[Genetic susceptibility of DNA damage induced by vinyl chloride monomer exposure].
OBJECTIVE
To explore the association between DNA damage induced by vinyl chloride monomer (VCM) and polymorphisms of DNA repair genes and xenobiotic metabolism genes of VCM.


METHODS
Comet assay was employed to detect DNA damage. Based on the status of DNA damage, the VCM exposure workers were divided into two groups: DNA damage group (75) and control group (75). Case-control design was used to investigate the association between the genetic polymorphisms and DNA damage induced by VCM. Genotypes of XRCC1 (Arg194Trp, Arg280His and Arg399Gln), XPD (Ile199Met, Asp312Asn and Lys751Gln) and CYP2E1 were identified by the PCR-RFLP. PCR assay was used to detect positive and null genotype of GSTT1 and GSTM1.


RESULTS
Univariate analysis showed that the CYP2E1 c1c2/c2c2 and XPD751 Lys/Gln and Gln/Gln genotypes were significantly associated with the increased levels of DNA damage, XRCCI 339 Arg/Gln and Gln/Gln genotypes were significantly associated with the decreased levels of DNA damage (P < 0.01, P < 0.05, respectively). Logistic regression analysis showed that there was significant association between the genotypes of XRCC1 194, XRCC1 399, XPD 751, CYP2E1 and DNA damages. A prominent risk decreasing of DNA damage was observed for those individuals possessing XRCC1 399Arg/Gln + Gln/Gln genotypes (OR: 0.35, 95%CI: 0.12 approximately 1.01, respectively); The results also showed that there were significant associations between CYP2E1 c1c2/c2c2 and DNA damage both in high and low VCM-exposed groups (OR: 2.57, 95%CI: 1.01 approximately 6.59 and OR: 2.57, 95%CI: 0.99 approximately 6.87).


CONCLUSIONS
Cumulative exposure dose and genotypes of XRCC1 194, XRCC1 399, XPD 751 and CYP2E1 may modulate the DNA damage induced by VCM exposure.
Ji
Fang
F
Department of Occupational Health, School of Public Health, Fudan University, Key Laboratory of Public Health Safety, Ministry of Education, Shanghai 200032, China.
Zhu
Shou-Min
SM
Wang
Ai-Hong
AH
Qu
Ya-Bin
YB
Gu
Shou-Yong
SY
Zhu
Ren
R
Cai
Shang-Jian
SJ
Li
Jun
J
Xia
Zhao-Lin
ZL
D016022:Case-Control Studies; D020552:Comet Assay; D004249:DNA Damage / Q000187:drug effects*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D016273:Occupational Exposure; D020641:Polymorphism, Single Nucleotide; D014752:Vinyl Chloride / Q000633:toxicity*; D017132:Workplace
D014752:Vinyl Chloride