Cigarette Smoking and Epigenetics: DNA Methylation Differences Between Ethnic Groups
Cigarette smoking leads to some of the most preventable causes of death and illness in the world. The Centers for Disease Control (CDC) in the United States has reported that there are approximately 440,000 deaths due to smoking each year, and an additional 49,000 deaths due to secondhand smoke. Roughly 600 chemicals are found in a cigarette, and after burning approximately 4,000 chemicals are generated, so it is not surprising that smoking can lead to various diseases, such as emphysema, cancer, and heart-related diseases. Past studies have shown correlations between smoking and changes in DNA methylation levels at certain genes, but the effect of smoking on DNA methylation is different between ethnic groups due to genetic and behavioral differences between populations. Learning more about the susceptibility of different ethnic groups to smoking-related diseases is of great importance due to the recent increases in tobacco use in certain parts of the world, such as South Asian countries, because the increased smoking rates will lead to future population health issues.
The effect of cigarette smoking on certain ethnic groups was recently studied by Elliot et al. from the University of Bristol in the United Kingdom. The authors looked to further understand DNA methylation patterns between two distinct ethnic groups, South Asians and Europeans, to explore if smoking behaviors can be determined by epigenetic profiling, and they also developed an epigenetic scoring method to characterize smoking behavior. Through a population-based cohort from Southall And Brent REvisited (SABRE), 192 men between the ages of 40-55 were studied based on ethnicity and smoking status (current smokers, former smokers, or non-smokers), and genome-wide DNA methylation patterns from blood samples were investigated.
The authors used a very stringent statistical threshold to identify differential DNA methylation patterns in current smokers and discovered 29 individual CpGs at 18 unique loci that exhibited a greater than 5% difference in DNA methylation levels. The most striking difference was at the AHRR locus (which is associated with lung cancer), which showed a 22% DNA methylation difference in smokers relative to non-smokers. For European smokers, the DNA methylation level of the AHRR locus was noticeably lower than South Asians smokers. Furthermore, ethnic differences in DNA methylation were also found in non-smokers at two loci, 6p21.33 and GNG12, which could be due to other environmental factors (such as diet) or a specific ethnic factor that is independent of smoking status. DNA methylation data were further analyzed using the Random Forests calculation, which was used to create a threshold score to predict the smoking status of individuals in each ethnic group. In both ethnic groups, former smokers and non-smokers showed similar low scores, supporting past evidence that former smokers slowly regress back to non-smoker methylation levels over a long period of time. For Europeans, current smokers are more differentially seen above the threshold than South Asians. The model correctly predicted current smokers from former smokers and non-smokers with 100% sensitivity and 97% specificity for Europeans and 80% sensitivity and 95% specificity for South Asians.
In summary, Elliot et al. performed epigenetic analysis of different ethnic groups in relation to their smoking exposure levels, and found that ethnic differences in DNA methylation may provide more insight into molecular pathways that could account for smoking-related diseases in certain populations. Additionally, they developed an improved epigenetic smoking score that will help provide more information on the smoker status of individuals based on DNA methylation profiles, which will allow for a true association between smoking and smoking-related diseases.
Elliott HR, Tillin T, McArdle WL, Ho K, Duggirala A, Frayling TM, Davey Smith G, Hughes AD, Chaturvedi N, & Relton CL (2014). Differences in smoking associated DNA methylation patterns in South Asians and Europeans. Clinical epigenetics, 6 (1) PMID: 24485148