Smoking tobacco leaves the chemical footprints on DNA. Tobacco smoke leaves its mark on DNA by changing a chemical code on the DNA molecule that can sometimes change gene activity, according to a new study.
Some of these molecular changes revert to their original state when a smoker quits, but others persist in the long term, the researchers found.
Experts have known for some time that smoking causes changes of the DNA molecule, but they are now learning more about how widespread the changes are, and what they may mean, said senior author Dr. Stephanie J. London, chief of the Epidemiology Branch at the National Institute of Environmental Health Sciences in Research Triangle Park, North Carolina.
“We don’t really know whether it means ‘damage’ to the DNA,” London told Reuters Health. “That requires more study, using data outside what we have here. What we’re saying is that it’s a change to your DNA that can have a downstream effect on what genes are expressed at what levels.”
The researchers combined data from 16 sets of participants in a previous study of aging, totaling more than 15,000 people who had provided blood samples that were analyzed for a type of DNA change known as methylation.
The DNA molecule contains instructions for growth and development in the form of genes, and so-called methyl groups along the molecule’s surface – collections of hydrogen and carbon atoms – can determine which genes get activated.
The study team compared 2,433 current smokers – those who said they smoked at least once a day sometime over the last year – to 6,518 former smokers who had stopped at least one year before the blood draw and 6,596 never smokers.
Current smokers had 2,623 different methylated locations on their genes compared to never smokers.
That corresponds to 7,000 potentially affected genes, many of which are implicated in various cancers, high blood pressure and other health outcomes of smoking, said lead study author Roby Joehanes of Beth Israel Deaconess Medical Center and Harvard Medical School in Boston. But future studies will need to complete the chain from DNA changes to gene expression to disease outcome, he said.
Only 185 of the methylated locations were still significantly different between former smokers and never smokers, according to the results reported in Circulation: Cardiovascular Genetics. “Many people think that after five years your health is mostly back to that of a nonsmoker, but that may not be the case,” Joehanes told Reuters Health.
“Stop smoking now because many, many, many of the effects of smoking will go away,” London said. Since so many genes were involved, the researchers didn’t look at individual changes and their possible health effects, she noted.
In future studies of other environmental influences on health, using methylated DNA as a marker of former smoking may help rule out tobacco as a confounding cause, she said. There is already an effective test to detect recent smoking, but not one for smoking that happened decades ago.
The unhealthy habit leaves its lifelong mark in the form of ‘DNA methylation’, a process by which cells control gene activity. The findings, published in Circulation: Cardiovascular Genetics, suggest it could reveal an individual’s smoking history, offering hope of developing better therapies.
Dr Stephanie London, of the National Institute of Environmental Health Sciences in the US, said: “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.
“Equally important is our finding even after someone stops smoking, we still see the effects of smoking on their DNA”. Smoking remains the leading preventable cause of death worldwide, despite a decline in many countries as a result of campaigns and legislative action. Even decades after stopping, former smokers are at long term risk of developing cancers, chronic obstructive pulmonary disease and stroke.
The molecular mechanisms remain poorly understood, but previous studies linking DNA methylation sites to genes involved with coronary heart disease and pulmonary disease suggest it may play an important role. Dr London and colleagues pooled data from 16 previous studies which analysed blood samples from a total of 16,000 people. They found smoking associated DNA methylation sites were associated with more than 7,000 genes, about a third of all known human genes. For people who gave up, most returned returned to levels seen in never smokers within five years.But some persisted even after 30 years of remaining nicotine free.
The most statistically significant were linked to genes associated with numerous illnesses caused by smoking, including heart disease and certain cancers. Their discovery raises the possibility of developing biomarkers to evaluate a patient’s smoking history, as well as potentially developing new treatments targeted toward these methylation sites. Lead author Dr Roby Joehanes, of Harvard Medical School in the US, said: “Our study has found compelling evidence smoking has a long lasting impact on our molecular machinery, an impact that can last more than 30 years.