Smoking a pack per day causes 150 mutations in every lung cell, research shows

LONDON – Scientists have found that smoking a pack a day of cigarettes can cause 150 damaging changes to a smoker's lung cells each year.

The findings come from a study of the devastating genetic damage, or mutations, caused by smoking in various organs in the body.

Publishing in the journal Science on Thursday, the researchers said the findings show a direct link between the number of cigarettes smoked in a lifetime and the number of mutations in the DNA of cancerous tumors.

The highest mutation rates were seen in lung cancers, but tumors in other parts of the body - including the bladder, liver and throat - also had smoking-associated mutations, they said. This explains why smoking also causes many other types of cancer beside lung cancer.

Smoking kills six million people a year worldwide and, if current trends continue, the World Health Organization predicts more than 1 billion tobacco-related deaths this century.

Cancer is caused by mutations in the DNA of a cell. Smoking has been linked with at least 17 types of cancer, but until now scientists were not clear on the mechanisms behind many of them.

Ludmil Alexandrov of Los Alamos National Laboratory in the United States, one of those who carried out the research, explained that in particular, it had until now been difficult to explain how smoking increases the risk of cancer in parts of the body that don't come into direct contact with smoke.

"Before now, we had a large body of epidemiological evidence linking smoking with cancer, but now we can actually observe and quantify the molecular changes in the DNA," he said.

This study analyzed over 5,000 tumors, comparing cancers from smokers with those from people who had never smoked.

It found certain molecular fingerprints of DNA damage - called mutational signatures - in the smokers' DNA, and the scientists counted how many of these were in different tumors.

In lung cells, they found that on average, smoking a pack of cigarettes a day led to 150 mutations in each cell every year. Each mutation is a potential start point for a "cascade of genetic damage" that can eventually lead to cancer, they said.

The results also showed that a smoking a pack of cigarettes a day led to an average 97 mutations in each cell in the larynx, 39 mutations for the pharynx, 23 for the mouth, 18 for the bladder, and six mutations in every cell of the liver each year.

Mike Stratton, who co-led the work at Britain's Wellcome Trust Sanger Institute, said it was a bit like digging in to the archaeology of each tumor

"The genome of every cancer provides a kind of archaeological record, written in the DNA code itself, of the exposures that caused the mutations," he said. "Looking in the DNA of cancers can provide provocative new clues to how (they) develop and thus, potentially, how they can be prevented."