Carcinogenesis Advance Access originally published online on September 10, 2008
Carcinogenesis 2008 29(12):2325-2329; doi:10.1093/carcin/bgn208
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Polymorphisms in phase I and phase II metabolism genes and risk of chronic benzene poisoning in a Chinese occupational population
1 Department of Occupational Health, School of Public Health, Fudan University, Shanghai 200032, China
2 Key Laboratory of Public Health Safety (Fudan University), Ministry of Education, Shanghai 200032, China
3 State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai 200043, China
4 Department of Epidemiology and Statistics, School of Public Health, Fudan University, Shanghai 200032, China
5 Environmental and Occupational Medicine and Epidemiology Program, School of Public Health, Harvard University, Boston, MA, USA
* To whom correspondence should be addressed. Tel/Fax: +86 21 54237050; Email: zlxia{at}shmu.edu.cn
Correspondence may also be addressed to Da-ru Lu. Tel/Fax: +86 21 65642799; Email: drlu{at}fudan.edu.cn
It is widely accepted that the cytotoxicity and genotoxicity of benzene results from the action of reactive metabolites. Therefore, genetic variation in metabolic enzyme genes may contribute to susceptibility to chronic benzene poisoning (CBP) in the exposed population. Using a case–control study that included 268 benzene-poisoned patients and 268 workers occupationally exposed to benzene in South China, we aimed to investigate the association between single-nucleotide polymorphisms in genes with phase I and II of metabolism and risk of CBP. The TaqMan technique was used to detect polymorphisms of CYP1A1, CYP1A2, CYP1B1, ADH1B, EPHX1, EPHX2, NQO1, MPO, GSTP1 and UGT1A6 genes. We also explored potential interactions of these polymorphisms with lifestyle factors such as cigarette smoking and alcohol consumption. A weak positive association was found between glutathione S-transferase pi-1 (GSTP1) rs1695 polymorphism and the risk of CBP (P = 0.046), but this association was not statistically significant (P = 0.117) after adjustment for potential confounders. Further analysis showed that the risk of CBP increased in the subjects with EPHX1 GGAC/GAGT diplotype (P = 0.00057) or AGAC/GAGT diplotype (P = 0.00086). In addition, we found that alcohol drinkers with the EPHX1 rs3738047 GA + AA genotypes and non-alcohol drinkers with the GSTP1 rs1695 AA genotype tended to be more susceptible to benzene toxicity. Our results suggest that genetic polymorphisms in EPHX1 may contribute to risk of CBP in a Chinese occupational population.
Abbreviations: ADH, alcohol dehydrogenase; CBP, chronic benzene poisoning; CI, confidence interval; CYP, cytochrome P450; GSTP1, glutathione S-transferase pi-1; mEH, microsomal epoxide hydrolase; MPO, myeloperoxidase; NQO1, nicotinamide adenine dinucleotide phosphate:quinone oxidoreductase-1; OR, odds ratio; sEH, soluble epoxide hydrolase; SNP, single-nucleotide polymorphism; UGT1A6, uridine 5'-diphospho-glucuronosyltransferase 1A6
These authors contributed equally to this work. Received April 30, 2008; revised September 1, 2008; accepted September 3, 2008.
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