© Journal of Thoracic Disease. All rights reserved. J Thorac Dis 2018; 10 (Suppl 26): S3084-S3087 jtd. amegroups. com (of birth) revealed a failure of aspirin if born under Gemini and Libra (11). In addition, in other large trials, therapy appears to work in some countries and not others. The practice of subset analysis, however, has not gone away and is given respectability by calling the analysis exploratory or hypothesis generating. The Cantos lung cancer analysis is in this category and interpreting the importance of the observation is based on the plausibility of the effect seen being real. Such plausibility, which argues against the playof-chance, relies on issues of study size and event number as well as the biology.

Cantos was a large study, selecting patients who had a hs-CRP≥ 2. It was performed in individuals who had a history of prior myocardial infarction and, therefore, enriched (without intent) for current or previous smokers. One would expect, therefore, that if there is an anti-cancer effect it would be seen in a smoking-associated tumour. Nonetheless there were only 129 new cases of lung cancer out of 10,061 over a period of 3.7 years. The effect was only seen in lung cancer and not non-lung cancer. Plausibility is added though by the apparent dose-effect relationship, arguably stronger than the dose-effect relationship on recurrent cardiovascular events. Genetic variation and so-called Mendelian randomisation are experiments of nature that can give some insight into causality. In the context of variation over the IL-1 gene locus there have been a number of case association studies that indicate some, variable effect on cancer. A particular issue in this context is obtaining haplotypes that are both informative and exactly mirror the effect of the agent—in this case IL-1 beta inhibition. Unfortunately, the biggest such genetic study from the IL-1 genetics consortium (12) identifies a haplotype that more exactly mirrors anakinra (IL-1 receptor antagonist) and whilst this eliminates IL-1 beta signalling it also inhibits IL-1 alpha. In addition, genetic studies will impact on life-long risk, which may impact on tumour formation as well as presentation, the latter more likely to be affected by a short-term treatment of the type used in Cantos. Nonetheless this study, which incidentally reported IL-1 inhibitory haplotypes as increasing coronary risk (the opposite of the main Cantos study) in the supplementary data file shows effects of IL-1 inhibition on cancer cases. This study showed IL-1 inhibition to accentuate breast and renal cell cancer but there was a non-significant effect reducing lung cancer. It would seem that these genetic studies do not confirm or refute the lung cancer findings of Cantos but they might imply that there are specific cancer subtypes that are