Chung-Li Du

Effects on sister chromatid exchange frequency of aldehyde dehydrogenase 2 genotype and smoking in vinyl chloride workers

Vinyl chloride monomer (VCM) is a human carcinogen. However, the exact mechanism of carcinogenesis remains unclear. VCM may be metabolized by cytochrome P450 2E1 (CYP2E1), aldehyde dehydrogenase 2 (ALDH2) and glutathione S-transferases (GSTs). Thus workers with inherited variant metabolic enzyme activities may have an altered risk of genotoxicity. This study was designed to investigate which risk factors might affect sister chromatid exchange (SCE) frequency in polyvinyl chloride (PVC) workers. Study subjects were 44 male workers from three PVC factories. Questionnaires were administered to obtain detailed histories of cigarette smoking, alcohol consumption, occupations, and medications. SCE frequency in peripheral lymphocytes was determined using a standardized method, and CYP2E1, GSTM1, GSTT1 and ALDH2 genotypes were identified by the polymerase chain reaction (PCR). Analysis revealed that smoking status and exposure to VCM were significantly associated with increased SCE frequency. The presence of ALDH2 1-2/2-2 genotypes was also significantly associated with an elevation of SCE frequency (9. 5 vs. 8.1, p<0.01). However, CYP2E1, GSTM1 or GSTT1 genotypes were not significantly associated with SCE frequency. When various genotypes were considered together, combination of CYP2E1 c1c2/c2c2 with ALDH2 1-2/2-2 showed an additive effect on SCE frequency. Similar results were also found for the combination of smoking with CYP2E1, or smoking with ALDH2. These results suggest that VCM workers with ALDH2 1-2/2-2 genotypes, who also smoke, may have increased risk of DNA damage.

Increased morbidity odds ratio of primary liver cancer and cirrhosis of the liver among vinyl chloride monomer workers.

OBJECTIVES: To determine if there is an increased risk of admission to hospital for various diseases among vinyl chloride monomer (VCM) workers. METHODS: 2224 workers with occupational exposure to VCM were identified for occurrence of disease based on a search of hospital computer files on labour insurance. These data were compared with those of workers manufacturing optical equipment and motorcycles from 1 January 1985 to 31 March 1994. Cardiovascular and cerebrovascular diseases were used as reference diseases, and the age adjusted morbidity odds ratio (MOR) was calculated. RESULTS: A significantly increased risk of admission to hospital among VCM workers due to primary liver cancer (MOR 4.5-6.5), cirrhosis of the liver (MOR 1.7-2.1), and other chronic diseases (MOR 1.5-2.0) was found. There were eight cases of primary liver cancer, all with heavy previous exposure to VCM. Another four cases of hepatoma in polyvinyl chloride (PVC) workers were found in the death registry. Ten out of 11 cases of hepatoma, with detailed medical information, were carriers of hepatitis B virus. The average latent period (20 years) was not different from other studies. Alternative agents of primary liver cancer were largely ruled out, suggesting that the combination of hepatitis B and VCM may lead to primary liver cancer. CONCLUSION: There is an increased risk of primary liver cancer in workers exposed to VCM, although the incomplete coverage of the Labor Insurance Bureau data warrants cautious interpretation of the results. Further study exploring the synergistic effects of VCM and hepatitis B is also indicated.

An increased standardised mortality ratio for liver cancer among polyvinyl chloride workers in Taiwan

Aims: To determine the standardised mortality ratio (SMR) corresponding to different causes of death in workers from polyvinyl chloride polymerisation factories in Taiwan. Methods: Retrospective cohort study of workers from six polyvinyl chloride polymerisation factories in Taiwan. A total of 3293 male workers who had been employed for at least one year during the period 1 January 1950 to 31 December 1992, and were alive on 1 January 1985 were included for analysis. Using data acquired from Taiwans National Mortality Registry, it was found that 144 of these workers died during the period 1985–97. The follow up rate was 99% with a total number of person-years at risk of 40 557. Results: SMR for all causes of death was 0.78, indicating a possible “healthy worker” effect. The SMR for liver cancer decreased with increasing age of first exposure to vinyl chloride monomer. This association was more prominent for workers who were first employed in the industry prior to 1970 (SMR 4.82). Medical records indicated that most liver cancers in this study were hepatocellular carcinoma. Conclusions: Polyvinyl chloride workers may experience a higher risk of developing liver cancer, particularly hepatocelluar carcinoma.

