Tuesday, November 8, 2016

Smoking causes hundreds of genetic mutations

NHS: "Research quantifies genetic damage caused by smoking," the Mail reports, saying a pack a day causes 150 mutations in lung cells. This study analysed the DNA sequence of cells from more than 5,000 cancers. About half came from smokers and the rest from non-smokers, which allowed researchers to compare mutations between the two.

Overall, the study found cancer cells from smokers tended to contain a higher number of mutations and abnormal substitutions in the DNA sequence.
The researchers were able to estimate the number of mutations that would be caused in different types of cells – not just in the lung – from smoking one pack a day for one year.
For example, one year's smoking would cause 150 mutations in lung cells, 97 mutations in cells of the voice box (larynx), and 39 in the throat (pharynx).
As the researchers say, their genetic analysis isn't able to tell for certain the mechanism by which these changes occur, or know whether other behaviours associated with smoking, such as drinking alcohol, may be involved in the changes.
Nevertheless, the study highlights the known harms of tobacco smoking and the mix of cancer-causing chemicals cigarettes contain. Any amount of smoking may be harmful, but it's never too late to stop.

Where did the story come from?

The study was carried out by researchers from Los Alamos National Laboratory and the University of New Mexico Comprehensive Cancer Center, both in the US, and various other international institutions.
It was funded by the Wellcome Trust, among other sources, and was published in the peer-reviewed journal Science. The article is openly available to access online.
The media gave reliable coverage of this study overall.

What kind of research was this?

This genetic study aimed to analyse the DNA mutations found in thousands of different types of cancer cells that are linked with smoking.
Smoking is well known to be harmful to health. It's said to be associated with 17 different types of cancer and behind the cause of death for six million people worldwide every year.
Of the chemicals in tobacco, 60 of them are reported to be known cancer-causing substances (carcinogens).
Many of them cause DNA damage and gene mutations in body cells that then replicate to result in large numbers of abnormal cells. 
This study aimed to analyse the different genetic mutations caused by tobacco smoke.

What did the research involve?

The study examined the DNA sequences in 5,243 cell samples from cancers linked to smoking. The samples included lung, mouth, throat, liver, kidney, bladder, pancreatic and cervical cancers.
The researchers focused on analysing the particular positions within the DNA sequence of these cells where mutations were occurring, called mutational signatures.
Of the samples, 2,490 were reported to come from smokers and 1,062 from never-smokers, so they were able to compare the number and type of mutations found in smokers with non-smokers.

What were the basic results?

The researchers found that in smokers there were a greater number of instances where points in the DNA sequence had been substituted, in particular for lung, throat, liver and kidney cancers. 
Smokers had a greater number of mutations within certain mutational signatures than non-smokers. For example, most lung and throat cancers from smokers had many mutations in signature 4. 
However, 13.8% of non-smokers also showed many signature 4 mutations, which the researchers speculate could be down to passive smoking or past non-reported smoking habits.
The researchers went on to describe the other individual mutational signatures where they found differences for smokers versus non-smokers, including signatures 2, 5, 13 and 16. 
They then used this information on mutational signatures by cancer type to calculate the age-adjusted risk of a person who smokes 30 or more cigarettes a day developing specific cancers. 
For example, a male smoker was 22 times more likely to develop the most common type of lung cancer (adenocarcinoma) and 13 times more likely to develop cancer of the larynx. A woman had almost double the risk of cervical and ovarian cancers.
The researchers calculated that the number of abnormal substitutions in the DNA sequence increased with the number of pack years smoked – one pack year meaning smoking one pack of cigarettes a day for one year.
They estimated one pack year smoked would cause 150 mutations in lung cells, 97 mutations in cells of the larynx, 39 in the pharynx, 23 in the mouth, 18 in the bladder, and 6 mutations in liver cells.

How did the researchers interpret the results?

The researchers concluded that their results are consistent with the theory that smoking causes cancer by increasing the number of mutations found in the cellular DNA, though the exact mechanism by which this happens isn't completely clear.
They said: "Although we cannot exclude roles for covariate behaviours of smokers or differences in the biology of cancers arising in smokers compared with non-smokers, smoking itself is most plausibly the cause of these differences."


This study serves to highlight the known harms of cigarette smoking. The research benefits from analysing thousands of different cancer cell lines, and carefully comparing the mutations found in smokers with those of non-smokers.
It shows that there are differences between the two – even in cancers of the same type – with those from smokers generally tending to have a higher number of mutations and abnormal substitutions in the DNA sequence. 
However, it can't tell us much more than that. For example, it can't tell us whether the same cell type and stage of lung cancer in a smoker is likely to have a poorer prognosis than the same cancer in a non-smoker because it contains more mutations.
As the researchers acknowledge, they can't tell from this study the exact biological mechanisms that may be causing the mutations in smokers and non-smokers, or know whether other smoking-related behaviours, such as alcohol consumption, may have an influence.
It's also important to emphasise that the number of mutations caused per pack year smoked are very general estimates based on only this single dataset.
For example, we can't know for definite that a man who has smoked one pack a day for 20 years now has 3,000 mutations in his lung cells.
The amount of DNA damage caused by smoking in any individual may be greatly influenced by their underlying genetic profile, lifestyle, environment, and the type of tobacco smoked.
Nevertheless, this study highlights the known harms of tobacco smoking and the mix of cancer-causing chemicals that cigarettes contain. Any amount of smoking may be harmful, but it's never too late to stop.