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Microsomal epoxide hydrolase (EPHX1) polymorphisms are associated with aberrant promoter methylation of ERCC3 and hematotoxicity in benzene-exposed workers
Xing, Caihong1,2,3; Chen, Qi4; Li, Guilan3; Zhang, Linyuan3; Zheng, Min3; Zou, Zhengyong2; Hou, Lifang5,6; Wang, Qian-Fei2; Liu, Xin4,5; Guo, Xinbiao1
关键词occupational exposure microsomal epoxide hydrolase genetic polymorphism ERCC3 methylation
刊名ENVIRONMENTAL AND MOLECULAR MUTAGENESIS
2013-07-01
DOI10.1002/em.21786
54期:6页:397-405
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Environmental Sciences ; Genetics & Heredity ; Toxicology
资助者National Natural Science Foundation of China ; National Institute for Occupational Health and Poison Control, China CDC ; National Natural Science Foundation of China ; National Institute for Occupational Health and Poison Control, China CDC
研究领域[WOS]Environmental Sciences & Ecology ; Genetics & Heredity ; Toxicology
关键词[WOS]CHINESE OCCUPATIONAL POPULATION ; DNA-REPAIR GENES ; LUNG-CANCER ; EXPRESSION ; DAMAGE ; RISK ; SUSCEPTIBILITY ; METABOLITES ; COHORT ; HUMANS
英文摘要

Benzene is an important industrial chemical and widespread environmental pollutant known to induce leukemia and other blood disorders. To be carcinogenic, benzene must be metabolized to produce toxic metabolites. To investigate whether single nucleotide polymorphisms (SNPs) in the metabolic enzyme genes are associated with benzene-induced alterations in DNA methylation and hematotoxicity, we genotyped four commonly studied SNPs in three metabolic enzymes genes CYP1A1, EPHX1 and NQO1; and analyzed promoter DNA methylation status in 11 genes which have been reported to be associated with benzene-induced hematotoxicity (BLM, CYP1A1, EPHX1, ERCC3, NQO1, NUDT1, p15, p16, RAD51, TP53 and WRAP53) in 77 benzene-exposed workers and 25 unexposed controls in China. ERCC3, a DNA repair gene, showed a small but statistically significant increase of promoter DNA methylation in the exposed group compared with the unexposed group (mean +/- SD: 4.73 +/- 3.46% vs. 3.63 +/- 1.96%, P=0.048). We also observed that an increased number of C allele for rs1051740 in EPHX1 was associated with decreased ERCC3 methylation levels in benzene-exposed workers (P-trend=0.001), but not in unexposed controls (P-trend=0.379). Interestingly, another EPHX1 SNP (rs2234922) was associated with lower white blood cell (WBC) counts (P-trend=0.044) in benzene-exposed workers. These associations remained the same when ERCC3 promoter methylation and WBCs were dichotomized according to the 90th percentile (6%) of methylation levels in controls and a leucopenia cutoff (<4 x 10(9)/L), respectively. Our findings suggest that benzene exposure may be associated with hypermethylation in ERCC3, and that genetic variants in EPHX1 may play an important role in epigenetic changes and hematotoxicity among benzene-exposed workers. Environ. Mol. Mutagen. 54:397-405, 2013. (c) 2013 Wiley Periodicals, Inc.

语种英语
所属项目编号81270612
资助者National Natural Science Foundation of China ; National Institute for Occupational Health and Poison Control, China CDC ; National Natural Science Foundation of China ; National Institute for Occupational Health and Poison Control, China CDC
WOS记录号WOS:000321295400003
引用统计
被引频次:17[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/64274
专题北京大学公共卫生学院
作者单位1.Peking Univ, Sch Publ Hlth, Dept Occupat & Environm Hlth Sci, Beijing 100191, Peoples R China
2.Chinese Acad Sci, Beijing Inst Genom, Lab Dis Genom & Individualized Med, Beijing, Peoples R China
3.Chinese Ctr Dis Control & Prevent, Natl Inst Occupat Hlth & Poison Control, Key Lab Chem Safety & Hlth, Beijing, Peoples R China
4.Northwestern Univ, Dept Pediat,Feinberg Sch Med, Mary Ann & J Milburn Smith Child Hlth Res Program, Ann & Robert H Lurie Childrens Hosp Chicago Res C, Chicago, IL 60611 USA
5.Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA
6.Northwestern Univ, Feinberg Sch Med, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA
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GB/T 7714
Xing, Caihong,Chen, Qi,Li, Guilan,et al. Microsomal epoxide hydrolase (EPHX1) polymorphisms are associated with aberrant promoter methylation of ERCC3 and hematotoxicity in benzene-exposed workers[J]. ENVIRONMENTAL AND MOLECULAR MUTAGENESIS,2013,54(6):397-405.
APA Xing, Caihong.,Chen, Qi.,Li, Guilan.,Zhang, Linyuan.,Zheng, Min.,...&Guo, Xinbiao.(2013).Microsomal epoxide hydrolase (EPHX1) polymorphisms are associated with aberrant promoter methylation of ERCC3 and hematotoxicity in benzene-exposed workers.ENVIRONMENTAL AND MOLECULAR MUTAGENESIS,54(6),397-405.
MLA Xing, Caihong,et al."Microsomal epoxide hydrolase (EPHX1) polymorphisms are associated with aberrant promoter methylation of ERCC3 and hematotoxicity in benzene-exposed workers".ENVIRONMENTAL AND MOLECULAR MUTAGENESIS 54.6(2013):397-405.
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