PO.PS01.01 · 人群科学
危地马拉不吸烟女性接触固体燃料燃烧与鼻上皮转录组变化
Exposure to solid fuel burning and transcriptomic changes in the nasal epithelium in never smoking women in Guatemala
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摘要 Abstract
中文摘要
引言：了解与环境暴露相关的基因表达改变，有助于洞察它们如何促成癌症风险。我们此前表明，暴露于柴油发动机尾气（DEE）或烟煤的个体的基因表达变化与吸烟者的变化存在重叠，提示存在共同的毒性机制。木烟由生物质燃料的不完全燃烧产生，被归类为可能致癌物（2A 组），但对其基因表达效应的研究有限。在此，我们开展了一项试点研究，以检验与吸烟、DEE 和烟煤暴露相关的基因是否在暴露于木烟的个体中也存在差异表达。方法：我们研究了家庭空气污染干预网络试验中来自危地马拉的 16 名以木材为主要燃料的不吸烟女性。使用监测仪测量 PM2.5 暴露，并评估尿液 1-羟基芘（1-OHP）作为多环芳烃暴露的生物标志物。鼻甲刷样本进行了 bulk RNA-seq，并通过基于 GTEx 的流程处理。使用 limma 进行差异表达（DE）分析以比较高与低 PM2.5 和 1-OHP。采用基因集富集分析评估先前报道的与吸烟、DEE 暴露和烟煤使用相关的基因特征是否在按 t 统计量排序的每种暴露的上调和下调基因中富集。结果：我们发现，上调和下调的吸烟相关特征均在 PM2.5 水平高的木烟暴露女性中一致富集（分别 p = 0.001 和 p = 0.04），以及在 1-OHP 水平升高的女性中富集（分别 p < 0.001 和 p = 0.015）。与烟煤和 DEE 暴露相关的下调基因在 PM2.5 水平高的参与者中也受到抑制（烟煤特征 p = 0.005）以及 1-OHP（烟煤和 DEE 特征分别 p < 0.001 和 p = 0.008）。值得注意的是，这些特征包括 CYP1A1、CYP1B1 和 CDH1 等基因，它们参与致癌物的活化和解毒。结论：不吸烟者的木烟暴露与气道基因表达变化相关，这些变化与吸烟、DEE 和烟煤相关的变化相似，提示对燃烧污染物存在共同的分子反应，以及与肺癌发生相关的通路。需要更大规模的研究来重复这些发现，并进一步研究生物质烟雾在肺癌发生中的作用。
查看英文原文 English abstract
Introduction Understanding environmental-exposure associated gene expression alterations provides insights into how they contribute to cancer risk. We previously showed that individuals exposed to diesel engine exhaust (DEE) or smoky coal exhibit gene expression changes overlapping with those of smokers, suggesting shared mechanisms of toxicity. Wood smoke, produced by incomplete combustion of biomass fuels, is classified as probably carcinogenic (Group 2A), yet studies of its gene expression effects are limited. Here, we conducted a pilot study to examine whether genes associated with smoking, DEE, and smoky coal exposure are also differentially expressed in individuals exposed to wood smoke. Methods We studied 16 never-smoking women from Guatemala in the Household Air Pollution Intervention Network trial who use wood as their primary fuel. PM 2.5 exposure was measured with monitors, and urinary 1-Hydroxypyrene (1-OHP) was assessed as a biomarker of polycyclic aromatic hydrocarbons exposure. Nasal turbinate brush samples underwent bulk RNA-seq and were processed via a GTEx-based pipeline. Differential expression (DE) analysis to compare high vs. low PM 2.5 and 1-OHP was conducted using limma. Gene Set Enrichment Analysis was used to evaluate whether previously reported gene signatures associated with smoking, DEE exposure, and smoky coal use, were enriched among genes up- and down-regulated for each exposure, ranked by t-statistics. Results We found that both up-regulated and down-regulated smoking-associated signatures were concordantly enriched in wood smoke exposed women with high levels of PM₂.₅ (p = 0.001 and p=0.04, respectively) and among women with elevated 1-OHP levels (p < 0.001 and p = 0.015, respectively). Genes down-regulated with exposure to smoky coal and DEE were also suppressed in participants with high levels of PM 2.5 (p=0.005 for smoky coal signature) and 1-OHP (p<0.001 & p=0.008 for smoky coal and DEE signatures, respectively). Notably, the signatures included genes such as CYP1A1, CYP1B1, and CDH1, which are involved in activation and detoxification of carcinogens. Conclusions Wood smoke exposure in never smokers was associated with airway gene expression changes with similarities to those associated with smoking, DEE, and smoky coal, suggesting shared molecular response to combustion pollutants and pathways linked to lung cancer development. Larger studies are needed to replicate these findings and further examine biomass smoke in lung carcinogenesis.
利益披露 Disclosure
B. Blechter, None..
L. Yu, None..
K. Salmons, None..
M. Clarke, None..
D. Barr, None..
K. Steenland, None.