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November 7, 2016

Smoking causes 'hundreds' of genetic mutations per year, study finds

Daily Briefing

A pack-a-day habit causes hundreds of mutations in each cell of smokers' lungs and other organs per year, which increases their likelihood of developing cancer, according to a study published Friday in the journal Science.

It's widely known that smoking is bad for your health. Smoking kills six million people globally per year, according to the World Health Organization, and is expected to kill more than one billion people this century if current trends continue. "But the new study offers a clearer picture of how smoking does its deadly damage," Karen Kaplan writes for the Los Angeles Times' "Science Now."

BBC News reports the analysis shows a direct link between the number of cigarettes smoked and the number of mutations in the DNA of smokers' cells.

Study details

For the study, researchers genetically analyzed about 5,200 cancer genome sequences of cancer classes for which smoking heightens risk—including about 2,500  genome sequences from smokers and about 1,000 cancers from patients who reported never having smoked tobacco.

The researchers identified about 20 "mutational signatures" in the genome sequences, five of which appeared more in genome sequences from smokers than nonsmokers.

The researchers found that smoking led to more mutations in each cell, which led to more opportunities for cancer to develop.

The researchers estimated that after smoking a pack of cigarettes—defined as 20 cigarettes—daily for one year:

  • Every lung cell gains 150 mutations;
  • Every larynx cell gains 97 mutations;
  • Every pharynx cell gains 39 mutations;
  • Every oral cavity cell gains 23 mutations;
  • Every bladder cell gains 18 mutations; and
  • Every liver cell gains six mutations.

According to the study, some of the mutational signatures in smokers were similar to mutations that occur when cells are exposed to benzoapyrene, a carcinogenic substance. Most of the cancers found in smokers' lungs and larynx had this type of mutation.

The researchers said the mutations likely increase how quickly the cells' internal clock runs, which gives the cells' DNA more chances to change. Study co-lead author Mike Stratton said, "The more mutations there are, the higher the chance that these will occur in the key genes that we call cancer genes, which convert a normal cell into a cancer cell."

But the exact reason why smoking accelerates the mutational process is "mysterious and complex," Stratton said.

The study "offers fresh insights into how tobacco smoke causes cancer," said co-lead author Ludmil Alexandrov. "Tobacco smoking damages DNA in organs directly exposed to smoke as well as speeds up a mutational cellular clock in organs that are both directly and indirectly exposed to smoke."

According to the researchers, the changes do not reverse if a person quits smoking (Kaplan, "Science Now," Los Angeles Times, 11/3; Walsh, BBC News, 11/3; Kelland, Reuters, 11/3; DOE/Los Alamos National Laboratory release, 11/4; Alexandrov et al., Science, 11/4).

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