Using angiotensin converting enzyme (ACE) inhibitors is associated with an increased risk of lung cancer, especially among people taking the drugs for more than five years, according to a new study in the BMJ.

Researchers followed 992,061 UK patients starting treatment with antihypertensives for a mean of 6.4 years. Over this time, 7,952 people developed lung cancer. After adjusting for confounders, using ACE inhibitors was associated with a 14 per cent increase in the risk of lung cancer compared with angiotensin receptor blockers (1.6 and 1.2 per 1,000 person years respectively).

Lung cancer risk rose from a non-significant 10 per cent increase in those who used ACE inhibitors for five years or less compared with angiotensin receptor blockers, to 22 per cent between five and 10 years and 31 per cent with more than 10 years of use. The latter two increases were significant.

The authors comment that while the associations were “modest”, ACE inhibitors account for about 32 per cent of the 70.1 million antihypertensives dispensed each year in the UK, “thus, small relative effects could translate into large absolute numbers of patients at risk for lung cancer”. They suggest replicating the results, particularly in patients taking ACE inhibitors for longer.

The authors add that the link is “biologically plausible”. ACE inhibitors result in the accumulation of bradykinin and substance P in the lung. Lung cancers and several other malignant tissues seem to express bradykinin receptors. Indeed, bradykinin may directly stimulate growth of lung cancer and promote angiogenesis. Substance P is also expressed in lung cancer and is associated with tumour proliferation and angiogenesis.

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