Protective cells could cut risk of lung cancer for ex-smokers

The study, funded by Cancer Research UK, discovered that people who had stopped smoking had more genetically healthy lung cells, which have a much lower risk of developing into cancer.

Published in Nature, the research found that quitting smoking could do much more than just stopping further damage to the lungs. Researchers believe it also allows new, healthy cells to actively replenish the lining of our airways. This shift in proportion of healthy to damaged cells could help protect against cancer.

These results highlight the benefits of stopping smoking completely, at any age.

Genetic mutations caused by smoking 

First author, Dr Kate Gowers (Lungs for Living Research Centre at UCL), said: “Our study is the first time that scientists have looked in detail at the genetic effects of smoking on individual healthy lung cells.

“We found that even these healthy lung cells from smokers contained thousands of genetic mutations. These can be thought of as mini time-bombs waiting for the next hit that causes them to progress to cancer.

“Further research with larger numbers of people is needed to understand how cancer develops from these damaged lung cells.”

Lung cancer is the most common cause of cancer death in the UK, accounting for 21% of all cancer deaths. Smoking tobacco damages DNA and hugely increases the risk of lung cancer, with around 72% of the 47,000 annual lung cancer cases in the UK caused by smoking.

DNA damage

Damage to the DNA in cells lining the lungs creates genetic errors, and some of these are ‘driver mutations’, which are changes that give the cell a growth advantage. Eventually, an accumulation of these driver mutations can let the cells divide uncontrollably and become cancerous. However, when someone stops smoking, they avoid most of the subsequent risk of lung cancer.

In the first major study of the genetic effects of smoking on ‘normal’, non-cancerous lung cells, researchers analysed lung biopsies from 16 people including smokers, ex-smokers, people who had never smoked and children.

They sequenced the DNA of 632 individual cells from these biopsies and looked at the pattern of genetic changes in these non-cancerous lung cells.

The researchers found that despite not being cancerous, more than nine out of every 10 lung cells in current smokers had up to 10,000 extra genetic changes – mutations – compared with non-smokers, and these mutations were caused directly by the chemicals in tobacco smoke. More than a quarter of these damaged cells had at least one cancer-driver mutation, which explains why the risk of lung cancer is so much higher in people who smoke.

Reducing the risk of lung cancer

Unexpectedly, in people who had stopped smoking, there was a sizable group of cells lining the airways that had escaped the genetic damage from their past smoking. These cells looked like they came from people who had never smoked: they had much less genetic damage from smoking and would have a low risk of developing into cancer.

The researchers found that ex-smokers had four times more of these healthy cells than people who still smoked – representing up to 40% of the total lung cells in ex-smokers.

While the study showed that these healthy lung cells could start to repair the lining of the airways in ex-smokers and help protect them against lung cancer, smoking also causes damage deeper in the lung that can lead to emphysema – chronic lung disease. This damage is not reversible, even after stopping smoking.

Joint senior author, Professor Sam Janes (UCL Medicine & University College London Hospitals Trust), said: “Our study has an important public health message and shows that it really is worth quitting smoking to reduce the risk of lung cancer. Stopping smoking at any age does not just slow the accumulation of further damage, but could reawaken cells unharmed by past lifestyle choices. Further research into this process could help to understand how these cells protect against cancer, and could potentially lead to new avenues of research into anti-cancer therapeutics.”

Never too late to stop smoking

Joint senior author, Dr Peter Campbell (Wellcome Sanger Institute), said: “People who have smoked heavily for 30, 40 or more years often say to me that it’s too late to stop smoking – the damage is already done. What is so exciting about our study is that it shows that it’s never too late to quit – some of the people in our study had smoked more than 15,000 packs of cigarettes over their life, but within a few years of quitting many of the cells lining their airways showed no evidence of damage from tobacco.”

This research is part of the £20 million Mutographs of Cancer project, a Cancer Research UK Grand Challenge initiative. The project detects DNA ‘signatures’ that indicate the source of damage, to better understand the causes of cancer, and discover the ones we may not yet be aware of.

Dr Rachel Orritt (Cancer Research UK), said: “It’s a really motivating idea that people who stop smoking might reap the benefits twice over - by preventing more tobacco-related damage to lung cells, and by giving their lungs the chance to balance out some of the existing damage with healthier cells. What’s needed now are larger studies that look at cell changes in the same people over time to confirm these findings.

“The results add to existing evidence that, if you smoke, stopping completely is the best thing you can do for your health. It’s not always easy to kick the habit, but getting support from a free, local Stop Smoking Service roughly triples the chance of success compared to going it alone.”

Further information

• Research paper published in Nature
• Dr Kate Gowers’s academic profile
• Professor Sam Janes’ academic profile
• Lungs for Living Research Centre at UCL
• UCL Medicine
• Wellcome Sanger Institute
• Cancer Research UK
• Main image: Infographic ‘Why it’s never too late to stop smoking’: Credit Wellcome Sanger Institute
• Media contact: Henry Killworth +44 (0) 207 679 5296 h.killworth@ucl.ac.uk