全面评估吸烟暴露及其与 DNA 甲基化的相互作用。

Comprehensive evaluation of smoking exposures and their interactions on DNA methylation.

机构信息

Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA; Department of Pediatrics, Division of Hematology-Oncology, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA; Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA; Cancer and Hematology Center, Texas Children's Hospital, Houston, TX, USA.

Centre for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway.

出版信息

EBioMedicine. 2024 Feb;100:104956. doi: 10.1016/j.ebiom.2023.104956. Epub 2024 Jan 9.

DOI:10.1016/j.ebiom.2023.104956

PMID:38199042

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10825325/

Abstract

BACKGROUND

Smoking impacts DNA methylation, but data are lacking on smoking-related differential methylation by sex or dietary intake, recent smoking cessation (<1 year), persistence of differential methylation from in utero smoking exposure, and effects of environmental tobacco smoke (ETS).

METHODS

We meta-analysed data from up to 15,014 adults across 5 cohorts with DNA methylation measured in blood using Illumina's EPIC array for current smoking (2560 exposed), quit < 1 year (500 exposed), in utero (286 exposed), and ETS exposure (676 exposed). We also evaluated the interaction of current smoking with sex or diet (fibre, folate, and vitamin C).

FINDINGS

Using false discovery rate (FDR < 0.05), 65,857 CpGs were differentially methylated in relation to current smoking, 4025 with recent quitting, 594 with in utero exposure, and 6 with ETS. Most current smoking CpGs attenuated within a year of quitting. CpGs related to in utero exposure in adults were enriched for those previously observed in newborns. Differential methylation by current smoking at 4-71 CpGs may be modified by sex or dietary intake. Nearly half (35-50%) of differentially methylated CpGs on the 450 K array were associated with blood gene expression. Current smoking and in utero smoking CpGs implicated 3049 and 1067 druggable targets, including chemotherapy drugs.

INTERPRETATION

Many smoking-related methylation sites were identified with Illumina's EPIC array. Most signals revert to levels observed in never smokers within a year of cessation. Many in utero smoking CpGs persist into adulthood. Smoking-related druggable targets may provide insights into cancer treatment response and shared mechanisms across smoking-related diseases.

FUNDING

Intramural Research Program of the National Institutes of Health, Norwegian Ministry of Health and Care Services and the Ministry of Education and Research, Chief Scientist Office of the Scottish Government Health Directorates and the Scottish Funding Council, Medical Research Council UK and the Wellcome Trust.

摘要

背景

吸烟会影响 DNA 甲基化，但缺乏关于性别或饮食摄入、近期戒烟（<1 年）、胎儿期吸烟暴露导致的甲基化差异持续存在以及环境烟草烟雾（ETS）相关的吸烟相关差异甲基化的相关数据。

方法

我们对来自 5 个队列的多达 15014 名成年人进行了荟萃分析，这些队列的血液 DNA 甲基化使用 Illumina 的 EPIC 芯片进行测量，用于当前吸烟（2560 人暴露）、戒烟<1 年（500 人暴露）、胎儿期（286 人暴露）和 ETS 暴露（676 人暴露）。我们还评估了当前吸烟与性别或饮食（纤维、叶酸和维生素 C）的相互作用。

结果

使用错误发现率（FDR<0.05），65857 个 CpG 与当前吸烟有关，4025 个与近期戒烟有关，594 个与胎儿期暴露有关，6 个与 ETS 有关。大多数与当前吸烟相关的 CpG 在戒烟一年内会减弱。在成年人中与胎儿期暴露相关的 CpG 丰富了以前在新生儿中观察到的 CpG。当前吸烟在 4-71 个 CpG 上的甲基化差异可能受到性别或饮食摄入的影响。近一半（35-50%）450 K 芯片上的差异甲基化 CpG 与血液基因表达相关。当前吸烟和胎儿期吸烟 CpG 涉及 3049 和 1067 个可药物靶点，包括化疗药物。