title: Polymorphisms and haplotypes of DNA repair and xenobiotic metabolism genes and risk of DNA damage in Chinese vinyl chloride monomer (VCM)-exposed workers.
abstract: In this case-control study, we investigated the association between DNA damage and genetic susceptibility among vinyl chloride monomer (VCM)-exposed workers. The cumulative exposure dose of VCM was calculated based on the workers' duration of exposure and the geometric mean concentration of VCM in the workplace. DNA damage to peripheral blood lymphocytes was measured by single cell gel electrophoresis (SCGE) assay, and single nucleotide-polymorphisms (SNPs) in xenobiotic metabolism and DNA repair genes were detected by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods. Univariate analysis showed that the CYP2E1 c1c2/c2c2 and XPD751 Lys/Gln and Gln/Gln genotypes were significantly associated with the levels of DNA damage (P<0.01 and 0.05, respectively). Further logistic regression analysis showed a significant association between CYP2E1 c1c2/c2c2 and DNA damage, and risk of having increased levels of DNA damage was more pronounced in those individuals having XRCC1 194 mutant genotypes and/or XPD751 Lys/Gln and Gln/Gln genotypes. Although most of the XPD and XRCC1 haplotypes did not show any significant difference, the XRCC1 haplotype Trp194-Arg280 was significantly over-represented in the case group (P<0.05; OR 2.09; 95% CI: 1.07-4.06) than in controls. Overall, our data suggest that the genotypes of CYP2E1, XRCC1 194, and XPD 751 were associated with the level of DNA damage and may contribute to individual sensitivity to DNA damage induced by VCM in the workplace.
authors.affiliation: Department of Occupational Health and Toxicology, School of Public Health, Fudan University, Shanghai, China.
authors.forename: Shou-Min
authors.initials: SM
authors.lastname: Zhu
authors.forename: Zhao-Lin
authors.initials: ZL
authors.lastname: Xia
authors.forename: Ai-Hong
authors.initials: AH
authors.lastname: Wang
authors.forename: Xue-Feng
authors.initials: XF
authors.lastname: Ren
authors.forename: Jie
authors.initials: J
authors.lastname: Jiao
authors.forename: Nai-Qing
authors.initials: NQ
authors.lastname: Zhao
authors.forename: Ji
authors.initials: J
authors.lastname: Qian
authors.forename: Li
authors.initials: L
authors.lastname: Jin
authors.forename: David C
authors.initials: DC
authors.lastname: Christiani
mesh_terms: D000328:Adult; D000465:Algorithms; D000704:Analysis of Variance; D002681:China; D004249:DNA Damage / Q000502:physiology*; D004260:DNA Repair / Q000187:drug effects*; D004798:Enzymes / Q000235:genetics; D005260:Female; D005819:Genetic Markers; D005838:Genotype; D006239:Haplotypes / Q000187:drug effects; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016273:Occupational Exposure / Q000009:adverse effects*; D011110:Polymorphism, Genetic / Q000187:drug effects*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012907:Smoking / Q000453:epidemiology; D014752:Vinyl Chloride / Q000633:toxicity*; D015262:Xenobiotics / Q000378:metabolism*
chemical_list: D004798:Enzymes; D005819:Genetic Markers; D015262:Xenobiotics; D014752:Vinyl Chloride