焦炉作业工人外周血淋巴细胞染色体损伤的遗传易感性研究

目的研究外源性化学物代谢酶基因多态性与焦炉作业工人外周血淋巴细胞染色体损伤的关系。方法选取149名焦炉作业工人和24名非职业多环芳烃(PAH)暴露人员作为研究对象,测定其尿中1-羟基芘浓度来反映PAH暴露的内剂量;对照组的外周血淋巴细胞微核水平的上4分位数(6‰)作为判断个体染色体损伤阳性的界值;分析CYP1A1、GSTM1、GSTT1、GSTP1、CYP2E1、NQO1、NAT2和mEH基因的多态性;使用多元logistic回归方程校正职业暴露情况、年龄、性别、吸烟和饮酒状况因素,计算不同基因型工人发生染色体损伤阳性的OR值,并探讨基因间的交互作用。结果调整了173名研究对象的职业暴露、年龄、性别、吸烟和饮酒状况后,GSTM1缺失基因型个体染色体损伤危险度显著性增加(调整OR=2．01,95％CI=1．03—3.91);与NQO1基因P187S位点野生型纯合子个体比较,变异型纯合子个体染色体损伤危险度显著性增加(调整OR=3．18,95％CI=1．18—8．62);与mEH基因H113Y位点野生型纯合子个体比较,变异型纯合子个体染色体损伤危险度显著性降低(调整OR=0．40,95％CI=0.19～0．88);未发现其他基因的遗传变异与研究对象外周血淋巴细胞染色体损伤危险度的显著关联。此外,还发现GSTM1、NQO1基因P187S位点和mEH基因H113Y位点的遗传变异对染色体损伤危险度的影响中存在基因-基因交互作用。结论本研究发现GSTM1、NQO1和mEH基因的遗传变异可显著性影响职业PAH暴露个体外周血淋巴细胞染色体损伤危险度,并存在基因一基因交互作用。

A study on the inherited susceptibility of chromosomal damage in peripheral blood lymphocytes among coke oven workers

OBJECTIVE: To investigate the association between polymorphisms of metabolic enzyme genes and chromosomal damage risk in peripheral blood lymphocytes among coke oven workers. METHODS: One hundred and fourty-nine coke oven workers and 24 referents without occupational polycyclic aromatic hydrocarbons (PAH) exposure were recruited in this study. Urinary 1-hydroxypyrene levels were measured as the internal dose of PAH exposure. The 6 per 1 000 of micronucleus value was used as the cut-off value to determine whether the individual's chromosomal damage was positive. The genotypes of CYP1A1, GSTM1, GSTT1, GSTP1, CYP2E1, NQO1, NAT2 and mEH genes were determined by PCR-based methods. Multiple logistic regression was used to calculate the adjusted ORs and the 95% CI for the risk of chromosomal damage and to analyze the gene-gene interaction. RESULTS: In 173 subjects, after adjusting the occupational exposure, age, sex, smoking and drinking status, the subjects with GSTM1 null genotype have significantly higher risk for chromosomal damage than subjects with GSTM1 positive genotype (adjusted OR = 2.01, 95% CI = 1.03 -3.91). Compared with the wild homozygotes at P187S site of NQO1 gene, the variant homozygotes have significantly higher risk for chromosomal damage (adjusted OR = 3.18, 95% CI = 1.18 - 8.62). The subjects with variant allele at H113Y site of mEH gene have significantly lower risk for chromosomal damage (adjusted OR = 0.40, 95% CI = 0.19 - 0.88). No significant associations were found for other gene polymorphisms and chromosomal damage risk. In addition, the gene-gene interactions were also found among GSTM1, NQO1 gene P187S and mEH gene H113Y polymorphisms for the risk of chromosomal damage risk. CONCLUSION: Significant associations between genetic polymorphisms in GSTM1, NQO1 and mEH gene and risk for chromosomal damage were found among occupational PAH-exposed workers, which related to the mechanism of PAH carcinogenesis.