Twenty cigarettes daily for 1 year equals 150 lung cell mutations

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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.
[Man stubbing out cigarette]
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.

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