The relationship between COPD and lung cancer.
The relationship between COPD and lung cancer.
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DOI：
10.1016/j.lungcan.2015.08.017
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发表时间：
2015-11
期刊：
影响因子：
--
通讯作者：
Adcock IM
中科院分区：
文献类型：
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作者：
Durham AL;Adcock IM
COPD是肺癌的一个危险因素，超出了他们共同的病因。两者都是由氧化应激驱动的。两者都与细胞老化、衰老和端粒缩短有关。两者都与遗传易感性有关。两者都显示了基因表达的表观遗传调节改变。由于吸烟，COPD和肺癌都是全球主要的健康问题，并且代表了巨大的全球可预防的疾病负担。虽然大多数吸烟者不会患上COPD或肺癌，但它们是密切相关的疾病，作为合并症发生的比率高于吸烟单独引发的比率。肺癌和COPD可能是同一种疾病的不同方面，具有相同的潜在易感性，无论是潜在的遗传易感性、端粒缩短、线粒体功能障碍还是过早衰老。在大多数吸烟者中，吸烟的负担可以通过身体的防御机制来处理：抗氧化剂，如超氧化物歧化酶，抗蛋白酶和DNA修复机制。然而，在这两种疾病的情况下，这些都失败了，如果发生突变就会导致癌症，或者如果对细胞和蛋白质的损害变得太大就会导致COPD。或者，COPD可能是肺癌的驱动因素，通过增加氧化应激和导致的DNA损伤，慢性暴露于促炎细胞因子，抑制DNA修复机制和增加细胞增殖。了解这些疾病患者的原代细胞中驱动这些过程的机制沿着更好的疾病模型对于开发新的治疗方法至关重要。
COPD is a risk factor for lung cancer beyond their shared aetiology. Both are driven by oxidative stress. Both are linked to cellular aging, senescence and telomere shortening. Both have been linked to genetic predisposition. Both show altered epigenetic regulation of gene expression. Both COPD and lung cancer are major worldwide health concerns owing to cigarette smoking, and represent a huge, worldwide, preventable disease burden. Whilst the majority of smokers will not develop either COPD or lung cancer, they are closely related diseases, occurring as co-morbidities at a higher rate than if they were independently triggered by smoking. Lung cancer and COPD may be different aspects of the same disease, with the same underlying predispositions, whether this is an underlying genetic predisposition, telomere shortening, mitochondrial dysfunction or premature aging. In the majority of smokers, the burden of smoking may be dealt with by the body’s defense mechanisms: anti-oxidants such as superoxide dismutases, anti-proteases and DNA repair mechanisms. However, in the case of both diseases these fail, leading to cancer if mutations occur or COPD if damage to the cell and proteins becomes too great. Alternatively COPD could be a driving factor in lung cancer, by increasing oxidative stress and the resulting DNA damage, chronic exposure to pro-inflammatory cytokines, repression of the DNA repair mechanisms and increased cellular proliferation. Understanding the mechanisms that drive these processes in primary cells from patients with these diseases along with better disease models is essential for the development of new treatments.