Oral Epithelium as a Surrogate Tissue for Assessing Smoking-Induced Molecular Alterations in the Lungs
Oral Epithelium as a Surrogate Tissue for Assessing Smoking-Induced Molecular Alterations in the Lungs
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DOI：
10.1158/1940-6207.capr-08-0058
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发表时间：
2008-06-01
影响因子：
3.3
通讯作者：
Mao, Li
中科院分区：
文献类型：
--
作者：
Bhutani, Manisha;Pathak, Ashutosh Kumar;Mao, Li
吸烟者的肺部和口腔暴露于烟草致癌物质。我们假设烟草引起的口腔上皮分子改变与肺部的分子改变相似，因此口腔上皮可以用作评估肺部改变的替代组织。我们使用甲基化特异性 PCR 分析了基线时和干预后 3 个月时 p16 和 FHIT 基因的启动子甲基化情况，对来自 127 名吸烟者的 1,774 份口腔和支气管刷标本进行了随机安慰剂对照化学预防试验。以盲法分析口腔组织甲基化模式与支气管甲基化指数（每个受试者的甲基化位点/总位点）之间的关联。基线时，23% 的 p16 样本中存在支气管组织启动子甲基化，17% 的 FHIT 样本中存在启动子甲基化，35% 的 p16 和 FHIT 样本中存在启动子甲基化；这些百分比与口腔组织中的甲基化相当：19% (p16)、15% (FHIT) 和 31%（p16 和 FHIT）。来自 125 名个体的口腔和支气管组织的数据均可用，其中两个位点的改变密切相关（p16 和 FHIT 的 P < 0.0001）。基线时，口腔组织甲基化患者（两个基因中的任何一个；39 名患者）的平均支气管甲基化指数远高于无口腔组织甲基化的患者（86 名患者）：0.53 +/- 0.29 与 0.27 + 0.26 甲基化指数（P < 0.0001）。干预后 3 个月也出现类似的相关性。我们的研究结果支持口腔上皮作为评估烟草引起的肺部分子损伤的替代组织的潜力，因此对于设计未来的肺癌预防试验以及肺癌风险和早期检测的研究具有重要意义。
The lungs and oral cavity of smokers are exposed to tobacco carcinogens. We hypothesized that tobacco-induced molecular alterations in the oral epithelium are similar to those in the lungs, and thus the oral epithelium may be used as a surrogate tissue for assessing alterations in the lungs. We used methylation-specific PCR to analyze promoter methylation of the p16 and FHIT genes at baseline and 3 months after intervention in 1,774 oral and bronchial brush specimens from 127 smokers enrolled in a randomized placebo-controlled chemoprevention trial. The association between methylation patterns in oral tissues and bronchial methylation indices (methylated sites/total sites per subject) was analyzed in a blinded fashion. At baseline, promoter methylation in bronchial tissue was present in 23% of samples for p16, 17% for FHIT, and 35% for p16 and FHIT; these percentages were comparable to methylation in oral tissue: 19% (p16), 15% (FHIT), and 31% (p16 and FHIT). Data from both oral and bronchial tissues were available for 125 individuals, in whom the two sites correlated strongly with respect to alterations (P < 0.0001 for both p16 and FHIT). At baseline, the mean bronchial methylation index was far higher in patients with oral tissue methylation (in either of the two genes; 39 patients) than in patients without oral tissue methylation (86 patients): 0.53 +/- 0.29 versus 0.27 + 0.26 methylation index (P < 0.0001). Similar correlations occurred at 3 months after intervention. Our results support the potential of oral epithelium as a surrogate tissue for assessing tobacco-induced molecular damage in the lungs and thus have important implications for designing future lung cancer prevention trials and for research into the risk and early detection of lung cancer.