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肺癌风险的吸烟独立的DNA甲基化标志物:在大型基于人口的队列研究中进行外部验证

Zitong Zhao^1,2, Megha Bhardwaj^1,3, Ziwen Fan¹

¹Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.

|December 3, 2024

概括

这项研究确定了独立于吸烟的特定DNA甲基化位点,可以预测肺癌风险. 五个经验证的表观遗传标记显示出改善肺癌风险分层的潜力.

科学领域:

表观遗传学在表观遗传学中,表观遗传学是指表观遗传学.
癌症流行病学癌症流行病学
基因组学就是基因组学.

背景情况:

吸烟是肺癌的主要危险因素,通常与表观遗传变化有关.
肺癌 (LC) 风险中吸烟独立的表观遗传变化的作用需要进一步研究.

研究的目的:

为了验证之前报告的CpG与LC风险相关的部位,独立于吸烟.
为了评估这些吸烟独立的DNA甲基化标记的预测价值,在一个潜在的队列.

主要方法:

使用的Infinium甲基化EPIC或450KBeadChip测试测量来自德国人口的整体血液中的DNA甲基化 (DNAm).
分析了16个吸烟独立的CpG位点的DNAm水平及其与LC风险的关联,使用危险比率,以包括吸烟状态在内的共变量进行调整.

主要成果:

在17年的时间里,观察到199种肺癌.
特定的CpG部位显示出与LC风险的显著关联:cg02211449 (负关联),cg11385536,cg09736286,cg19907023,cg22032485 (积极关联).
在16个候选CpG地点中,有5个被外部验证为LC风险的预测因素.

结论:

识别并验证了特定的DNA甲基化标记,可独立于吸烟来预测肺癌风险.
这些发现表明,使用表观遗传标志物可以改善肺癌风险分层的潜力.

关键词:

通过DNA甲基化.全表观基因组关联研究 (EWAS)通过外部验证.肺癌的风险肺癌的风险

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