Reacción a "Reactions: e-cigarettes may cause epigenetic changes associated with cancer even in the short term"

This international study used a relatively large number of samples (N>3,500), collected from different sites (saliva, blood, cervix) and comprising different cell types (epithelial, immune and lymphoid), to assess epigenetic changes that may be associated with cancer development. The study included current, ex- and never smokers, and also included a subsample of vapers (N=116) who had never regularly smoked cigarettes. 
This comprehensive analysis confirms well-known epigenetic changes associated with smoking observed in blood, extending this to saliva and specific cell types, as well as identifying novel associations with cigarette smoking, which are also seen in separate cancer tissue and early lesion samples. Crucially, some of the epigenetic changes were also observed in saliva samples from vapers, albeit to a lesser extent and not across all cell types.
While this study provides useful information about potential corollaries of e-cigarette use also seen with cigarettes, which need to be studied further, in my mind this does not provide proof that e-cigarettes cause cancer for several reasons: 

1. It is difficult to assess the extent to which the changes seen here translate into actual cancer development. Most cancers involve complex multicellular and multistep processes involving different biological systems, which can include epigenetic changes. However, these alone are unlikely to tell the whole story. 
2. The changes reported here are based on differences seen in smokers, some of which are also replicated in a smaller group of vapers. However, such similarities could be the result of confounding (e.g., if vapers are more likely to engage in a variety of unmeasured harmful behaviours that may drive epigenetic change seen in smokers). This study did not assess or control for this kind of confounding, which is compounded by the fact that the participants from the different datasets used here provided samples from different sites and likely varied in important characteristics. 
3. Because the group of vapers studied was relatively small, it was not possible to link epigenetic changes to vaping exposure in a clear dose-response manner. While the authors looked at vaping duration, there is only limited evidence that longer duration was associated with greater changes. 
4. The paper does not assess epigenetic changes unique to e-cigarettes but looked at those seen in smokers. This is of importance as we already know that e-cigarettes, compared with cigarettes, expose users to much lower levels of known tobacco-related carcinogens that drive cancer (in part because e-cigarettes do not involve combustion, which generates high levels of harmful chemicals seen in tobacco smoke). This means that the health consequences (and underlying causative processes) of e-cigarette use may be quite distinct from those of cigarettes use. These e-cigarette-specific changes need to be investigated in their own right.

Notwithstanding these limitations, the findings in this paper highlight the continued need to elucidate the potential impact of vaping on disease, including assessing effects distinct from tobacco exposure. It is important to remember that e-cigarettes are a harm reduction product, not a risk-free product, aimed at those using uniquely harmful cigarettes. This paper does not change this risk calculus and serves to underscore the CMO's advice: ‘if you smoke, vaping is much safer; if you don't smoke, don't vape’.