Etude suédoise sur les dangers de la cigarette

Exposure to environmental and lifestyle factors, such as cigarette smoking affect the epigenome and might mediate risk for diseases and cancers. We have performed a genome-wide DNA methylation study to determine the effect of smoke and snuff (smokeless tobacco) on DNA methylation. A total of 95 sites were differentially methylated (FDR q-values<0.05) in smokers and a subset of the differentially methylated loci were also differentially expressed in smokers. We found no sites, neither any biological functions or molecular processes enriched for smoke-less tobacco related differential DNA methylation This suggests that methylation changes are not caused by the basic components of the tobacco but from its burnt products. Instead we see a clear enrichment (FDR q-value<0.05) for genes, including CPOX, CDKN1A, and PTK2, involved in response to arsenic-containing substance, which agrees with smoke containing small amounts of arsenic. A large number of biological functions and molecular processes with links to disease conditions are also enriched (FDR q-value<0.05) for smoke related DNA methylation changes. These include “insulin receptor binding”, and “negative regulation of glucose import” which are associated with diabetes, “positive regulation of interleukin-6-mediated signaling pathway”, “regulation of T-helper 2 cell differentiation”, and “positive regulation of interleukin-13 production” which are associated with the immune system, and “sertoli cell fate commitment” which is important for male fertility. Since type 2 diabetes, repressed immune system and infertility have previously been associated with smoking; our results suggest that this might be mediated by DNA methylation changes.

We found no sites, neither any biological functions or molecular processes enriched for smoke-less tobacco related differential DNA methylation This suggests that methylation changes are not caused by the basic components of the tobacco but from its burnt products.

This work was supported by the Swedish Medical Research Council (2011-2354), the Swedish Society for Medical Research (SSMF), and Göran Gustafssons Stiftelse.