Article ID Journal Published Year Pages File Type
2148063 Mutation Research/Genetic Toxicology and Environmental Mutagenesis 2013 7 Pages PDF
Abstract

DNA damage induced by benzene and its metabolites is thought of as an important mechanism underlying benzene genotoxicity in chronic benzene poisoning (CBP). Therefore, genetic variation in DNA repair genes may contribute to susceptibility to CBP in the exposed population. Since benzene-induced DNA damages include DNA adducts, we hypothesized that the polymorphisms of ERCC1 (Excision repair cross complementation group 1) and ERCC2/XPD (Excision repair cross complementation group 2/xeroderma pigmentosum group D) are associated with the risk of CBP. A case-control study involving 102 benzene-poisoned patients and 204 none-benzene-poisoned controls occupationally exposed to benzene was carried out in the Northeast region of China. The polymorphisms of codon 118 (rs11615) and C8092A (rs3212986) of ERCC1, codon 751 (rs13181), 312 (rs1799793) and 156 (rs238406) of ERCC2/XPD were genotyped by TaqMan® Real-time PCR. The results showed that individuals carrying the ERCC1 codon 118 TT genotype had an increased risk of CBP (ORadj = 3.390; 95%CI: 1.393–8.253; P = 0.007) comparing with its CC genotype. After stratified by smoking, gender and exposure duration we found that the increased risk of CBP associated with the ERCC1 codon 118 TT genotype confined to nonsmokers (OR = 3.214; 95% CI: 1.359–7.601; P = 0.006), female (OR = 3.049; 95% CI: 1.235–7.529; P = 0.013) and exposure duration> 12 years (OR = 3.750; 95% CI: 1.041–13.513; P = 0.035). Since ERCC1 and ERCC2/XPD are both located on chromosome 19q13.3, haplotype analysis of all 5 SNPs was also conducted. However no correlations between the risks of CBP and other genotypes or haplotypes were found. Therefore, our findings suggest an important role of ERCC1 codon 118 polymorphisms for a biomarker to CBP in the Chinese occupational population.

► ERCC1 rs11615 TT genotype was associated with the high risk of CBP comparing with CC genotype. ► ERCC1 rs11615 SNP may be a valid biomarker to predict susceptibility of CBP in the study. ► A larger-scale study is needed to explore the effects of gene-environment interaction on CBP.

Related Topics
Life Sciences Biochemistry, Genetics and Molecular Biology Cancer Research
Authors
, , , , , , , ,