Chen Bo, Hu Yunping, Jin Taiyi, Lu Daru, Shao Minhua, Zheng Lixing, Wang Qiangyi, Shen Yue, Liu Hongliang, Liu Yanhong, Zhou Yuanfen
Department of Occupational Health and Toxicology, School of Public Health, Fudan University, Shanghai, 200032, PR China.
Sci Total Environ. 2007 Aug 1;381(1-3):38-46. doi: 10.1016/j.scitotenv.2007.02.021. Epub 2007 May 11.
Urinary 1-hydroxypyrene (1-OHP), a biomarker of polycyclic aromatic hydrocarbons (PAHs) exposure, may be influenced by metabolic gene polymorphisms. Such knowledge could benefit us in understanding the inter-individual difference in the mechanism of PAHs-induced carcinogenesis. We investigated the influence of gene polymorphisms on urinary 1-OHP concentrations in 447 coke oven workers from two coking plants in south China. After adjustment for age, plant, level of occupational exposure, body mass index, level of education, alcohol consumption, cigarette smoking and respirator usage, AhR R554K (rs2066853), UGT1A1 -3263T>G (rs4124874) and GSTP1 I105V (rs1695) were associated with urinary 1-OHP excretion with the p-value of 0.053, 0.006 and 0.021, respectively. The concentrations of urinary 1-OHP (Geometric mean, micromol/mol creatinine) in the homozygous major variant carriers and homozygous minor variant carriers for AhR R554K, UGT1A1 -3263T>G and GSTP1 I105V were listed as follows: 4.20 and 5.12, 5.11 and 3.92, 4.93 and 2.91, respectively. GSTT1 present carriers had a significantly higher urinary 1-OHP level than that in null carriers in the case with AhR R554K GA/AA carriers (5.17 vs. 3.64 micromol/mol creatinine, p=0.038), as well as in the case with UGT1A1 -3263T>G TG/GG carriers (5.67 vs. 3.38 micromol/mol creatinine, p=0.001). These results showed that AhR, UGT1A1, GSTP1 and GSTT1 polymorphisms were associated with urinary 1-OHP concentrations in Chinese coke oven workers. No influence was found in the association between urinary 1-OHP and other genetic polymorphisms such as CYP1A1, CYP1A2, CYP1B1, CYP2E1, EPHX1, EPHX2 in this population.
尿中1-羟基芘(1-OHP)是多环芳烃(PAHs)暴露的生物标志物,可能受代谢基因多态性影响。此类知识有助于我们理解PAHs致癌机制中的个体差异。我们调查了中国南方两家焦化厂447名焦炉工人的基因多态性对尿中1-OHP浓度的影响。在调整年龄、工厂、职业暴露水平、体重指数、教育程度、饮酒量、吸烟情况和呼吸器使用情况后,芳烃受体(AhR)R554K(rs2066853)、尿苷二磷酸葡萄糖醛酸基转移酶1A1(UGT1A1)-3263T>G(rs4124874)和谷胱甘肽S-转移酶P1(GSTP1)I105V(rs1695)与尿中1-OHP排泄相关,p值分别为0.053、0.006和0.021。AhR R554K、UGT1A1 -3263T>G和GSTP1 I105V的纯合主要变异携带者和纯合次要变异携带者的尿中1-OHP浓度(几何均值,微摩尔/摩尔肌酐)如下:分别为4.20和5.12、5.11和3.92、4.93和2.9。在AhR R554K GA/AA携带者中(5.17对3.64微摩尔/摩尔肌酐,p = 0.038)以及在UGT1A1 -3263T>G TG/GG携带者中(5.67对3.38微摩尔/摩尔肌酐,p = 0.001),GSTT1存在携带者的尿中1-OHP水平显著高于缺失携带者。这些结果表明,AhR、UGT1A1、GSTP1和GSTT1多态性与中国焦炉工人尿中1-OHP浓度相关。在该人群中未发现尿中1-OHP与其他基因多态性如细胞色素P450 1A1(CYP1A1)、细胞色素P450 1A2(CYP1A2)、细胞色素P450 1B1(CYP1B1)、细胞色素P450 2E1(CYP2E1)、环氧化物水解酶1(EPHX1)、环氧化物水解酶2(EPHX2)之间的关联有影响。