Working hours, sleep duration and the risk of acute coronary heart disease: A case–control study of middle-aged men in Taiwan

BACKGROUND This study aimed to examine whether long working hours and short sleep duration were associated with an increased risk of acute myocardial infarction (AMI) or severe coronary heart diseases (SCHD), independent of established psychosocial work-related factors. METHODS A case-control study was conducted. Cases were 322 men, aged <60 years and economically active, who were admitted to hospital with a first diagnosed AMI or SCHD during 2008-2011, of whom 134 were confirmed AMI and the other 188 were angiography-confirmed SCHD. Controls were 644 men who were drawn from a national survey and were matched to the cases on age, education and area of residence. Odds ratios of total CHD and confirmed AMI in relation to average weekly working hours and daily hours of sleep were calculated. RESULTS Men with average working hours longer than 60 h/week were found to have significantly increased risks for total CHD (OR=2.2) as compared to those with weekly working hours in 40-48 h, and those with daily hours of sleep fewer than 6 h were found to have increased risks for CHD (OR=3.0) as compared to those with sleeping hours in 6-9 h. Restriction to confirmed AMI yielded a greater risk and these associations remained consistent with adjustment of smoking status, body mass index and psychosocial work factors including job demands, job control, workplace justice, job insecurity and shift work. CONCLUSION The results support the hypothesis that long working hours and short sleep duration contribute independently to the risk of cardiovascular diseases in men.

Plasma p53 protein and anti-p53 antibody expression in vinyl chloride monomer workers in Taiwan.

Vinyl chloride (VC) workers are known to be at risk for development of angiosarcoma of the liver (ASL), a rare tumor. Previously, a study of p53 gene mutations in tumors of VC-exposed workers found that 50% of liver angiosarcomas contained such mutations. Mutant p53 oncoprotein and anti-p53 antibodies can also be found in the sera of ASL patients and VC-exposed workers without cancer. Workers in Taiwan have also been exposed to VC, and some have contracted liver tumors. In this study, we used enzyme-linked immunosorbent assays to detect mutant p53 protein and anti-p53 antibodies in the plasma of VC-exposed workers in Taiwan. Thirty-three of 251 (13.2%) VC-workers tested positive for the p53 overexpression (10% with positive mutant p53 protein and 3.6% with positive anti-p53) in their plasma, but only 2 of 36 controls (5.6%) tested positive (2.8% with positive mutant p53 protein and 2.8% with positive anti-p53). There was a significant association between cumulative VC exposure concentration and positive p53 expression (P = 0.032) among VC workers after we adjusted for age, hepatitis, drinking, and smoking status. In summary, P53 overexpression (mutant p53 protein or anti-p53 antibody) can be found in the plasma of VC workers in Taiwan, and a significant dose-response relationship exists between plasma p53 overexpression and VC cumulative exposure concentration.

