中国呼吸与危重监护杂志

中国呼吸与危重监护杂志

慢性黏液分泌过多与痰中肿瘤抑制基因启动子甲基化水平的相关性分析

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目的 研究吸烟者痰液 DNA 中的肿瘤抑制基因,评估慢性黏液分泌过多(CMH)与痰中基因启动子甲基化的相关性。 方法 纳入 2013 年至 2016 年延安大学附属医院呼吸内科诊治的患者,使用甲基化特异性(MSP)方法评估 700 例城市吸烟者和 380 例农村吸烟者痰样品中 11 个肿瘤抑制基因的启动子甲基化水平。 结果 CMH 与甲基化基因的总体增加的数量显著相关,其中硫酸酯酶 2(SULF2)甲基化表现出最一致的相关性。SULF2 甲基化和 CMH 之间的关联在两组吸烟者男性中显著增加(OR=2.73,95%CI 1.53~4.93,P=0.001;OR=2.96,95%CI 1.47~5.94,P=0.002),但在女性中不显著。与目前吸烟者比较,具有持续性 CMH 的男性曾经吸烟者中甲基化水平与 CMH 之间的关联更为明显(SULF2OR=3.64,95%CI 1.57~8.35,P=0.002)。 结论 具有持续性 CMH 的男性前吸烟者痰液细胞中肺癌风险基因的启动子甲基化水平显著增加,可能会增加患肺癌的风险。

Objective To investigate the tumor suppressor genes of phlegm DNA in smokers, and analyze the correlation between methylation level of tumor suppressor gene promoter and chronic mucus hypersecretion (CMH). Methods The study recruited the patients who were admitted in the respiratory department during 2013-2016 in this hospital, including 700 cases of urban smokers and 380 cases of rural smokers. Eleven genes commonly silenced by promoter methylation in lung cancer and associated with cancer risk were selected. Methylation specific PCR (MSP) was used in the sputum sample of 700 individuals in the urban smokers cohort. Replication was performed in 380 individuals from the rural smokers cohort. Results CMH was significantly associated with an overall increased number of methylated genes, with SULF2 methylation demonstrating the most consistent association. The association between SULF2 methylation and CMH was significantly increased in males but not in females both in the urban and rural groups (OR=2.73, 95%CI 1.53-4.93, P=0.001; OR=2.96, 95%CI 1.47-5.94, P=0.002, respectively). Furthermore, the association between methylation and CMH was more obvious among 139 male former smokers with persistent CMH compared with current smokers (SULF2, OR=3.64, 95%CI 1.57-8.35, P=0.002). Conclusion These findings demonstrate that especially male former smokers with persistent CMH have markedly increased promoter methylation of lung cancer risk genes and potentially could be at increased risk for lung cancer.

关键词: 基因启动子的甲基化; 慢性黏液分泌过多; 肺癌基因

Key words: Methylation of gene promoters; Chronic mucus hypersecretion; Lung cancer genes

引用本文: 彭丹, 刘东利, 贺小龙. 慢性黏液分泌过多与痰中肿瘤抑制基因启动子甲基化水平的相关性分析. 中国呼吸与危重监护杂志, 2018, 17(1): 27-32. doi: 10.7507/1671-6205.201704007 复制

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