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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.

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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</s>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.

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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.

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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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Mexico’s soda tax will save 18,900 lives and more than $983 million over 10 years, study says</s>(CNN) The vast amount of damage that smoking can have on your DNA has been revealed in a new study exploring how tobacco smoke affects cells within the human body.

Consuming a pack of cigarettes every day for a year can cause multiple changes in cells within various parts of the body, according to the study, published in the journal Science on Thursday.

The cells in parts of the body that are directly exposed to smoke are particularly damaged, with 150 mutations found to occur in lung cells within one year, 97 in the larynx and 39 in the oral cavity.

"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." said Ludmil Alexandrov of the Los Alamos National Laboratory in Los Alamos, New Mexico, who led the study.

In other words, it accelerates the occurrence of genetic mutations, increasing the risk of cancer.

"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 due to cigarette smoking," Alexandrov said.

Tobacco smoke is a mixture of chemicals, of which 60 are known to be carcinogens thought to cause cancer by aiding the occurrence of mutations within genes. With an increased number of mutations, there's a greater chance that they will happen within known cancer-causing genes.

"With this study, we have found that people who smoke a pack a day develop an average of 150 extra mutations in their lungs every year, which explains why smokers have such a higher risk of developing lung cancer," Alexandrov said.

According to the American Lung Association, men who smoke are 23 times more likely to develop lung cancer than someone who's never smoked, and women are 13 times more likely.

The researchers scanned the genome sequences of more than 5,000 tumors from 17 types of cancer for which smoking is a risk factor. These were obtained from smokers and nonsmokers alike for comparison.

In addition to the mutations, the analysis found a range of "molecular signatures" -- patterns that are significantly different from other sequences in the DNA -- based on changes to DNA that were linked to people smoking.

One signature was found in tissues directly exposed to smoke, and an unrecognized signature was more widely found in all smoking-related cancers. That mysterious signature appeared to increase the rate of premature mutations and appeared to correlate with age, with the total number of mutations linking to the age when someone was diagnosed.

"Mutations caused by direct DNA damage from carcinogens in tobacco were seen mainly in organs that come into direct contact with inhaled smoke," he added. "In contrast, other cells of the body suffered only indirect damage, as tobacco smoking seems to affect key mechanisms in these cells that in turn mutate DNA."

The researchers also looked at any changes in DNA methylation -- the process in which a molecule known as a methyl group sits on the surface of DNA to influence gene activity -- and saw limited differences between smokers and nonsmokers.

"I think one of the interesting things in this paper is the lack of methylation changes in tumor DNA related to smoking, when we do see significant changes in normal DNA between smokers and nonsmokers," said Dr. James Flanagan, a cancer geneticist at Imperial College London who was not involved in the study.

Flanagan's recent research has found that tobacco leaves a legacy on a smoker's DNA through methylation to influence whether genes are active or silent. He believes it's presumptive to say there's no role for methylation in these changes.

"I would assume that means the methylation is just so much more variable in tumors that the smoking-associated markers get lost in the statistical analysis. You can't argue from this that methylation changes from smoking are not important for cancer development."

But these new findings still shed valuable light on the way tobacco smoke increases the risk of cancer, particularly in parts of the body that are not actually exposed to smoke.

"The genome of every cancer provides a kind of 'archaeological record,' written in the DNA code itself, of the exposures that caused the mutations that lead to the cancer," said Sir Mike Stratton, director of the Wellcome Trust Sanger Institute in the UK, who co-led the research, in a statement. "Our research indicates that the way tobacco smoking causes cancer is more complex than we thought."

Stratton added, "this study of smoking tells us that looking in the DNA of cancers can provide provocative new clues to how cancers develop and thus, potentially, how they can be prevented."</s>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."</s>WASHINGTON -- Smoking a pack of cigarettes a day causes an average of 150 mutations a year in lung cells, according to a new study that identifies specific ways smoke exposure damages DNA.

The research, published Thursday in the journal Science, analyzes and compares tumors, providing the first accurate measure of the devastating genetic damage smoking inflicts not only in lungs but also in other organs not directly exposed to smoke.