Increased morbidity from nasopharyngeal carcinoma and chronic pharyngitis or sinusitis among workers at a newspaper printing company

Objectives: To determine the association between printing works and nasopharygeal carcinoma as well as other diseases. Methods: Demographic data were obtained for those who had worked in a particular newspaper company since its establishment in 1950. Through access to the data bank of the hospital records of the Labor Insurance Bureau for 1985–94, all workers were identified who had been admitted to hospital during their employment in the newspaper company. Multiple logistic regressions were performed to estimate the adjusted morbidity odds ratio (OR) for various diseases among the printing workers with cardiovascular diseases as the reference diseases. Biopsy specimens from patients with nasopharyngeal carcinoma were all subjected to in situ hybridisation of Epstein-Barr virus (EBV), and colocalisation of EBV and secretor component protein. Results: Of the 1564 people who had worked in this company, 579 of them were admitted to hospital at least once. Five out of 144 printing workers admitted to hospital were diagnosed with nasopharyngeal carcinoma compared with none of the other 435 non-printing workers admitted to hospital. The morbidity OR for nasopharyngeal carcinoma in printing workers was 57.0 (95% confidence interval (95% CI) 2.8 to 1155.3). The morbidity OR for benign skin tumours was 28.0 (95% CI 2.7 to 293.1). Chronic pharyngitis or sinusitis also showed significant relations with printing works with a morbidity OR 29.4 (95% CI 1.7 to 514.7). Using all other diseases as the reference diseases for calculation of morbidity ORs still showed a similar trend. In situ hybridisation of EBV encoded small nuclear RNA-1 (EBER-1) showed tumour cells free of the EBV in each biopsy specimen. Colocalisation of EBER-1 and secretor component showed that some tumour cells contained both secretor component and EBV signal in each case. Conclusion: Printing works are associated with an increased risk of nasopharyngeal carcinoma, benign skin tumours, chronic pharyngitis or sinusitis, chronic liver diseases, and mechanical injuries. Induction of the development of nasopharyngeal carcinoma is probably not related to EBV infection in these patients.

Delayed Return-to-work in Workers After Non-severe Occupational Upper Extremity Fracture in Taiwan

BACKGROUND/PURPOSE Occupational injury of the upper extremities account for 24% of occupational injuries in Taiwan. However, studies on the timing and factors influencing return-to-work are lacking. METHODS A total of 102 hospitalized workers with non-severe upper extremity fractures, defined as without avulsion, amputation and nerve damage, were interviewed over the telephone using a structured questionnaire at 45, 90 and 180 days after injury. RESULTS After controlling other factors, cases with other-than-digit fracture presented three-fold more difficulty than those with digit fracture on returning to work (OR, 0.32; 95% CI, 0.17-0.63). Male workers (OR, 2.70; 95% CI, 1.16-6.25) and those with financial help from their employer (OR, 2.32; 95% CI, 1.17-4.60) found it easier to return to work 90 days after injury. There were 32% who were still unable to return to work 180 days after injury. CONCLUSION Women workers and workers without financial help from employers are at a disadvantage with regard to early return-to-work. Other assistance besides medical treatment could be of significant help but should be cautiously exercised in extrapolating to workers who are not the main breadwinner in their household.

Interaction of vinyl chloride monomer exposure and hepatitis B viral infection on liver cancer

Learning ObjectivesIdentify previously reported findings relating occupational vinyl chloride monomer (VCM) exposure to liver disease.Relate how - and to what extent - hepatitis B surface antigen (HBsAg) status and particular job-related tasks interact to increase the risk of hepatocellular carcinoma in workers exposed to VCM.Explain postulated mechanisms by which hepatitis B virus infection and VCM exposure may interact to cause liver cancer. Vinyl-chloride monomer (VCM), a human carcinogen, has caused angiosarcoma of the liver. Recent studies have shown that VCM exposure is associated with hepatocellular cancer. In Taiwanese studies, the majority of VCM-exposed workers with liver cancer had history of hepatitis B virus (HBV) infection. To determine the role of HBV on the development of liver cancer in the VCM-exposed workers, we conducted a case-control study from a previously established polyvinyl chloride (PVC) cohort consisting of 4096 male workers from six PVC polymerization plants. A total of 18 patients with liver cancer, and 68 control subjects matched for age and specific plant of employment were selected. Detailed history of the participants that included alcohol consumption status, cigarette use, occupation, and family history of chronic liver disease were obtained using an interviewer-administered questionnaire. When the HBV surface antigen (HBsAg)-negative subjects without history of tank-cleaning were used as the reference, the HBsAg-negative subjects with history of tank-cleaning demonstrated a 4.0-fold greater risk of liver cancer (95% confidence interval: 95% CI = 0.2–69.1). The HBsAg carriers without history of tank-cleaning revealed a 25.7-fold greater risk of liver cancer (95% CI = 2.9–229.4). Whereas the HBsAg carriers with history of tank-cleaning revealed the greatest risk (matched odds ratio (ORm) 396.0, 95% CI = 22.6–∞) of developing liver cancer among subjects with different VCM-exposure status and HBsAg status categories. Further analysis showed the interaction term was significant (P < .01). Therefore, our results suggest an interaction between occupational VCM exposure and HBV infection for the development of liver cancer.

