Smoking affects the human genome – a complete set of DNA in a person, including all genes – in the form of DNA methylation, finds a new study published in an American Heart Association journal Circulation: Cardiovascular Genetics. Some DNA methylation sites have been found to persist even after 30 years of quitting.
DNA methylation is a process by which cells control gene activity, and it often modifies the function of genes. Scientists have found that DNA methylation could reveal a person’s smoking history, and as a result, they could develop targeted new therapies for diseases associated with smoking.
“These results are important because methylation, as one of the mechanisms of the regulation of gene expression, affects what genes are turned on, which has implications for the development of smoking-related diseases,” says Dr. Stephanie J. London, last author and deputy chief of the Epidemiology Branch at the National Institute of Environmental Health Sciences – part of the National Institutes of Health.
“Equally important is our finding that even after someone stops smoking, we still see the effects of smoking on their DNA,” she adds.
Cigarette smoking is a significant modifier of DNA methylation. Research has uncovered genes associated with smoking that contribute to the development of smoking-related diseases. DNA methylation is also a potential link between smoking and cancer, as well as prenatal cigarette smoke exposure and the development of chronic diseases in adults.
Despite smoking rates declining in many countries worldwide as a result of smoking campaigns and legislative action, even decades after people quit smoking, former smokers are at a long-term increased risk of diseases that include some cancers, chronic obstructive pulmonary disease, and stroke.
The molecular mechanisms behind these long-term effects are unclear. However, previous research has linked DNA methylation sites with genes connected to coronary heart disease and pulmonary disease, which suggests DNA methylation may play a role.
Researchers analyzed blood samples from almost 16,000 participants from 16 groups included in the Cohorts for Heart and Aging Research in Genetic Epidemiology (CHARGE) Consortium, including a group from the Framingham Heart Study that researchers have followed-up since 1971.
Compared with lifelong nonsmokers, the team found that DNA methylation sites associated with smoking were linked to more than 7,000 genes – accounting for one third of known human genes.
Findings suggest that the majority of DNA methylation sites in former smokers returned to levels observed in never smokers within 5 years of smoking cessation. However, some DNA methylation sites remained even 30 years after stopping smoking.
The most common DNA methylation sites detected were linked to genes associated with a greater risk of smoking-related diseases, such as cardiovascular diseases and certain cancers.
Investigators indicate that the long-term DNA methylation sites may emphasize genes that could put former smokers at risk of developing certain diseases years, even decades after quitting. This discovery could lead to researchers developing biomarkers to assess smoking history, which may result in new treatments emerging that could potentially target the methylation sites.
“Our study has found compelling evidence that smoking has a long-lasting impact on our molecular machinery, an impact that can last more than 30 years.”
Roby Joehanes, Ph.D., Harvard Medical School
“The encouraging news is that once you stop smoking, the majority of DNA methylation signals return to never smoker levels after 5 years, which means your body is trying to heal itself of the harmful impacts of tobacco smoking,” Joehanes concludes.