Although it was previously known that smoking contributes to at least 17 types of human cancers, it had remained unclear exactly how cigarettes caused tumors, according to the researchers from Britain's Wellcome Trust Sanger Institute and the Los Alamos National Laboratory in the United States.

Although they saw the largest number of genetic mutations in lung tissue, other parts of the body also displayed changes in DNA, helping explain how smoking causes various types of cancer.

Cigarettes contain more than 7,000 different chemicals, of which 70 are known to be carcinogenic, the researchers said, pointing to the complexity of how smoke interacts with the body.

"This study offers fresh insights into how tobacco smoke causes cancer," said Ludmil Alexandrov of the Los Alamos National Laboratory, one of the study's main co-authors.

"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 due to cigarette smoking," he added.

"With this study, we have found that people who smoke a pack a day develop an average of 150 extra mutations in their lungs every year, which explains why smokers have such a higher risk of developing lung cancer."</s>In this June 22, 2012, file photo, a smoker snuffs out a cigarette at the Capitol in Sacramento, California (AP photo)

WASHINGTON — Smoking a pack of cigarettes a day causes an average of 150 mutations a year in lung cells, according to a new study that identifies specific ways smoke exposure damages DNA.

The research, published on Thursday in the journal Science, analyses and compares tumours, providing the first accurate measure of the devastating genetic damage smoking inflicts not only in lungs but also in other organs not directly exposed to smoke.

Although it was previously known that smoking contributes to at least 17 types of human cancers, it had remained unclear exactly how cigarettes caused tumours, according to the researchers from Britain's Wellcome Trust Sanger Institute and the Los Alamos National Laboratory in the United States.

Although they saw the largest number of genetic mutations in lung tissue, other parts of the body also displayed changes in DNA, helping explain how smoking causes various types of cancer.

Cigarettes contain more than 7,000 different chemicals, of which 70 are known to be carcinogenic, the researchers said, pointing to the complexity of how smoke interacts with the body.

"This study offers fresh insights into how tobacco smoke causes cancer," said Ludmil Alexandrov of the Los Alamos National Laboratory, one of the study's main co-authors.

"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 due to cigarette smoking," he added.

"With this study, we have found that people who smoke a pack a day develop an average of 150 extra mutations in their lungs every year, which explains why smokers have such a higher risk of developing lung cancer."

In the first comprehensive analysis of the DNA of cancers linked to smoking, the scientists studied more than 5,000 tumors, comparing smokers' cancers with those of people who had never smoked.

They found specific molecular features of damage in the smokers' DNA, determined by the number of those mutations in different tumours.

Although the number of mutations within cancer cells varies between people, the new study identifies the additional "mutational load" tobacco smoking causes.

In other affected organs, the study shows smoking a pack a day causes an estimated average of 97 mutations in each cell of the larynx; 39 in the pharynx; 23 in the mouth; 18 in the bladder; and six mutations in every cell of the liver each year.

The research shows at least five distinct ways smoking damages DNA, the most common of which is found in most types of cancer: accelerating the speed of a cellular clock that appears to mutate DNA prematurely.

"Our research indicates that the way tobacco smoking causes cancer is more complex than we thought," Mike Stratton of Wellcome Trust Sanger Institute said.

"Indeed, we do not fully understand the underlying causes of many types of cancer," he added, pointing to other known causes, such as obesity.

But the new study of smoking-related cancers can help scientists better understand how all cancers develop and, possibly, how they can be prevented, Stratton said.

"The genome of every cancer provides a kind of 'archaeological record, in the DNA code, reflecting the exposure that causes mutations,” he added.

Smoking — the largest preventable cause of death — is responsible for at least six million deaths a year worldwide.

If current trends continue, the World Health Organisation says, smoking will kill more than a billion people in the 21st century.
A research team at Los Alamos National Laboratory quantifies the molecular damage inflicted on DNA and discloses that every 50 cigarettes smoked generates an average of one DNA mutation in each lung cell.