Smoking leaves its “footprint” in your DNA, according to research released Tuesday.

The new findings suggest that DNA methylation — a process by which cells control gene activity — could reveal a person’s smoking history and provide researchers with potential targets for new therapies.

“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,” said the study’s senior author Stephanie J. London, M.D., Dr.P.H., deputy chief of the Epidemiology Branch at the National Institutes of Health’s National Institute of Environmental Health Sciences. “Equally important is our finding that even after someone stops smoking, we still see the effects of smoking on their DNA.”

Smoking is the leading preventable cause of death worldwide, despite a decline in smoking in many countries as a result of smoking cessation campaigns and legislative action.

Even decades after stopping, former smokers are at long-term risk of developing diseases including some cancers, chronic obstructive pulmonary disease and stroke. The molecular mechanisms responsible for these long-term effects 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.

Researchers conducted a meta-analysis of DNA methylation sites across the human genome using blood samples from nearly 16,000 participants. Comparing DNA methylation sites in current and former smokers to those who never smoked, they found:

  • Smoking-related DNA methylation sites were associated with more than 7,000 genes, or one-third of known human genes.
  • For people who stopped smoking, the majority of DNA methylation sites returned to levels seen in never-smokers within five years of quitting smoking.
  • Some DNA methylation sites persisted even after 30 years of quitting.
  • The most statistically significant methylation sites were linked to genes enriched for association with numerous diseases caused by cigarette smoking, such as cardiovascular diseases and certain cancers.

“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,” said study lead author Roby Joehanes, Ph.D., an instructor at Harvard Medical School in Boston. “The encouraging news is that once you stop smoking, the majority of DNA methylation signals return to never-smoker levels after five years, which means your body is trying to heal itself of the harmful impacts of tobacco smoking.”

The study is published in the American Heart Association journal Circulation: Cardiovascular Genetics.