Gene promoter methylation in plasma and sputum increases with lung cancer risk
Gene promoter methylation in plasma and sputum increases with lung cancer risk
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DOI：
10.1158/1078-0432.ccr-05-0625
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发表时间：
2005-09-15
影响因子：
11.5
通讯作者：
Picchi, MA
中科院分区：
文献类型：
--
作者：
Belinsky, SA;Klinge, DM;Picchi, MA
目的：肺癌是美国癌症死亡的主要原因，部分原因是缺乏有效的早期发现的有效筛查方法。分别从具有不同肺癌风险的女性的痰和血浆中检测7个和3个基因甲基化的发生率。实验设计：研究人群包括肺癌幸存者(n=56)、临床无癌吸烟者(n=121)和从不吸烟者(n=74)。结果：74名从不吸烟的女性中有10人的血浆DNA中检测到甲基化。肺癌幸存者血浆中p16基因甲基化的发生率最高。与从不吸烟的人相比，肺癌幸存者血浆中至少有一个或多个基因甲基化的几率显著增加(优势比为3.6；95%可信区间为1.9-9.1)。与吸烟者相比，肺癌幸存者痰中O-6-甲基鸟嘌呤-DNA甲基转移酶、ras效应物同源物1、死亡相关蛋白激酶和PAX5α基因甲基化的发生率显著高于吸烟者。与吸烟者相比，肺癌幸存者在痰中三个或更多基因甲基化的几率高6.2倍(95%可信区间，2.1-18.5)。在肺癌存活者中，O-6-甲基鸟嘌呤-DNA甲基转移酶和ras效应物同源物1的甲基化比血浆中更常见，而不是p16。痰中的基因启动子与肺癌风险密切相关。
Purpose: Lung cancer is the leading cause of cancer mortality in the United States, due in part to the lack of a validated and effective screening approach for early detection. The prevalence for methylation of seven and three genes was examined in DNA from sputum and plasma, respectively, from women at different risk for lung cancer.Experimental Design: Lung cancer survivors (n = 56), clinically cancer-free smokers (n = 121), and never smokers (n = 74) comprised the study population. Plasma was collected from all three groups, whereas sputum was collected from lung cancer survivors and smokers.Results: Methylation was detected in plasma DNA from 10 of 74 women who never smoked. Prevalence for methylation of the p16 gene in plasma was highest in lung cancer survivors. Lung cancer survivors showed a significant increase in the odds of having at least one or more genes methylated in plasma (odds ratio, 3.6; 95% confidence interval, 1.9-9.1) than never smokers. The prevalence for methylation of the O-6-methylguanine-DNA methyltransferase, ras effector homologue 1, death associated protein kinase, and PAX5 alpha genes in sputum was significantly higher in lung cancer survivors compared with smokers. Lung cancer survivors had 6.2-fold greater odds (95% confidence interval, 2.1-18.5) for methylation of three or more genes in sputum compared with smokers. Methylation was more commonly detected in sputum than plasma for O-6-methylguanine-DNA methyltransferase and ras effector homologue 1, but not p16, in lung cancer survivors.Conclusion: Concomitant methylation of multiple. gene promoters in sputum is strongly associated with lung cancer risk.