Historical cohort study of 10 109 men in the North American vinyl chloride industry, 1942–72: update of cancer mortality to 31 December 1995

Abstract

Objectives-To update and assess mortality from neoplasms to 31 December 1995 among 10 109 men employed in a job exposed to vinyl chloride for at least 1 year between 1942 and 1972 at any of 37 North American factories. Previous analyses indicated associations between employment in vinyl production and increased mortality risk from cancers of the liver and biliary tract, due to increased mortality from angiosarcoma of the liver, and brain cancer. Methods-Standardised mortality ratio (SMR) analyses, overall and stratified by several work related variables, were conducted with United States and state reference rates. Cox's proportional hazards models and stratified log rank tests were used to further assess occupational factors. Results-895 of 3191 deaths (28%) were from malignant neoplasms, 505 since the previous update to the end of 1982. Mortality from all causes showed a deficit (SMR 83, 95% confidence interval (95% CI) 80 to 86), whereas mortality from all cancers combined was similar to state referent rates. Mortality from cancers of the liver and biliary tract was clearly increased (SMR 359, 95% CI 284 to 446). Modest excesses of brain cancer (SMR 142, 95% CI 100 to 197) and cancer of connective and soft tissue (SMR 270, 95% CI 139 to 472) were found. Stratified SMR and Cox's proportional hazard analyses supported associations with age at first exposure, duration of exposure, and year of first exposure for cancers of the liver and soft tissues, but not the brain. Conclusions-Excess mortality risk from cancer of the liver and biliary tract, largely due to angiosarcoma, continues. Risk of mortality from brain cancer has attenuated, but its relation with exposure to vinyl chloride remains unclear. A potentially work related excess of deaths from cancer of connective and soft tissue was found for the first time, but was based on few cancers of assorted histology. (Occup Environ Med 2000;57:774-781)

Meta-analysis of studies of occupational exposure to vinyl chloride in relation to cancer mortality

“…Out of 16 cases of liver cancer in the study from Taiwan (13) with known HBV status, 15 were positive for the virus. Furthermore, in the three studies providing relevant results (4,5,13), the mortality from liver cancer (excluding angiosarcoma of the liver) was almost completely offset by a corresponding decrease in mortality from liver cirrhosis, a finding suggesting that vinyl chloride enhances carcinogenesis in an otherwise chronically damaged liver.…”

“…Two large, multicenter epidemiologic studies of workers exposed to vinyl chloride have been reported recently (4)(5). Their results are also available as detailed reports (6)(7).…”

“…The increase in the meta-SMR was mainly due to the North American multicenter study, in which the excess of mortality was most apparent between 1970 and 1979, but not in subsequent years (4). In neither of the two large studies was a trend with duration of exposure suggested (figure 3).…”

“…Two of the studies selected for the meta-analysis (4,5) were multicenter investigations including, or overlapping with, populations studied by other authors. The European multicenter study (5,14) included most of the persons previously studied in the United Kingdom (15,16), Norway (17,18), Italy (19,20), and Sweden (21-23), but the populations described in national reports did not completely overlap with those in the large multicenter study, due to different entry criteria (table 2).…”

Correlation of chromosome damage and promoter methylation status of the DNA repair genes MGMT and hMLH1 in Chinese vinyl chloride monomer (VCM)-exposed workers

“…Vinyl chloride monomer (CH2 = CHCl, VCM), a chemical widely used in the manufacture of polyvinyl chloride (PVC) plastics, causes angiosarcoma and hepatocellular cancer (HCC) [1][2][3] and is a known human and rodent carcinogen [4]. In the liver, VCM is primarily metabolized by the cytochrome P450 system to chloroethylene oxide (CEO) [5], which can either undergo hydrolysis or rearrange rapidly to the more stable chloroacetaldehyde (CAA).…”