Attention smokers: For every year that you continue your pack-a-day habit, the DNA in every cell in your lungs acquires about 150 new mutations.

Some of those mutations may be harmless, but the more there are, the greater the risk that one or more of them will wind up causing cancer.

The threat doesn’t stop there, according to a study in Friday’s edition of the journal Science. After a year of smoking a pack of cigarettes each day, the cells in the larynx pick up roughly 97 new mutations, those in the pharynx accumulate 39 new mutations, and cells in the oral cavity gain 23 new mutations.

Even organs with no direct exposure to tobacco smoke appear to be affected. The researchers counted about 18 new mutations in every bladder cell and six new mutations in every liver cell for each “pack-year” that smokers smoked.


The findings are based on a genetic analysis of 5,243 cancers, including 2,490 from smokers and 1,063 from patients who said they had never smoked tobacco cigarettes.

At this point, it should come as no surprise that cigarettes are bad for your health. The U.S. surgeon general has warned about the dangers of smoking for more than 50 years. The American Cancer Society recently calculated that in a single year, at least 167,133 cancer deaths in the U.S. could be blamed on smoking.

But the new study offers a clearer picture of how smoking does its deadly damage.

The researchers used powerful supercomputers to compare thousands of cancer genome sequences. The computers grouped the sequences into about 20 distinct categories, or “mutational signatures.” Mutations tied to five of these signatures were more common in tumors from smokers than in tumors from nonsmokers.


One of the signatures involves a specific DNA nucleobase change — instead of a C for cytosine, there was an A for adenine — that “is very similar” to the change that occurs in the lab when cells are exposed to benzo[a]pyrene, a compound that the International Agency for Research on Cancer says is carcinogenic to humans.

Most of the lung and larynx cancers obtained from smokers had this type of mutation, the researchers reported. They also found that the signature was more common among smokers than nonsmokers.

Another mutational signature was characterized by Cs that should have been Ts (thymine) and vice versa. Although these changes can be found in all kinds of cancers, the signature was 1.3 to 5.1 times more common in tumors from smokers than in tumors from nonsmokers, according to the study.

The researchers said they think these kinds of mutations have the effect of speeding up the “clock” inside of cells. The faster a cellular clock runs, the more chances the cell’s DNA has to mutate.


“The way tobacco smoking causes cancer is more complex than we thought,” study coauthor Mike Stratton, director of the Wellcome Trust Sanger Institute in England, said in a statement.

karen.kaplan@latimes.com

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