Department of Community Medicine, Faculty of Health Sciences, UiT -the Arctic University of Norway, 9037, Tromsø, Norway.
Department of Computer Science, Norwegian University of Science and Technology, 7491, Trondheim, Norway.
Sci Rep. 2021 Jan 12;11(1):680. doi: 10.1038/s41598-020-80158-8.
Active smoking has been linked to modulated gene expression in blood. However, there is a need for a more thorough understanding of how quantitative measures of smoking exposure relate to differentially expressed genes (DEGs) in whole-blood among ever smokers. This study analysed microarray-based gene expression profiles from whole-blood samples according to smoking status and quantitative measures of smoking exposure among cancer-free women (n = 1708) in the Norwegian Women and Cancer postgenome cohort. When compared with never smokers and former smokers, current smokers had 911 and 1082 DEGs, respectively and their biological functions could indicate systemic impacts of smoking. LRRN3 was associated with smoking status with the lowest FDR-adjusted p-value. When never smokers and all former smokers were compared, no DEGs were observed, but LRRN3 was differentially expressed when never smokers were compared with former smokers who quit smoking ≤ 10 years ago. Further, LRRN3 was positively associated with smoking intensity, pack-years, and comprehensive smoking index score among current smokers; and negatively associated with time since cessation among former smokers. Consequently, LRRN3 expression in whole-blood is a molecular signal of smoking exposure that could supplant self-reported smoking data in further research targeting blood-based markers related to the health effects of smoking.
主动吸烟已被证明与血液中基因表达的调节有关。然而，我们需要更深入地了解，在曾经吸烟的人群中，吸烟暴露的定量测量值与全血中差异表达基因（DEGs）之间的关系。本研究根据吸烟状况和癌症自由女性（n=1708）的吸烟暴露定量测量值，对来自挪威女性和癌症后基因组队列的全血样本进行了基于微阵列的基因表达谱分析。与不吸烟者和前吸烟者相比，当前吸烟者分别有 911 和 1082 个 DEGs，其生物学功能可能表明吸烟对全身的影响。LRRN3 与吸烟状态相关，具有最低的 FDR 调整 p 值。当从未吸烟者和所有前吸烟者进行比较时，没有观察到 DEGs，但当从未吸烟者与戒烟时间不超过 10 年的前吸烟者进行比较时，LRRN3 存在差异表达。此外，LRRN3 与当前吸烟者的吸烟强度、吸烟年限和综合吸烟指数评分呈正相关；与前吸烟者戒烟时间呈负相关。因此，全血中 LRRN3 的表达是吸烟暴露的分子信号，可以替代自我报告的吸烟数据，用于进一步研究与吸烟对健康影响相关的基于血液的标志物。
