Published online Oct 7, 2005. doi: 10.3748/wjg.v11.i37.5821
Revised: December 23, 2004
Accepted: December 26, 2004
Published online: October 7, 2005
AIM: The permissible exposure limit (PEL) of vinyl chloride monomer (VCM) in developed country was 1 p/m (2.79 mg/m3); and threshold limit value-short term exposure limit (TLV-STEL) in China was 11 times higher [11 p/m (30 mg/m3)] than it, till 2002. The mechanism of vinyl chloride monomer (VCM)-related carcinogenesis remains unclear. We aimed to analyze occupational health hazards exposure to doses lower than the Chinese occupational health standard in a selected VC polymerization plant in China, and also to elucidate the relationship between genetic polymorphisms and genetic susceptibility on liver lesions of workers exposed to VCM.
METHODS: In order to explore the mechanism of VCM-related health effects, we used a case-control design to investigate the association between the genetic polymorphisms of metabolic enzymes and liver lesions in workers occupationally exposed to VCM. Genotypes of CYP2E1, GSTT1, GSTM1, ALDH2 and ADH2 were identified using PCR and PCR-RFLP.
RESULTS: Even when the concentration of VCM was lower than the current Chinese occupational health standard, neurasthenia, pharyngeal irritation, liver ultrasonography abnormalities and hemoglobin disorders were significantly higher in exposure subjects compared to non-exposure subjects, and the relative risks (RR and 95% CI) were 1.74 (1.06-2.85), 1.97 (1.56-2.48), 10.69 (4.38-26.12), and 2.07 (1.20-3.57). CYP2E1 c1c2/c2c2 genotype was significantly associated with liver damages (OR 3.29, 95% CI 1.51-7.20, P < 0.01).
CONCLUSION: The incidences of neurasthenia and liver ultrasonography abnormalities significantly increase when the cumulative exposure dose increases. The genotypes of metabolic enzymes (CYP2E1 c1c2/c2c2, null GSTT1 and ADH2 1-1) play important roles in VCM metabolism. Polymorphisms of CYP 2E1, GSTT1 and ADH2 may be a major reason of genetic susceptibility in VCM-induced hepatic damage.