Changes in lymphocyte single strand breakage and liver function of workers exposed to vinyl chloride monomer

Vinyl chloride monomer (VCM) is a suspected human carcinogen. Its metabolite, chloroethylene epoxide, is able to alkylate the DNA molecule and to produce single strand breakage (SSB). A total of 244 workers from 4 polyvinyl chloride (PVC) manufacturing factories were recruited to assess the SSB of their peripheral lymphocyte DNA. The method of alkaline unwinding and hydroxyapatite chromatography was used to detect and calculate frequencies of SSB. In addition, hepatitis B and C markers and the liver function of the workers were also examined. The workers cumulative exposures to VCM were retrospectively constructed from the current monitoring data and each workers job history. Multiple linear regression models were constructed to predict the workers level of SSB and liver functions based on various exposure indices and variables, such as age, sex, smoking, drinking, and hepatitis markers. The results showed that current smoking and drinking status, and the presence of VCM exposures on the previous day were 3 major determinants of the level of SSB. Among the liver function tests, only gamma-glutamyl transpeptidase (GGT) was associated with current VCM exposures. In contrast, aspartate aminotransferase (AST), alkaline phosphatase (ALP) and alanine aminotransferase (ALT) were mainly affected by the presence of hepatitis B surface antigen (HBsAg) or anti-hepatitis C virus (anti-HCV). We conclude that GGT should be considered to be included in the regular health screening of VCM workers, and that the SSB method may not be suitable for long-term monitoring of cumulative exposure because of the quick DNA repair mechanism in humans.

Correlation of Occupational Stress Index with 24-hour Urine Cortisol and Serum DHEA Sulfate among City Bus Drivers: A Cross-sectional Study

Objectives The questionnaire of occupational stress index (OSI) has been popular in the workplace, and it has been tailored for bus drivers in Taiwan. Nevertheless, its outcomes for participants are based on self-evaluations, thus validation by their physiological stress biomarker is warranted and this is the main goal of this study. Methods A cross-sectional study of sixty-three city bus drivers and fifty-four supporting staffs for comparison was conducted. Questionnaire surveys, 24-hour urine cortisol testing, and blood draws for dehydroepiandrosterone-sulfate (DHEA-S) testing were performed. The measured concentrations of these biological measures were logarithmically transformed before the statistical analysis where various scores of stressor factors, moderators, and stress effects of each OSI domain were analyzed by applying multiple linear regression models. Results For drivers, the elevated 24-hour urine cortisol level was associated with a workers relationship with their supervisor and any life change events in the most recent 3 months. The DHEA-S level was higher in drivers of younger age as well as drivers with more concerns relating to their salary and bonuses. Non-drivers showed no association between any stressor or satisfaction and urine cortisol and blood DHEA-S levels. Conclusion Measurements of biomarkers may offer additional stress evaluations with OSI questionnaires for bus drivers. Increased DHEA-S and cortisol levels may result from stressors like income security. Prevention efforts towards occupational stress and life events and health promotional efforts for aged driver were important anti-stress remedies.