Smoking stays in your genes after you quit

Heidi Ledford

Gene expression changes brought on by heavy smoking may persist long after the smoker has kicked the habit, researchers have found. The results could provide a molecular explanation for the continued increased risk of lung cancer and other pulmonary ailments among former smokers.

When smokers quit, their bodies gradually begin to undo the damage cigarettes have wrought. But contrary to popular belief, not all of the body's systems make a full recovery. Although the risk of heart disease, for example, eventually returns to that of a nonsmoker, the risk of getting lung cancer and emphysema - a progressive lung condition that leaves sufferers struggling for breath - remains elevated even if the patient hasn't smoked a cigarette in decades.

"You are reducing the risk of disease by quitting," says Raj Chari, a cancer biologist at the British Columbia Cancer Research Centre in Vancouver, Canada, "but it isn't going back to zero."

Chari and his co-workers assayed gene expression levels in tissue scraped from the airways of four nonsmokers (who had never smoked), eight current smokers, and twelve former smokers who had gone without a cigarette for at least 1 year, and up to 32 years.

They found that some genes with altered expression in smokers had returned to normal levels in former smokers. But the expression of another 124 genes had not returned to normal. The results are published today in BMC Genomics¹.

Breathe uneasy

The proteins produced by several of these genes are associated with lung diseases. For example, several genes related to the cell cycle were expressed at lower levels in both former and current smokers. This is consistent with the reduced rates of cell division in the airways of patients with chronic bronchitis or emphysema.

Similarly, several genes that encode proteins involved in DNA repair were also expressed at lower levels in former and current smokers.

Illness could be another explanation for the altered gene expression. The former smokers in the study were all heavy users who smoked at least a pack of cigarettes a day for 30 years or more, and all of them also showed signs of chronic bronchitis or emphysema. But Chari and his co-workers found that the gene expression patterns did not correlate with the severity of lung disease, which suggests that something else was to blame.


Another, as yet unpublished, study by Avrum Spira, a pulmonary specialist at Boston University, Massachusetts, supports the notion that smoking itself induces the long-lasting genetic changes. Spira says he has also found gene expression differences in a study using healthy former smokers.

"Cells in the airway appear to have changes at a molecular level that persist many years after quitting," says Spira, commenting on Chari's work. Such studies are important starting points, Spira says, but do not themselves establish a cause-and-effect relationship between altered gene expression and lung disease. To better address this question, Spira is preparing to launch a study that will track gene expression changes and disease rates in individual smokers before and after they kick the habit.

Reference : Chari , R., et al. BMC Genomics 8 , 297 (2007).