For decades, lung cancer prevention has focused largely on encouraging people not to smoke and screening those with a significant smoking history.
While these strategies have saved lives, they do not explain why many people who have never smoked still develop lung cancer.
Scientists increasingly believe that environmental factors such as air pollution may play a major role, particularly in cities where people are exposed to traffic emissions, industrial pollution, and other airborne particles every day.
Researchers from University College London and the Francis Crick Institute have now reported a discovery that may help identify people at risk long before lung cancer develops. Their study, published in Cell, describes a blood-based protein signature that appears to reveal an inflammatory state in the lungs that comes before cancer.
The research began with a simple but important question. Why do some people develop lung cancer while others with similar genetic mutations do not?
Scientists have known for years that aging cells gradually accumulate mutations that can potentially cause cancer. Yet most mutated cells never become tumors. Researchers suspected that another factor must be involved.
Earlier work from the same team pointed to inflammation caused by air pollution. Pollution exposure can activate immune responses inside the lungs and create conditions that encourage damaged cells to grow abnormally. The scientists wanted to know whether this process leaves detectable signs in the bloodstream.
To investigate, they examined blood plasma samples from more than 48,000 people enrolled in the UK Biobank project. Using advanced machine-learning techniques, they searched for patterns among thousands of proteins. The goal was to identify proteins linked to future lung cancer.
The researchers eventually identified 14 proteins that together formed a powerful risk signature. People with higher levels of this signature were much more likely to develop lung cancer within the next five years. The signature remained predictive even after accounting for age, smoking status, and previous lung disease.
The discovery was not limited to one group of people. The team validated the signature across eight independent datasets involving researchers from multiple countries and continents. The same pattern consistently appeared in people who later developed lung cancer, including groups of non-smokers.
Further investigation suggested that the protein signature is not produced by cancer itself. Instead, it reflects ongoing inflammation and biological changes occurring in the lungs before a tumor forms. This finding is important because it opens a potential window for intervention before cancer becomes established.
The researchers also discovered a connection with KAC cells, a type of adaptive cell state that appears during lung injury.
Normally these cells help repair damaged tissue. However, when cancer-causing mutations are present, KAC cells may become a stepping stone toward cancer. Air pollution increased the number of these cells while simultaneously increasing the 14-protein signature.
A major player in this process appears to be the inflammatory molecule IL-1β. Experiments showed that air pollution stimulates IL-1β production, which in turn encourages the formation of KAC cells. When researchers blocked IL-1β in animal models, they observed fewer KAC cells and slower early tumor development.
The findings gained additional support from a previous human study known as the CANTOS trial. This trial tested canakinumab, a drug that blocks IL-1β.
While originally developed for cardiovascular disease, the medication unexpectedly reduced lung cancer rates. By reexamining the data, researchers found that patients with the highest 14-protein signature benefited the most from treatment.
This suggests a future in which doctors could use a simple blood test to identify people with dangerous lung inflammation and offer targeted preventive therapy. Such an approach would be similar to how cholesterol testing identifies people who may benefit from statins to prevent heart disease.
Analysis of the findings indicates that this study provides one of the strongest pieces of evidence so far linking air-pollution-related inflammation to lung cancer development. The combination of human data, machine-learning analysis, international validation, and animal experiments creates a compelling scientific case.
However, the protein signature is not yet ready for clinical use, and further studies will be needed to confirm its accuracy and determine the best prevention strategies.
If future research succeeds, this work could transform lung cancer prevention by identifying high-risk individuals years before the disease begins and giving doctors a chance to stop cancer before it starts.
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The research was published in Cell.
Source: University College London.
