Effect of polymorphic metabolizing genes on micronucleus frequencies among benzene-exposed shoe workers in China.
It is well-known that metabolism of benzene is required for the induction of toxicity and consequent health problems. Therefore, genetic variation in benzene (BZ) metabolism genes can influence health outcomes. However, large population studies are needed to provide more evidence for such relationship. We have conducted a large population investigation (385 BZ-exposed shoe workers and 197 matched healthy controls) on the association between inheritance of certain BZ metabolizing genes and the expression of micronuclei (MN). The latter was based on the cytokinesis-blocked MN assay. We analyzed the polymorphisms of GSTM1, GSTT1, GSTP1 (rs1695), CYP2E1 (rs3813867), CYP2E1 (rs2031920), CYP2E1 (rs6413432), mEH exon 3 (rs1051740), mEH exon 4 (rs2234922). Univariate Poisson regression analysis demonstrated that the BZ-exposed workers had significantly increased MN frequency compared with the controls (FR=1.84, 95% CI: 1.56-2.18; P<0.001), and showed a cumulative exposure dose-response relationship. The CYP2E1 rs3813867 mutant allele (CC+GC) (FR 1.15, 95% CI 1.02-1.29; P=0.020) and rs2031920 variant allele (CT+TT) (FR=1.23, 95% CI: 1.09-1.37, P<0.01) was associated with higher MN frequency significantly compared with the wild genotype separately. Furthermore, the MN frequency in rs2031920 variant allele (CT+TT) (FR=1.17, 95% CI: 1.04-1.31, P<0.01) was also higher than the wild genotype when the age, gender and cumulative exposure dose was adjusted in Poisson regression. In addition, the CYP2E1, however, GSTM1null, GSTT1null, GSTP1 rs1695, rs6413432, rs1051740 and rs2234922 polymorphisms showed no association with MN frequency. Our results indicate that two promoter polymorphisms in the CYP2E1 gene, especially the rs2031920 variant allele, were involved with the BZ-induction of MN and may contribute to risk of cancer among exposed workers.
Department of Occupational Health and Toxicology, School of Public Health, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China.
Guang-hui
GH
Zhang
Department of Clinical Laboratory, Wenzhou People's Hospital, 57 Canghou Road, Wenzhou 325000, China.
Ling-li
LL
Ye
Department of Occupational Health and Toxicology, School of Public Health, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China.
Jin-wei
JW
Wang
Department of Epidemiology and Biostatistics, School of Public Health, Xinxiang Medical University, 601 Jinsui Road, Xinxiang 453003, China.
Jing-chao
JC
Ren
Department of Occupational Health and Toxicology, School of Public Health, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China.
Xiao-wen
XW
Xu
Department of Occupational Health and Toxicology, School of Public Health, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China.
Nan-nan
NN
Feng
Department of Occupational Health and Toxicology, School of Public Health, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China.
Li-fang
LF
Zhou
Department of Occupational Health and Toxicology, School of Public Health, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China.
Jian-guo
JG
Ru
Department of Occupational Health and Toxicology, School of Public Health, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China.
Yan-hui
YH
Hao
Department of Occupational Health and Toxicology, School of Public Health, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China.
Wei
W
Tian
Department of Occupational Health and Toxicology, School of Public Health, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China.
Pin
P
Sun
MPH Education Center, Shantou University Medical College, Shantou, Guangdong Province, China.
William W
WW
Au
Environmental & Occupational Medicine & Epidemiology Program, Department of Environmental Health, Harvard School of Public Health, Boston, MA 02115, USA.
David C
DC
Christiani
Department of Occupational Health and Toxicology, School of Public Health, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China. Electronic address: zlxia@shmu.edu.cn.
Zhao-lin
ZL
Xia
D000395:Air Pollutants, Occupational / Q000032:analysis / Q000378:metabolism* / Q000633:toxicity; D001554:Benzene / Q000032:analysis / Q000378:metabolism* / Q000633:toxicity; D002681:China; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics; D004851:Epoxide Hydrolases / Q000235:genetics; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics; D015162:Micronucleus Tests; D016273:Occupational Exposure; D016012:Poisson Distribution; D011110:Polymorphism, Genetic; D012044:Regression Analysis
D000395:Air Pollutants, Occupational; D019392:Cytochrome P-450 CYP2E1; D005982:Glutathione Transferase; D004851:Epoxide Hydrolases; D001554:Benzene
Benzene; CYP2E1; GSTs; Micronuclei; Polymorphism; mEH