Estimates of lung cancer among persons who never smoked are 10%–20% in the USA, translating into 20–40 000 cases annually. Globally, and especially in East Asia, the incidence of lung cancer among non-tobacco users is considerably higher than in the USA, especially in women.1 The causes of lung cancer in lifelong never-smokers are not well understood. Possibilities include exposure to other carcinogens such as air pollution, radon, occupational exposures, secondhand tobacco smoke, genetic mutations, infections and hormonal imbalances. A mechanistic explanation may include epigenetic modifications from accumulated DNA damage as part of the ageing process. Some studies have shown that epigenetic age, or DNA methylation markers may be a better indicator of biological age than simple chronological age.2 3 Genes that are silenced, like the tumour suppressor gene p53, can lead to increased cancer risk. DNA methylation, the addition of methyl groups to DNA mainly along sequences, results in silencing of gene expression. Hence, DNA methylation plays an important role in …

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表观遗传时钟作为从不吸烟者肺癌的新时间指针

在美国，从不吸烟的人患肺癌的比例估计为 10%–20%，相当于每年 20–40 000 例。在全球范围内，特别是在东亚，不吸烟者的肺癌发病率远高于美国，尤其是女性。1 终生从不吸烟者患肺癌的原因尚不清楚。可能性包括接触其他致癌物质，如空气污染、氡气、职业接触、二手烟草烟雾、基因突变、感染和荷尔蒙失衡。机械解释可能包括作为衰老过程一部分的累积 DNA 损伤造成的表观遗传修饰。一些研究表明，表观遗传年龄或 DNA 甲基化标记可能比简单的实际年龄更能反映生物年龄。2 3 沉默的基因，如抑癌基因 p53，可能会导致癌症风险增加。 DNA 甲基化（主要沿着序列向 DNA 添加甲基）会导致基因表达沉默。因此，DNA 甲基化在……中起着重要作用。