DNA damage caused by smoking may last a lifetime

By Kate Bass, B.Sc.Sep 23 2016

Results of a study published this week show that the effects of smoking on DNA are wide-reaching and some persist long after a person has stopped smoking. The information gained may help improve our understanding of smoking-related diseases.

The harmful effects of smoking reach almost every organ of the body and dramatically increase the risk of developing respiratory disease, cardiovascular disease and cancer, most notable of the lungs and throat. Consequently, it can dramatically reduce both a person's quality of life and their life expectancy.

There has been a considerable decline in the number of people smoking in recent years after hard-hitting campaigns emphasizing the health risks associated with smoking, and increased taxation on tobacco.

Nonetheless, smoking remains a global epidemic that kills around 6 million people each year. It is a leading cause of preventable death and disease.

Although it is well known that smoking has a long-term detrimental impact on health, the mechanisms through which this occurs have not been fully elucidated. Earlier studies had shown that methylation of DNA affects genes linked with coronary heart disease and pulmonary disease.

DNA methylation can modify the function of a gene, determining whether or not the encoded protein is produced, and is an important mechanism by which the body regulates gene expression. Consequently, researchers have now examined the effects of smoking on DNA methylation.

Researchers measured the levels of DNA methylation in blood samples taken from nearly 16,000 volunteers, including a group of participants in the Framingham Heart Study that has been followed by researchers since 1971.

DNA methylation sites across the human genome were compared between current smokers, former smokers and those who have never smoked.

The results showed that smoking resulted in DNA methylation of more than 7,000 genes, which is around a third of known human genes. The methylation levels of 1,405 genes were statistically significantly different among smokers compared with people who had never smoked.

These genes were strongly associated with diseases caused by cigarette smoking, such as cardiovascular diseases and certain cancers.

It was found that within five years of a person stopping smoking, the level of DNA methylation at most sites had returned to those seen in people who have never smoked.

However, researchers identified some sites of smoking-associated DNA methylation that persisted even 30 years after a person had stopped smoking. Former smokers are thus still at increased risk of developing certain diseases.

The pattern of DNA methylation could therefore provide a footprint reflecting an individual’s smoking history. These findings could enable the development of new therapies targeting affected 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...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."

Roby Joehanes, an instructor at Harvard Medical School.