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慢性阻塞性肺疾病和肺癌中的基因组不稳定性:使用微核试验的研究的系统评价和荟萃分析。

Genomic instability in chronic obstructive pulmonary disease and lung cancer: A systematic review and meta-analysis of studies using the micronucleus assay.

机构信息

The Federal Research Center of Coal and Coal Chemistry of SB RAS, Kemerovo, Russia; Research Institute for Complex Issues of Cardiovascular Diseases, Kemerovo, Russia.

Department of Human Sciences and Quality of Life Promotion, San Raffaele University, Rome, Italy; Unit of Clinical and Molecular Epidemiology, IRCCS San Raffaele Pisana, Italy.

出版信息

Mutat Res Rev Mutat Res. 2021 Jan-Jun;787:108344. doi: 10.1016/j.mrrev.2020.108344. Epub 2020 Nov 10.

Abstract

Respiratory tissues are highly susceptible to diseases due to the constant exposure to physical and chemical airborne pollutants. Chronic obstructive pulmonary disease (COPD) and lung cancer are among the most common causes of serious illness and death worldwide. The inflammatory environment associated with these respiratory diseases has long been accepted as the major player in the development of airway abnormalities. The presence and relevance of DNA damage and genomic instability makes the micronucleus assay a suitable candidate to quantitatively estimate these early pathogenetic events. A systematic review and meta-analysis were planned to determine underlying common mechanisms that can explain the relationships between COPD and lung cancer. A total of 17 studies from Jan 1999 to Dec 2019 comparing micronucleus frequency in patients affected by respiratory diseases vs healthy controls were analysed. Our results confirmed the presence of significant association between MN frequency and the diseases investigated, and suggested a circle of events linking inflammation induced oxidative stress to the risk of disease through genomic instability and hypoxia. Therefore, using non-invasive, robust and cost effective genomic instability assays such as the micronucleus assay, would allow us to capture unique phenotypic and biological changes that would allow the identification of subjects at high risk of developing lung diseases and improve early detection strategies.

摘要

由于呼吸组织经常暴露于物理和化学空气污染物中,因此它们极易受到疾病的影响。慢性阻塞性肺疾病(COPD)和肺癌是全球范围内导致严重疾病和死亡的最常见原因之一。与这些呼吸道疾病相关的炎症环境一直被认为是气道异常发展的主要因素。DNA 损伤和基因组不稳定性的存在及其相关性使得微核试验成为定量估计这些早期发病事件的合适候选方法。本研究旨在计划进行系统评价和荟萃分析,以确定能够解释 COPD 和肺癌之间关系的潜在共同机制。分析了 1999 年 1 月至 2019 年 12 月期间共 17 项比较患有呼吸道疾病的患者和健康对照者的微核频率的研究。我们的结果证实了 MN 频率与所研究疾病之间存在显著相关性,并提示了一个事件循环,即炎症诱导的氧化应激通过基因组不稳定性和缺氧导致疾病风险增加。因此,使用非侵入性、稳健且具有成本效益的基因组不稳定性检测方法(如微核试验),可以捕捉到独特的表型和生物学变化,从而识别出患有肺部疾病风险较高的人群,并改善早期检测策略。

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