Quitting Smoking can Reduce Risk of Lung Cancer

Quitting smoking reduces the risk of lung cancer in ex-smokers due to protective cells present in the lungs, reveals a new study conducted by scientists at the Wellcome Sanger Institute and University College London (UCL), UK. This ground-breaking research, published in the prestigious journal Nature, found that people who had quit smoking, had genetically healthier lung cells compared to current smokers. Consequently, smokers who had quit were much less likely to develop lung cancer

The research is part of the Mutographs Project, supported by a £20 million grant from Cancer Research UK’s Grand Challenge Initiative. The researchers found that ‘DNA Signatures’ were capable of pin-pointing the exact location of the lung damage, which helped to develop a better understanding of the molecular basis of the pathogenesis of lung cancer.

Study Team

The study was jointly led by Dr. Peter Campbell, PhD and Dr. Samuel Janes, MBBS, MSc, PhD. Dr. Campbell is the Head of Cancer, Aging and Somatic Mutation, and Senior Group Leader at the Wellcome Sanger Institute, Hinxton, UK. He is also a practicing Hematologist at Addenbrooke’s Hospital, Cambridge, UK.

Dr. Janes is a Professor of Respiratory Medicine at the Lungs for Living Research Center in the Division of Medicine, UCL, London, UK. The co-lead author of the paper was Dr. Kate Gowers, PhD, who is a Research Project Manager in Janes’ Lab.

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Lung Cancer & its Pathogenesis

Lung cancer is one of the leading causes of cancer deaths worldwide. In the UK, it is the most common form of cancer, which accounts for 21 percent of all cancer deaths. The risk of lung cancer significantly increases from exposure to tobacco smoke, which damages DNA (deoxyribonucleic acid) due to the occurrence of mutations (alterations) in the DNA strands.

Importantly, smoking is responsible for approximately 72 percent of the 47,000 lung cancer cases diagnosed annually in the UK. It is also alarming to note that in the US, approximately 229,000 lung cancer cases will be detected by the end of this year.

It has been discovered that DNA damage in cells lining the lungs can produce genetic errors that can lead to ‘driver mutations’, which are so called because they ‘drive’ the pathogenesis of cancer. This occurs due to the progressive accumulation of mutations in the DNA – brought about by excessive smoking – which stimulates the cells to divide uncontrollably, thereby making them cancerous. However, quitting smoking appreciably reduces the risk of developing lung cancer.

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Key Features of the Study

• First study to evaluate the genetic effects of smoking on normal, healthy, non-cancerous lung cells
• 16 participants were included in the study
• Participants were categorized into the following:
• Current smokers
• Ex-smokers
• Never smokers
• Children
• Lung biopsies were taken from all the participants and subjected to genetic analysis
• DNA from 632 individual cells obtained from the biopsy tissue samples were sequenced
• Alterations in the genetic patterns in these non-cancerous lung cells were analyzed

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Key Findings of the Study

• 9 out of 10 non-cancerous lung cells of current smokers harbored up to 10,000 extra mutations compared to non-smokers
• The mutations were caused by carcinogenic chemicals present in tobacco smoke
• Over one-fourth of the damaged lung cells had at least one cancer-driver mutation
• Majority of lung cells in ex-smokers remained undamaged from their past smoking
• These lung cells of ex-smokers were genetically identical to those present in people who had never smoked
• Ex-smokers had 4-times more of these healthy lung cells, compared to those of current smokers
• These healthy lung cells of ex-smokers accounted for 40 percent of total lung cells

Gowers indicates: “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.”

Word of Caution – Quitting Smoking May Not Always Help!

Although the present study clearly shows that the healthy lung cells are capable of repairing the lining of the airways in ex-smokers; this is limited to the cellular surface layer only. Notably, chain-smokers can sustain severe damage to the deeper tissue layers of the lungs, often leading to chronic respiratory disease. This damage is irreparable and irreversible, even after quitting smoking. Hence, there is a need to exercise caution.

Future Plans

The research team are planning to carry out a larger study, involving a higher number of participants in order to elucidate the mechanism of carcinogenesis in DNA-mutated lung cells, arising from smoking.

Expert Comments

Campbell says: “What’s 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.”

Dr. Rachel Orritt, PhD, who is a Health Information Manager at Cancer Research UK, says: “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.”

Concluding Remarks

Janes concludes: “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.”

Funding Source

The study was funded by Cancer Research UK, which is a cancer research and awareness charity based in London, UK.

References:

1. Tobacco Smoking and Somatic Mutations in Human Bronchial Epithelium - (http://dx.doi.org/10.1038/s41586-020-1961-1)
2. Never Too Late to Quit: Protective Cells Could Cut Risk of Lung Cancer for Ex-Smokers - (https://www.cancerresearchuk.org/about-us/cancer-news/press-release/2020-01-29-never-too-late-to-quit-protective-cells-could-cut-risk-of-lung-cancer-for-ex-smokers)

Source-Medindia