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 a variety of biological …