Each extra cigarette generates more molecular damage Mito Images/REX/Shutterstock

The numbers are in. We can now precisely count how many cancer-related DNA mutations accumulate in smokers’ organs over time.

On average, there is one DNA mutation per lung cell for every 50 cigarettes smoked, according to a new analysis. People who smoke a pack of 20 a day for a year generate 150 mutations per lung cell, 97 per larynx cell, 39 per pharynx cell, 18 per bladder cell and six per liver cell.

Epidemiological studies previously linked tobacco smoking with at least 17 classes of cancer, but this is the first time researchers have been able to quantify the molecular damage inflicted on DNA.


Ludmil Alexandrov at Los Alamos National Laboratory in New Mexico and his colleagues achieved this by comparing tumour DNA from 2500 smokers and 1000 non-smokers. This allowed them to identify which mutations were associated with smoking.

Theoretically, every DNA mutation has the potential to trigger a cascade of genetic damage that causes cells to become cancerous. However, we still don’t know what the probability is of a single smoking-related DNA mutation turning into cancer, or which mutation types are likely to be more malignant. “This is research we are currently pursuing,” Alexandrov says.

Russian roulette

Some smokers never develop cancer despite accruing thousands of mutations, but this is purely down to luck, Alexandrov says. “Smoking is like playing Russian roulette: the more you play, the higher the chance the mutations will hit the right genes and you will develop cancer,” he says. “However, there will always be people who smoke a lot but the mutations do not hit the right genes.”

The team hopes their findings will deter people from taking up smoking and debunk the myth that social smoking is harmless. Every cigarette has the potential to cause genetic mutations, Alexandrov says.

Quitting smoking will not reverse these mutations – they leave permanent scars on DNA – but it will prevent the added risk of more mutations, he says.

There is good evidence that people who stop smoking have a significantly lower risk of premature death than those who continue, says Simon Chapman at the University of Sydney, Australia.

For example, a UK study that followed 35,000 men for half a century found that smoking shaved 10 years off average life expectancy. But quitting at age 30 mostly erased the risk of premature death, and giving up at 50 halved it.

“Many smokers believe there’s no point in quitting because the damage is already done,” says Chapman. “But if smokers quit by middle age, they can avoid nearly all the excess risk of tobacco-caused deaths.”

Journal reference: Science, DOI: 10.1126/science.aag0299