Sun Pin, Qian Ji, Zhang Zhong-Bin, Wan Jun-Xiang, Wu Fen, Jin Xi-Peng, Fan Wei-Wei, Lu Da-Ru, Zhao Nai-Qing, Christiani David C, Xia Zhao-Lin
Department of Occupational Health, School of Public Health, Fudan University, Shanghai, China.
Carcinogenesis. 2008 Dec;29(12):2325-9. doi: 10.1093/carcin/bgn208. Epub 2008 Sep 10.
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.
人们普遍认为，苯的细胞毒性和遗传毒性源于活性代谢产物的作用。因此，代谢酶基因的遗传变异可能导致暴露人群对慢性苯中毒（CBP）的易感性。我们采用病例对照研究，纳入了中国南方268例苯中毒患者和268例职业性接触苯的工人，旨在研究参与代谢I相和II相的基因中的单核苷酸多态性与CBP风险之间的关联。采用TaqMan技术检测CYP1A1、CYP1A2、CYP1B1、ADH1B、EPHX1、EPHX2、NQO1、MPO、GSTP1和UGT1A6基因的多态性。我们还探讨了这些多态性与吸烟和饮酒等生活方式因素之间的潜在相互作用。发现谷胱甘肽S-转移酶pi-1（GSTP1）rs1695多态性与CBP风险之间存在微弱的正相关（P = 0.046），但在对潜在混杂因素进行调整后，这种关联无统计学意义（P = 0.117）。进一步分析表明，携带EPHX1 GGAC/GAGT双倍型（P = 0.00057）或AGAC/GAGT双倍型（P = 0.00086）的受试者CBP风险增加。此外，我们发现携带EPHX1 rs3738047 GA + AA基因型的饮酒者和携带GSTP1 rs1695 AA基因型的不饮酒者更容易受到苯毒性的影响。我们的结果表明，EPHX1基因的遗传多态性可能导致中国职业人群患CBP的风险增加。
