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The intriguing association between smoking and reduced melanoma risk

That smoking increases the risk of developing cancer is a widely disseminated public health message, with at least 18 cancer types having a higher incidence in people who smoke than in those who do not. However, paradoxically, smoking appears to protect against the development of melanoma. This issue of the BJD contains a report of the largest study to date that has investigated the association between smoking and melanoma, in which smokers were 30% less likely to develop melanoma than nonsmokers (odds ratio 0 70, 95% confidence interval 0 65–0 76). Despite the limitations of many previous studies, a similar and remarkably consistent reduction of melanoma incidence in smokers has been observed. The effect of smoking on melanoma progression and prognosis is less clear cut. In their study, Gibson et al. found that smokers had a 30% greater overall risk of death compared with nonsmokers (hazard ratio 1 30, 95% confidence interval 1 09–1 55), but there was no significant effect on melanomaspecific survival (MSS). While some recent studies also found that smoking did not influence MSS, others have reported worse MSS in smokers. Reduced overall survival in smokers who develop melanoma is not surprising, given the multiple life-limiting conditions associated with smoking, but the inconsistencies in the reported impact of smoking on MSS are curious. Gibson et al. suggest they may be due to uncontrolled differences in socioeconomic status in previous reports, the consideration of which is a strength of their study. Why is the risk of melanoma reduced in smokers? Answering this question is of great relevance from a public health point of view, as it may have implications for the prevention of melanoma in nonsmokers if the effect could be achieved using a nontoxic component of tobacco smoke. Is it due to an effect of nicotine? This seems likely, probably via an immunological process, as it is known that nicotine modulates immune responses by binding to nicotinic acetylcholine receptors on a variety of immune cells. If the reduction in melanoma risk is indeed due to nicotine rather than some other component of tobacco smoke, the effect should also become apparent in ‘vapers’, who use e-cigarettes for nicotine delivery.