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目的分析焦炉工人周围血细胞中p16基因启动子区CpG岛异常甲基化状态,寻找焦炉工人肺癌辅助筛查的生物标志物。方法以74名男性焦炉工人为接触组,以47名供水厂男性职工为对照组。采集2组人员的班后尿,用高效液相色谱法检测其内暴露指标1-羟基芘(1-OH-Py)的水平;同时采集晨起空腹肘静脉血,分离周围血单个核细胞,用彗星实验检测DNA损伤情况;并提取基因组DNA,用甲基化特异性聚合酶链反应技术检测p16基因启动子区CpG岛甲基化发生情况。结果接触组尿1-OH-Py水平[(0.46±0.12)μmol/mol Cr]和DNA拖尾的Olive尾距[(0.41±0.25)μm]高于对照组[(0.17±0.06)μmol/mol Cr、(0.32±0.12)μm],差异有统计学意义(P<0.05)。接触组p16基因的异常甲基化的检出率(36.49%)高于对照组(4.26%),差异有统计学意义(P<0.01);并且p16基因的异常甲基化检出率随着尿1-OH-Py的水平升高逐渐增加,差异有统计学意义(P<0.01)。结论周围血p16基因异常甲基化可能是焦炉工人肺癌早期筛查有效的生物标志物。
Objective To analyze the abnormal methylation status of CpG island in promoter region of p16 gene in blood cells around coke oven workers, and to find biomarkers for secondary screening of lung cancer in coke oven workers. Methods Totally 74 male coke oven workers were used as the exposure group and 47 male workers of the water supply factory were used as the control group. The urine samples were collected from two groups of patients. The level of 1-OH-Py, the indicator of exposure, was detected by high performance liquid chromatography (HPLC). Meanwhile, fasting elbow venous blood was harvested at the same time. Peripheral blood mononuclear cells DNA damage was detected by comet assay. Genomic DNA was extracted and the methylation of CpG island in promoter region of p16 gene was detected by methylation-specific polymerase chain reaction (PCR). Results Compared with the control group [(0.17 ± 0.06) μmol / mol [(0.46 ± 0.12) μmol / mol Cr] and DNA tailing Olive tail [ Cr, (0.32 ± 0.12) μm], the difference was statistically significant (P <0.05). The detection rate of abnormal methylation of p16 gene in contact group (36.49%) was higher than that in control group (4.26%), the difference was statistically significant (P <0.01); and the detection rate of abnormal methylation of p16 gene was Urine 1-OH-Py levels increased gradually, the difference was statistically significant (P <0.01). Conclusion The abnormal methylation of p16 gene in peripheral blood may be an effective biomarker for early screening of lung cancer in coke oven workers.