Promoter hypermethylation of multiple genes in sputum precedes lung cancer incidence in a high-risk cohort
Promoter hypermethylation of multiple genes in sputum precedes lung cancer incidence in a high-risk cohort
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DOI：
10.1158/0008-5472.can-05-3408
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发表时间：
2006-03-15
期刊：
影响因子：
11.2
通讯作者：
Byers, T
中科院分区：
文献类型：
--
作者：
Belinsky, SA;Liechty, KC;Byers, T
一种敏感的肺癌筛查方法可以显着降低这种疾病的高死亡率。先前的研究表明，肺癌诊断前痰液脱落细胞中存在基因启动子甲基化。本研究的目的是对来自极高危队列的肺癌病例进行巢式病例对照研究，以评估痰液中14个基因的启动子甲基化。对照组（n = 92）是按性别、年龄和入组月份与病例（n = 98）匹配的队列成员。对诊断前18个月内和> 18个月内收集的近端痰液进行比较，发现基因启动子甲基化的患病率随着肺癌诊断时间的缩短而增加。14个基因中有6个与肺癌风险增加> 50%相关。这6个基因中有3个或3个以上同时发生甲基化与风险增加6.5倍相关，敏感性和特异性为64%。这是第一项前瞻性研究了大量基因预测肺癌的能力，并显示了痰液中基因启动子高甲基化作为识别癌症发病高风险人群的分子标志物的前景。
A sensitive screening approach for lung cancer could markedly reduce the high mortality rate for this disease. Previous studies have shown that methylation of gene promoters is present in exfoliated cells within sputum prior to lung cancer diagnosis. The purpose of the current study is to conduct a nested case-control study of incident lung cancer cases from an extremely high-risk cohort for evaluating promoter methylation of 14 genes in sputum. Controls (n = 92) were cohort members matched to cases (n = 98) by gender, age, and month of enrollment. The comparison of proximal sputum collected within 18 months to > 18 months prior to diagnosis showed that the prevalence for methylation of gene promoters increased as the time to lung cancer diagnosis decreased. Six of 14 genes were associated with a > 50% increased lung cancer risk. The concomitant methylation of three or more of these six genes was associated with a 6.5-fold increased risk and a sensitivity and specificity of 64%. This is the first study to prospectively examine a large panel of genes for their ability to predict lung cancer and shows the promise of gene promoter hypermethylation in sputum as a molecular marker for identifying people at high risk for cancer incidence.