By Nermina Lamadema, Postdoctoral Research Associate at King's College London
According to numerous health monitoring organizations smoking in Bosnia and Herzegovina is an endemic problem with a potential to cause significant economic, social and health problems for the population of our country. Our country ranks amongst the highest consumers of tobacco per capita in the world with half of the adult population being active smokers and the numbers of young adolescent taking up smoking following continuous upward trajectory. This is in stark contrast we the generally observed trends globally where the tobacco taxes coupled with very strict legislation, have helped in reducing the numbers of active smokers. The effects of the smoking on the general health have been well established and studied in great detail. For example, it is well known that the cigarette smoke poses a major health hazard with a potential to cause serious damage to circulation, brain, lungs, heart, mouth and throat, stomach lining, skin, bones and reproductive health. Also very well elucidated are the effects of the so called passive or secondary smoke on the people that are in company of the active smokers and the effects on the unborn babies of pregnant smoking mothers.
For the purpose of this article we would like to focus our attention on so called ‘smoking footprint’ that is left on the human epigenome as a result of cigarette consumption. Epigenetics is a scientific field which deals with the effect of the environment on the gene activity which can have either beneficial or adverse effects on the cell health depending on the type of the environmental stimuli. Many environmental factors such as stress, alcohol, pollution and drugs, have a potential to negatively impact on the epigenetic signature of the cells primarily relating to the DNA and histone modifications which are mechanisms by which gene activity is regulated (for more details on these please consult previous issues of Ask magazine). Furthermore, these marks can potentially be impact or be transmitted to the offspring in a process known as transgenerational inheritance. The studies show smoking leaves distinct and long lasting effects on the human genome and even more specifically the epigenome with perhaps the largest footprint being left on the DNA methylation patterns. This particular environment responsive mark as previously discussed governs to a large extent the gene expression levels and can potentially silence specific genomic regions. The gain of the marks on the regulatory regions of the genes that govern for example cell proliferation status or other important cellular process is one of the hallmarks of cancer and many other diseases.
Smoking and Epigenetics
Researchers have followed the epigenetics signatures of DNA methylation for a long time now typically using very large cohort of smokers to assess the genome wide effects. These studies are subjected to so-called meta-analysis of DNA methylation patterns to assess what effects (if any) smoking had on this important epigenetic mark. One such study was being performed by Research in Genetic Epidemiology (CHARGE) Consortium of the Cohorts for Heart and Aging, on blood samples from 16,000 participants from 16 groups and they studied changes to the DNA methylation genome wide between smokers, former smokers and people that never smoked. The most significant finding was that about third or 7000 genes became marked by distinct DNA methylation marks and also for people that stopped smoking (within five years of quitting smoking), most of these sites returned to the levels seen in people that never smoked. However, it appears that some of the sites persisted even after 30 years of quitting smoking, the most significant genomic regions that become marked by the changes in DNA methylations are linked to the genes that are associated with diseases such as some cancers and cardiovascular diseases. Another recent study worth a mention was looking to determine what are the epigenetic changes in the cheek cells of smoker compared to non-smokers. Studying these cells which are relatively easy to collect by doing a cheek swab can provide really good assessments of the smoking effects because the cells are in direct contact with the cigarettes and have been linked to epithelial cancers (such as lung) incidences. Indeed, what they observed were significant changes in DNA methylation patterns of the cheek cells of the smokers with around 40-fold increase in aberrant DNA methylation sites which scientists call differential methylation sites (DMR) in comparison to the corresponding blood samples of the non-smokers. Therefore, smoking negatively impact on the cell epigenome by seeding the aberrant methylation marks on the genome which impacts on the cells ability to properly form and differentiate – which is cell’s ability to transition from cell type to another in order to become more specialized. This is a common hallmark of cancer cells which becomes trapped in its undeveloped, non-differentiated state. Studies on the human bronchial cells, which were exposed for 15 months, to the liquid form of cigarette smoke comparable to smoking one to two packs of cigarettes daily found a significant change to the DNA methylation epigenetics status of the cells but also increase in the enzymes that can regulate the epigenetic modifications. Researchers at Johns Hopkins Kimmel Cancer Centre go on to conclude that based on their results it appears that early epigenetic changes triggered by chronic cigarette smoke exposure can build up over time and make the airway cells increasingly sensitive to responding to mutations that initiate cancer such is for example KRAS, which is a frequently mutated gene, found present in one-third of lung cancers which are smoking-related. They go on further to add that smokers by quitting altogether can lower their risk of cancer, and the sooner a smoker quits, the lower their lung cancer risk may be.
Smoking and Pregnancy – Epigenetics
Maternal cigarette smoking during pregnancy can be considered as one of the most harmful environmental exposures that can influence growth and development of the foetus as well having an effect on maternal health raising a possibility of complications. The likelihood of still birth and miscarriages is increased probably due to the exposure to numerous dangerous chemicals, such as nicotine, carbon monoxide, and tar which are contained in the cigarettes and which easily cross the placenta. In the next edition of Ashq we will focus a bit more on the effects of smoking as well as passive smoking on the health with a specific emphasis on the epigenetics footprints left by such exposures.
Ref. Roby Joehanes, et al Epigenetic Signatures of Cigarette Smoking. Circulation: Cardiovascular Genetics, 2016; CIRCGENETICS.116.001506
Andrew E. Teschendorff, et al Correlation of smoking – associated DNA methylation changes in Buccal Cells with DNA methylation changes in epithelial cancer, JAMA Oncology, 2015.
Knopik et al The Epigenetics of Maternal Cigarette Smoking during Pregnancy and Effects on Child Development, Dev Psychopathol, 2013
Članak „Pušenje i epigenetika“ na bosanskom jeziku možete pročitati u 20. broju magazina AŠK, mart 2018.