20 cigarettes daily for 1 year equals 150 lung cell mutations

 

In-depth genetic research gives new insight into how smoking is capable of causing cancer in such a wide array of organs. The study provides a link between the number of cigarettes smoked and the number of mutations in tumor DNA.

Smoking is a killer; new research uncovers its modus operandi.

The negative health consequences of smoking are well known and have been heavily studied.
An estimated 6 million people die each year due to smoking-related illnesses.
If trends continue, according to the World Health Organization (WHO), there will be 1 billion tobacco-related deaths this century.
Smoking is known to cause irreparable damage in a variety of organs. It sparks mutations in DNA via a number of mechanisms.
However, it has not been clear how cancer generates so many different types of cancers in disparate body parts. To date, smoking has been associated with 17 types of cancer, but the genetic mechanisms behind this have remained hidden.
Researchers from the Wellcome Trust Sanger Institute and King's College London in the United Kingdom and the Los Alamos National Laboratory, NM, recently undertook a deep dive into the genetics of smoking-related cancers. Their results are published this week in the journal Science.
In the most detailed investigation of its type, scientists delved into the the DNA of 5,000 tumors. They compared tumors from nonsmokers with tumors from smokers and examined any genetic differences. The analysis allowed them to understand the molecular fingerprints of smoking-related DNA damage.
The researchers were able to study these mutational signatures and count the number of mutations in each tumor.

Counting tobacco-related tumor mutations

Once the data was in, the authors could measure the rate of mutations caused per cigarette smoked. They found that smoking a pack of cigarettes per day caused a predictable average number of mutations in the lungs over the course of a year.
"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," says first author Dr. Ludmil Alexandrov, of the Los Alamos National Laboratory,.
"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."
The team also developed a clearer picture of the effects of cigarettes on mutations in other organs. They found that a pack a day led to:

• 97 mutations in each cell in the larynx
• 39 mutations in each cell in the pharynx
• 23 mutations in each cell in the mouth
• 18 mutations in each cell in the bladder
• 6 mutations in each cell in the liver.

As mentioned previously, how mutations affect organs of the body other than lungs has been difficult to understand. This new research uncovered ways in which tobacco can develop mutations in different tissues and organs.

"Mutations caused by direct DNA damage from carcinogens in tobacco were seen mainly in organs that come into direct contact with inhaled smoke. 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."

Study co-author Prof. David Phillips, King's College London

Of the five distinct processes by which DNA is damaged by tobacco smoke, the most widespread was one already found in other nonsmoking-related cancers. The team found that smoking accelerated the speed of a cellular clock that prematurely mutates DNA.

Looking into the future of cancer research

The researchers were surprised by some of the results; smoking-related cancers are more complex than previously thought.
Prof. Sir Mike Stratton, from the Wellcome Trust Sanger Institute and joint lead author, says: "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."
Medical News Today recently asked Dr. Alexandrov if they plan to carry out more research in a similar vein. He said:
"This study has shown that molecular profiling of cancer patients can be used to identify the mechanisms by which different carcinogens cause cancer. We are planning future studies to reveal the mechanisms by which other known epidemiological factors cause cancer. For example, we are currently working on elucidating the mechanisms by which obesity causes cancer.​"
When MNT asked him what research he would carry out if he was given unlimited time, money, and resources, he said: "I would molecularly profile every single cancer patient across the world to better understand the causes of cancer and use this knowledge for developing future cancer prevention strategies.​"
The current results mark a milestone along the path to understanding how smoking-related cancers negatively influence DNA. There is still much to know, but investigations such as this will steadily bring us closer to understanding and preventing cancer on a molecular level.
Learn how deadly brain cancer genes were identified.

Written by Tim Newman

 Research has found several risk factors that may increase your chances of getting lung cancer.

Smoking

Cigarette smoking is the number one risk factor for lung cancer. In the United States, cigarette smoking is linked to about 80% to 90% of lung cancers. Using other tobacco products such as cigars or pipes also increases the risk for lung cancer. Tobacco smoke is a toxic mix of more than 7,000 chemicals. Many are poisons. At least 70 are known to cause cancer in people or animals.
People who smoke cigarettes are 15 to 30 times more likely to get lung cancer or die from lung cancer than people who do not smoke. Even smoking a few cigarettes a day or smoking occasionally increases the risk of lung cancer. The more years a person smokes and the more cigarettes smoked each day, the more risk goes up.
People who quit smoking have a lower risk of lung cancer than if they had continued to smoke, but their risk is higher than the risk for people who never smoked. Quitting smoking at any age can lower the risk of lung cancer.
Cigarette smoking can cause cancer almost anywhere in the body. Cigarette smoking causes cancer of the mouth and throat, esophagus, stomach, colon, rectum, liver, pancreas, voicebox (larynx), trachea, bronchus, kidney and renal pelvis, urinary bladder, and cervix, and causes acute myeloid leukemia.

Secondhand Smoke

Smoke from other people’s cigarettes, pipes, or cigars (secondhand smoke) also causes lung cancer. When a person breathes in secondhand smoke, it is like he or she is smoking. In the United States, two out of five adults who don’t smoke and half of children are exposed to secondhand smoke, and about 7,300 people who never smoked die from lung cancer due to secondhand smoke every year.

Radon

Radon is a naturally occurring gas that comes from rocks and dirt and can get trapped in houses and buildings. It cannot be seen, tasted, or smelled. According to the U.S. Environmental Protection Agency (EPA), radon causes about 20,000 cases of lung cancer each year, making it the second leading cause of lung cancer. Nearly one out of every 15 homes in the U.S. is thought to have high radon levels. The EPA recommends testing homes for radon and using proven ways to lower high radon levels.

Other Substances

Examples of substances found at some workplaces that increase risk include asbestos, arsenic, diesel exhaust, and some forms of silica and chromium. For many of these substances, the risk of getting lung cancer is even higher for those who smoke.

Personal or Family History of Lung Cancer

If you are a lung cancer survivor, there is a risk that you may develop another lung cancer, especially if you smoke. Your risk of lung cancer may be higher if your parents, brothers or sisters, or children have had lung cancer. This could be true because they also smoke, or they live or work in the same place where they are exposed to radon and other substances that can cause lung cancer.

Radiation Therapy to the Chest

Cancer survivors who had radiation therapy to the chest are at higher risk of lung cancer.

Diet

Scientists are studying many different foods and dietary supplements to see whether they change the risk of getting lung cancer. There is much we still need to know. We do know that smokers who take beta-carotene supplements have increased risk of lung cancer.