This is such an important subject that the organizers of the major oncology congress being held this weekend in Paris have chosen to present it at the opening of their first plenary conference. No revolutionary treatment yet, but a study showing that fine particle pollution is indeed the cause of lung cancers that sometimes appear in non-smokers. If a correlation could have been established for a long time, until now a causal mechanism was missing. “There could be confounding factors, the pollution could mask the real cause. But now we know that this is not the case, there is indeed a direct link”, explains to L’Express Charles Swanton, researcher at Francis Crick Institute and lead author of the study.
For oncologists, still too often helpless in the face of this formidable killer, this demonstration represents a powerful invitation for the public authorities to act to reduce this pollution, particularly due to road traffic. “This is essential because the incidence of lung cancer in non-smokers is increasing all over the world, especially in women”, underlines Dr. Suzette Delaloge, oncologist at Gustave-Roussy, who did not participate in the study. According to various estimates, this disease currently kills around 300,000 people a year worldwide. And if the individual risk of developing lung cancer because of pollution is much lower than that linked to cigarettes, it concerns a large part of the population, involuntarily exposed to these particles – they are “silent killers”, insists Charles Swanton.
The culprit: inflammation
“Traditionally, cancer is said to be caused by genetic mutations in cells. But that model didn’t work here, because fine particles don’t directly lead to mutations in lung cells. these tumors are very common, and yet not everyone develops cancer. So there was necessarily something else”, recalls the scientist. It took him ten years of research, international collaborations and advanced techniques to find what it is: the inflammation due to these pollutants.
He first reconfirmed the epidemiological association between increased concentrations of fine particles and increased risk of cancer, thanks to data on more than 400,000 people in the United Kingdom, Taiwan and South Korea. Next, his team analyzed lung biopsies from normal and diseased patients. While all carried the mutations found in cancers, only the patients presented an inflammatory reaction in the lungs. “The particles cause the arrival of macrophages which will release an interleukin, IL1-beta. This molecule will push a certain type of lung cells to transform into stem cells, capable of proliferating. And if this happens in carrier cells of a mutation in an oncogene, then the tumor process begins”, explains the researcher.
A mechanism confirmed in the laboratory, by the study of mice, carriers or not of the mutated gene, and exposed or not to pollution. “Cancers were much more frequent in mice both carrying the mutations and exposed to pollution”, details Charles Swanton. He also showed in animal models that if interleukin is blocked, then mice, even with the mutation and exposed to the particles, will not have a tumour. These results are all the more interesting since it has also been shown that in humans, the administration of an anti-interleukin IL1-beta reduces the risk of cancer. Indeed, in 2017, a laboratory carried out a clinical trial where this molecule was given to patients to prevent the onset of cardiovascular disease. “The American health authorities asked that the patients be followed long enough to verify that the treatment did not induce tumours. But the opposite happened!”, says the researcher again. Could we, tomorrow, prevent the appearance of tumors by giving a simple drug to individuals most exposed to air pollution? “Why not, especially if we can’t reduce air pollution, exclaims the researcher. After all, we give many statins and aspirin to prevent heart attacks”.
Vaping and pollution, same risks?
Until that happens, however, we will have to find a way to target the individuals most at risk, which remains a challenge today. For this, many questions remain to be resolved. For example, why do mutations appear if they are not due to pollution? “Is it just related to ageing, or are there other reasons?” asks Suzette Delaloge. It will also be necessary to explain why all individuals carrying a mutation and exposed to pollution do not systematically fall ill – are there protective factors, for example? “We also want to understand why interleukin acts on certain cells and not on others, and especially why it modifies these cells. This will occupy us over the next few years”, assures Charles Swanton.
More broadly, the researcher wonders if this mechanism could not also explain some of the lung cancers in smokers. “Generally, it causes specific mutations, but these are absent in 10% of tumors caused by tobacco”, indicates Charles Swanton, who says he is especially worried about vapers.
“The smoke emitted by electronic cigarettes could very well have the same effect as pollution in non-smokers. We lack hindsight on this subject,” he explains. Above all, his work pleads for further research on other environmental pollutants considered to be carcinogens. Too often, the absence of a demonstrated causal relationship justifies inaction. Here too, uncovering mechanisms would give irrefutable arguments to health authorities to better protect the population.