Study on Liver Damage in Workers Exposed to Vinyl Chloride Monomer

• Main Authors: Hui-I Hsieh, 謝蕙宜
• Other Authors: Tsun-Jen Cheng
• Format: Others
• Language: en_US
• Published: 2010
• Online Access: http://ndltd.ncl.edu.tw/handle/33592965968527980123

博士 === 臺灣大學 === 職業醫學與工業衛生研究所 === 98 === Exposure to vinyl chloride monomer (VCM) may induce a rare cancer, liver angiosarcoma (LAS), and thus VCM is classified as a group 1 human carcinogen by the International Agency for Research on Cancer. Previous studies found occupational VCM exposure increased the risk of developing acute and chronic liver diseases. VCM exposure may also increase the risk of developing cancers other than LAS, especially hepatocellular carcinoma (HCC). However, because the evidence on the association between VCM exposure and diseases or cancers other than LAS is less consistent and the pathogenesis is less clear, more studies should be conducted. First, factors affecting carcinogenesis include age, genetic susceptibility, exposure dose, and general health conditions. Second, chronic hepatitis and liver cirrhosis are the major risk factors associated with HCC; therefore, studies on known factors and certain diseases should contribute to our understanding of the mechanisms involved in VCM-related liver damage, especially those that lead to HCC. The polyvinyl chloride (PVC) industry had a history of more than 50 years in Taiwan. More than 4,000 workers have participated in the related processes and some workers have been exposed to high levels of VCM. The aim of the thesis is to study the association between VCM exposure and certain cancers, and investigate the modifying effects of other known risk factors on the VCM-induced liver damage through a continuing follow-up of a Taiwanese occupational cohort. The findings could provide evidence of how VCM induces HCC. In the first part of this thesis, a retrospective study was conducted to estimate the cause-specific mortality, from 1980 and 2007, among 3,336 workers from six PVC factories in Taiwan. The standardized mortality ratio (SMR) was calculated and the moving average of the SMR was used to observe the mortality trends for cancers of a priori interest. 360 deaths were found with an excess risk of liver cancer mortality as compared to the general Taiwanese male population. Time trend analysis revealed that there is an inverted U-shape curve of mortality from liver cancer, hemolymphopoietic cancer and leukemia. Clinical evidence supported the suggestion that most liver cancer deaths should be HCC cases. The results of our study add more evidence to the association between VCM exposure and HCC, hemolymphopoietic cancer and leukemia. Adequate control of VCM exposure at worksites may thus contribute to the decline of the cancer mortality. In the second part of the thesis, a cross-sectional study was conducted to study the synergistic effect of occupational chemical exposure and hepatitis viral infection on serum aminotransferase activity. 568 male workers who were employed in five PVC or four VCM factories were enrolled. Among workers without hepatitis viral infection, the differences in prevalence of abnormal AST and ALT were not significant between the different chemical exposure groups. In workers with hepatitis viral infection, those with high exposure had a higher prevalence of abnormal AST and ALT compared to those with low exposure. Mixed exposures to 1,2-ethylene dichloride and VCM appear to have a positive synergistic effect with hepatitis viral infection on liver damage. In the third part of the thesis, a cross-sectional study was conducted to evaluate if metabolizing genetic polymorphisms could modify individual susceptibility to liver fibrosis with VCM exposure. CYP2E1, ALDH2, and GSTT1 polymorphisms were determined by the PCR-RFLP method among 320 workers who were employed in five PVC plants. Cumulative VCM exposure levels for study subjects were calculated using a job exposure matrix model. Thirteen workers were diagnosed as having liver fibrosis by ultrasound. We observed a dose–response trend between VCM exposure and liver fibrosis. Regarding the results on genetic polymorphisms, the CYP2E1 c2c2 genotype showed a significant effect on liver fibrosis as compared to those with other genotypes. No differences were observed between GSTT1 and ALDH2 genotypes. Our results suggest that the CYP2E1 genotype may be responsible for individual differences in susceptibility to liver fibrosis with regard to chronic VCM exposure. Thus, polymorphism analysis of metabolizing enzymes might be useful in the risk assessment of liver damage in VCM-exposed workers. We continued to observe the PVC cohort and found that workers had a high risk of mortality from liver cancer, leukemia and hemolymphopoietic cancer. High exposure doses of VCM with hepatitis viral infection and the CYP2E1 c2c2 genotype increased the risk of liver damage. Our study provides evidence on the association between VCM exposure and the development of hepatitis, liver fibrosis and HCC. Our study also contributes to an understanding of the mechanisms involved in VCM-related liver damage and can be used as a guide for the prevention of such damage.