Lung cancer remains one of the leading causes of cancer deaths worldwide. One reason it is so deadly is that it is often discovered only after it has already spread.
By the time symptoms appear, treatment can be difficult and survival rates are much lower. Doctors currently offer lung cancer screening mainly to older adults with a history of smoking.
While this approach helps many people, it can miss others who are also at risk, including lifelong non-smokers exposed to air pollution.
Now, researchers from University College London (UCL), the Francis Crick Institute, and their international collaborators have made a discovery that may one day help doctors identify people at risk of lung cancer years before the disease develops. Their findings were published in the journal Cell.
The research builds on earlier studies showing that air pollution does more than damage the lungs. Scientists previously discovered that pollution can trigger inflammation inside the lungs and awaken dormant cells that already carry cancer-causing mutations. As people age, these mutations naturally accumulate in many tissues throughout the body.
However, having mutations alone is often not enough to cause cancer. Researchers believe that environmental triggers such as air pollution, cigarette smoke, and other airborne pollutants may push these damaged cells toward becoming cancerous.
In the new study, scientists wanted to find a way to detect this harmful inflammatory state before cancer appears. They analyzed blood samples from more than 48,000 participants in the UK Biobank, one of the world’s largest long-term health studies.
Using machine learning, a form of artificial intelligence that can identify patterns in large amounts of data, the researchers searched for proteins in the blood linked to future lung cancer.
The analysis revealed a group of 14 proteins that could predict whether a person would develop lung cancer within the following five years. The researchers combined these proteins with information such as age, smoking status, and previous lung disease. Together, they created a signature that accurately identified people at higher risk.
The team then tested the signature in eight different datasets from around the world. In every study, people who later developed lung cancer had higher levels of the protein signature before their diagnosis. Remarkably, this was true even among non-smokers.
The researchers found evidence that the signature does not come from an existing tumor. Instead, it appears to reflect an unhealthy inflammatory environment inside the lungs that exists before cancer begins.
The same signature was also found in people who later developed chronic lung diseases such as chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis.
To understand why this happens, scientists studied mice exposed to air pollution. They discovered that pollution increased both the 14-protein signature and the number of special cells called KAC cells.
These cells normally appear when the lungs are injured and need repair. However, if cancer-causing mutations are already present, KAC cells can become a starting point for cancer development.
The researchers also found that air pollution stimulates the production of an inflammatory molecule called interleukin-1 beta, or IL-1β. This molecule appears to play a key role in expanding KAC cells and promoting cancer development. When the researchers blocked IL-1β in mice, fewer KAC cells formed and early tumor growth slowed.
These findings connect with an earlier clinical trial called CANTOS, which tested the drug canakinumab, an IL-1β blocker. Although the original trial focused on heart disease, researchers noticed that patients receiving the drug developed less lung cancer.
In the new study, scientists reanalyzed data from more than 4,600 participants and discovered that people with high levels of the 14-protein signature received the greatest benefit. Their risk of lung cancer was nearly cut in half.
The findings suggest that the protein signature could one day help doctors identify people who may benefit from preventive treatment before cancer develops. Instead of waiting for tumors to appear, doctors might be able to intervene earlier when disease is still preventable.
Analysis of the findings suggests this research could represent an important shift in cancer prevention. Rather than focusing only on detecting existing tumors, scientists are moving toward identifying biological changes that occur years before cancer forms.
The study is strengthened by its large sample size, international validation, and supporting laboratory experiments. However, more clinical trials will be needed before the blood test or preventive treatments become part of routine care.
If confirmed, this approach could expand lung cancer prevention beyond smokers and help protect many people exposed to pollution and other environmental risks.
If you care about lung health, please read studies about marijuana’s effects on lung health, and why some non-smokers get lung disease and some heavy smokers do not.
For more information about health, please see recent studies that olive oil may help you live longer, and vitamin D could help lower the risk of autoimmune diseases.
The research was published in Cell.
