DNA repair gene polymorphisms and micronucleus frequencies in Chinese workers exposed to vinyl chloride monomer

Abstract

Vinyl chloride monomer (VCM) is genotoxic and cancerogen agent. Individual variations in response to the exposure have been noticed and the variations may be due to genetic differences in the removal of VCM-DNA adducts, such as polymorphism in genes NER pathway and BER pathway. This study explores the relationship between genetic polymorphism of seven genes within the NER pathway (XPA, XPD, XPC, XPG, XPF, and ERCC1) and BER pathway (APE1), and susceptibility to chromosomal damage after exposure to VCM. One hundred and eighty workers occupationally exposed to VCM and 43 unexposed controls were investigated. Chromosome damage in peripheral lymphocytes was measured by the cytokinesis-blocked micronucleus assay. PCR-RFLP technique was applied to detect polymorphisms of the seven genes. The influence of genotype, age, gender, cumulative exposure dose, alcohol consumption, and smoking status on the frequencies of MN was determined using univariate and multiple Poisson regression analyses. We found XPA A23G variant workers had significantly higher MN frequencies than those from the wild-type homozygous counterparts (P = 0.01). Those with the variant XPD Lys751Gln genotype had marginally higher MN frequencies (P = 0.07). On the other hand, XPC PAT and XPF 5'-UTR T2063A variant workers had significantly lower MN frequencies compared with those from their wild-type homozygous counterparts (P = 0.04 and P = 0.004, respectively). Our findings suggest that XPC PAT, XPD Lys751Gln, XPA A23G and XPF 5'-UTR T2063A contribute to the level of chromosome damage in occupational exposure to VCM in Chinese population.