Investigators may have uncovered differential associations between smoking and DNA methylation across various racial and ethnic groups, according to a recent study published by Huang et al in the American Journal of Human Genetics. The findings could lead to the development of new strategies to predict the risk of lung cancer.
Background
Smoking often changes how genes are expressed, which can contribute to the development of lung cancer and other smoking-related diseases. For instance, Black individuals who smoke may face a higher risk of lung cancer compared with non-Hispanic White individuals who smoke, whereas Hispanic individuals may face a lower risk compared with non-Hispanic White individuals. However, the link between epigenetics and smoking is not fully understood, especially as it applies to differences across racial and ethnic groups. Prior research on smoking and epigenetics has focused on just one or two racial groups at once.
“We know that smoking affects [individuals] differently based on their race and ethnicity, but identifying epigenetic signatures of smoking would help us better predict risk for smoking-related diseases,” explained lead study author Brian Huang, PhD, Assistant Professor in the Department of Population and Public Health Sciences at the Keck School of Medicine at the University of Southern California.
Study Methods and Results
In the recent study, the investigators used data from the Multiethnic Cohort Study to analyze the outcomes of 1,994 individuals who identified as Black (n = 364), White (n = 397), Japanese (n = 522), Latino (n = 400), and Native Hawaiian (n = 311). Utilizing the biological samples from the participants, they then quantified smoking by calculating each of their total nicotine equivalents as well as their levels of DNA methylation across the genome at markers known as cytosine-phosphate-guanine (CpG) sites. This enabled them to achieve more accurate calculations of the participants’ smoking doses compared with the calculations acquired through self-reported measures.
The investigators discovered that smoking was linked to DNA methylation at 408 CpG sites, including 45 new sites that were not previously identified and two sites that carried a significant risk difference depending on race or ethnicity. One of the sites on the CYTH1 gene only showed changes in Black individuals who currently smoked, whereas a second site on the MYO1G gene was most strongly linked with epigenetic changes in Latino individuals who currently smoked. Those genes performed functions that related to cancer progression and other disease processes.
“This gives us an indication that [total nicotine equivalents] can provide more information beyond what we already know from self-reported measures of smoking,” Dr. Huang emphasized.
To further confirm their findings, the investigators collected total nicotine equivalents and DNA methylation data from 340 participants from the Singapore Chinese Health Study and 394 participants from the Southern Community Cohort Study. They identified many of the same CpG sites found in the Multiethnic Cohort Study, including the sites most strongly associated with total nicotine equivalents—providing additional evidence that the strongest epigenetic markers of smoking may be consistent across multiple racial and ethnic groups.
Conclusions
“This study gives us some additional information about the mechanism by which smoking can affect health, and how that could differ across various populations. Ultimately, that can lead to better prediction, early detection, and treatment for smoking-related [diseases],” Dr. Huang highlighted.
The recent findings could improve the understanding of why some populations face a higher risk of lung cancer than others.
“By conducting these joint studies, we can understand the mechanism by which DNA methylation acts as a mediator between smoking and lung cancer, which can in turn improve our ability to predict lung cancer risk,” Dr. Huang underscored.
Currently, Dr. Huang and his colleagues are exploring epigenetic changes associated with additional biomarkers of smoking, including biological levels of cadmium, a heavy metal found in cigarette smoke. The investigators hope to conduct further epigenome-wide association studies of DNA methylation to better understand how epigenetic changes can increase an individual’s risk of developing lung cancer.
Disclosure: The research in this study was supported by the National Institutes of Health and the National Cancer Institute. For full disclosures of the study authors, visit sciencedirect.com.
