Carcinogenesis Advance Access published online on September 10, 2008
Carcinogenesis, 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, China; Key Laboratory of Public Health Safety (Fudan University), Ministry of Education, Shanghai, China
2 Institute of Genetics, School of Life Science, Fudan University, Shanghai, China
3 Department of Epidemiology and Statistics, School of Public Health, Fudan University, Shanghai, China
4 Environmental and Occupational Medicine and Epidemiology Program, School of Public Health, Harvard University, Boston, USA
* To whom correspondence should be addressed. Tel (Fax): +86 21 54237050 (Dr. Zhao-lin Xia); E-mail: zlxia{at}shmu.edu.cn, Telephone (Fax): +86 21 65642799 (Dr. Da-ru Lu); E-mail: 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 which 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 (SNPs) 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 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.
The first two authors contributed equally to this work. Received June 10, 2008; revised August 25, 2008; accepted September 1, 2008.
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