Gene-expression profiling of buccal epithelium among non-smoking women exposed to household air pollution from smoky coal.

Gene-expression profiling of buccal epithelium among non-smoking women exposed to household air pollution from smoky coal.
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DOI:
10.1093/carcin/bgv150
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发表时间:
2015-08
期刊:
影响因子:
4.7
通讯作者:
Teresa W. Wang;R. Vermeulen;Wei Hu;Gang Liu;Xiaohui Xiao;Y. Alekseyev;Jun Xu;B. Reiss;K. Steiling;G. Downward;D. Silverman;F. Wei;Guoping Wu;Jihua Li;M. Lenburg;N. Rothman;A. Spira;Q. Lan
Teresa W. Wang;R. Vermeulen;Wei Hu;Gang Liu;Xiaohui Xiao;Y. Alekseyev;Jun Xu;B. Reiss;K. Steiling;G. Downward;D. Silverman;F. Wei;Guoping Wu;Jihua Li;M. Lenburg;N. Rothman;A. Spira;Q. Lan
中科院分区:
医学2区
文献类型:
--
作者:
Teresa W. Wang;R. Vermeulen;Wei Hu;Gang Liu;Xiaohui Xiao;Y. Alekseyev;Jun Xu;B. Reiss;K. Steiling;G. Downward;D. Silverman;F. Wei;Guoping Wu;Jihua Li;M. Lenburg;N. Rothman;A. Spira;Q. Lan

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在宣威和抚远等中国农村县,肺癌发病率是世界上最高的。虽然与无烟煤(无烟煤)相比,这一人群的疾病风险升高与使用无烟煤(烟煤)有关,但与这种接触相关的潜在分子变化仍不清楚。为了了解煤烟暴露的生理效应,我们分析了宣威和抚远健康非吸烟女性居民燃烧煤烟(n = 26)和无烟煤(n = 9)的颊上皮细胞全基因组基因表达谱。通过微阵列分析基因表达,与煤类型相关的变化与家庭细颗粒物(PM2.5)和多环芳烃(PAHs)水平相关。282个基因的表达水平在有烟煤暴露与无烟煤暴露之间发生了改变(P < 0.005),包括促炎性IL 8的2倍增加和促凋亡CASP 3的减少。该特征与致癌多环芳烃(例如苯并[a]芘; r = 0.41)的相关性高于与非致癌多环芳烃(例如芴; r = 0.08)或PM2.5(r = 0.05)的相关性。在吸烟者和非吸烟者的口腔活检中,吸烟煤暴露改变的基因与烟草暴露一致地富集(GSEA,q < 0.05)。这是第一项确定与煤烟暴露相关的颊上皮基因表达特征的研究,这在一定程度上类似于对烟草烟雾的分子反应,从而为先前将这种暴露与肺癌风险联系起来的流行病学研究提供了生物相容性。
In China's rural counties of Xuanwei and Fuyuan, lung cancer rates are among the highest in the world. While the elevated disease risk in this population has been linked to the usage of smoky (bituminous) coal as compared to smokeless (anthracite) coal, the underlying molecular changes associated with this exposure remains unclear. To understand the physiologic effects of smoky coal exposure, we analyzed the genome-wide gene-expression profiles in buccal epithelial cells collected from healthy, non-smoking female residents of Xuanwei and Fuyuan who burn smoky (n = 26) and smokeless (n = 9) coal. Gene-expression was profiled via microarrays, and changes associated with coal type were correlated to household levels of fine particulate matter (PM2.5) and polycyclic aromatic hydrocarbons (PAHs). Expression levels of 282 genes were altered with smoky versus smokeless coal exposure (P < 0.005), including the 2-fold increase of proinflammatory IL8 and decrease of proapoptotic CASP3. This signature was more correlated with carcinogenic PAHs (e.g. Benzo[a]pyrene; r = 0.41) than with non-carcinogenic PAHs (e.g. Fluorene; r = 0.08) or PM2.5 (r = 0.05). Genes altered with smoky coal exposure were concordantly enriched with tobacco exposure in previously profiled buccal biopsies of smokers and non-smokers (GSEA, q < 0.05). This is the first study to identify a signature of buccal epithelial gene-expression that is associated with smoky coal exposure, which in part is similar to the molecular response to tobacco smoke, thereby lending biologic plausibility to prior epidemiological studies that have linked this exposure to lung cancer risk.