausal and non-menopausal women. Moreover, it was associated with coffee drinking in menopausal women. CONCLUSION: Modifiable factors associated with HDL differ according to sex and menopausal status. Sex and menopausal status should be considered when implementing lifestyle changes to raise HDL. For example, both men and women should maintain a normal weight as well as quit smoking.

Duration-response association between exercise and HDL in both male and female Taiwanese adults aged 40 years and above.

BACKGROUND: Exercise is an important cardiovascular risk reducing therapy. OBJECTIVE: The aim of this study was to assess the relationship between weekly exercise duration and high-density lipoprotein cholesterol (HDL-c) in Taiwanese men and women. METHODS: Data were retrieved from the dataset of the national adult preventive medical services which is recorded under the Health Promotion Administration (HPA). The lipid profiles of 194528 eligible participants aged 40 years and above who completed a questionnaire on recent health behavior including smoking, drinking, exercise and other factors in 2014 were determined. Weekly exercise durations of 0.0, <2.5 and ≥2.5 hours were classified as no, below recommended and recommended, respectively. The relationship between exercise and HDL-c was determined using linear regression. RESULTS: After multivariate adjustments, a duration-response association existed between exercise and HDL-c (P-trend <0.0001) in both sexes. Weekly exercise durations of <2.5 and ≥2.5 hours were both positively associated with HDL-c (P <0.0001) in both sexes. However, the associations were stronger in males than females in both exercise groups. Smoking (P <0.05) and BMI (P <0.0001) were negatively associated while drinking was positively associated with HDL-c in both sexes. CONCLUSION: This study demonstrated a duration-response association between exercise and HDL-c. Exercise at durations below the minimum weekly recommendation of 2.5 hours was positively associated with HDL-c.