NIH study suggests smoking may leave a 'legacy effect' even after stopping

DNA methylation is a well-studied chemical modification to DNA, altering the way genes are expressed, and active DNA methylation has been linked to healthy development as well as disease progression. Now National Institutes of Health (NIH) researchers say DNA methylation is persistently altered in individuals with a smoking history, and the results may lead to new therapy targeting pathways involved in disease. 

Stephanie London and her team from the National Institute of Environmental Health Sciences published the results in the journal Circulation: Cardiovascular Genetics.

The genome is the collection of DNA found in the majority of cells in living organisms. How the genome is organized and chemically modified dictates how it's decoded into proteins and other molecules necessary for the survival of a cell and the organism as a whole. DNA methylation, a chemical modification also referred to as an “epigenetic” modification to the genome, was thought to be relevant only during development.

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In a large meta-analysis that included 16,000 patients from the CHARGE consortium, the researchers show that these DNA methylation “marks” are established during the smoker’s life and remain there even after the individual gives up smoking, laying down a legacy effect.

"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 London in a release. "Equally important is our finding that even after someone stops smoking, we still see the effects of smoking on their DNA."

Some of their major findings include:

  • 7,000 genes were found to have smoking-associated DNA methylation marks
  • The majority of these marks were reversed to normal after 5 years of quitting smoking
  • Some of these marks persisted even 30 years after quitting smoking
  • Statistically significant marks were associated with cardiovascular diseases and certain cancers.

The findings could be important to establish whether having a smoking background leaves molecular signatures that might increase the susceptibility to disease, even decades after individuals stop smoking.

The researchers say the main analysis wasn’t the longitudinal study but rather the association with epigenetic marks at the time of the individual smoking. Nevertheless, epigenetics regulation driving “molecular memory” has been proposed by a number of research groups now and this study is a landmark in smoking associated epigenetic changes. 

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