Lung cancer is the tumor that causes the most deaths in men in Spain, and the second in the case of women, since the list of most lethal neoplasms among the female population is headed by breast cancer, according to data from the Spanish Society of Pneumology and Thoracic Surgery (SEPAR). Although this disease is directly linked to smoking, experts warn that more and more people are developing lung cancer without ever having smoked and now the reason has been discovered.
A group of scientists has verified that exposure to fine PM2.5 particles (so called because they are smaller than 2.5 microns) present in the air we breathe, and which come from traffic emissions and other sources of environmental pollution , can promote the proliferation of gene mutations specific to lung cancer that an individual has and trigger this type of cancer or contribute to further tumor progression.
The findings have been published in Nature and help to understand how pollution interacts with lung cells to initiate and extend the changes that ultimately cause cancer and offer an explanation for cases of lung cancer in non-smokers, also providing a new argument to promote initiatives that improve air quality to protect public health.
Globally, more people are exposed to dangerous levels of air pollution than to toxic chemicals from cigarette smoke
Air pollution has been associated with the appearance or aggravation of many health problems, from asthma to cardiovascular diseases, or Alzheimer’s, among others, and Charles Swanton, director of the Francis Crick Institute and research and one of the authors of the new A study has warned that it is only necessary to be exposed to pollution between three and five years to activate the mechanism that triggers lung cancer.
“The same airborne particles derived from the combustion of fossil fuels that exacerbate climate change are directly impacting human health through an important and previously overlooked cancer-causing mechanism in lung cells. The risk of lung cancer from air pollution is less than from tobacco use, but we have no control over what we all breathe. Globally, more people are exposed to dangerous levels of air pollution than to toxic chemicals from cigarette smoke, and these new data link the importance of addressing climate health to improving human health,” said Swanton. .
The interaction between environmental and genetic factors causes cancer
The researchers studied data from more than 400,000 people to determine whether rates of some types of lung cancer were higher in areas with high levels of fine PM2.5 particles, which, because of their small size, easily reach the lungs.
First, they investigated the relationship between PM2.5 exposure and the frequency of lung cancer in 32,957 people with EGFR-mutant lung cancer residing in England, Taiwan, South Korea, and Canada and found that exposure to Elevated PM2.5 levels are associated with an increased estimated incidence of EGFR-mutated lung cancer. They found that this association was consistent with data from 407,509 individuals registered in the UK Biobank.
They then examined a group of 228 people with lung cancer in Canada and found that there was a higher frequency of lung cancer cases after three years of high exposure to PM2.5 air pollutants (73%) compared to a low exposure (40%). They used mouse models to investigate the cellular processes that might underlie the mechanism that induced lung cancer in non-smokers in relation to polluted air.
More than seven decades ago, it had been established that the genesis of tumors occurred in two phases, an initial one in which mutations were induced in healthy cells, followed by another that promoted the development of cancer, but these researchers have verified that this is not the case. . Swanton has explained that environmental PM2.5 particles drive lung cancer by acting on cells in healthy lung tissue that have pre-existing oncogenic mutations. “In EGFR-induced lung cancer, which is more common in never-smokers or light smokers, we found a significant association between PM2.5 levels and lung cancer incidence in 32,957 lung cancer cases. EGFR-induced lung in four cohorts within the country”.
They have also found that PM2.5 particles seem to trigger a process in the immune system: it drives the entry of macrophages that release the inflammatory mediator, interleukin-1β, which drives the expansion of cells with EGFR mutations in response to PM2.5 exposure, and that interleukin-1β blockade inhibits lung cancer initiation. This process, he explains, generates a progenitor-like cellular state within EGFR-mutant type II lung alveolar epithelial cells that fuels tumorigenesis, “exacerbating inflammation and further driving tumor progression in cancer models.” EGFR and KRAS”.
Speaking to SMC Spain, Víctor Briz, Ramón y Cajal Researcher at the National Center for Environmental Health of the Carlos III Health Institute, stressed that “the importance and significance of this study lies not only in confirming with reliable statistical data this association between pollution and the development of lung tumors, but in that it goes further, by investigating and elucidating the mechanisms involved using animal models. Using genetically modified mouse models, the authors convincingly demonstrate that air pollution particles trigger an inflammatory response in the lungs, mediated by macrophages (immune system cells) and interleukin-1 (proinflammatory molecule), which is responsible for to stimulate the proliferation of certain cells of the lung epithelium (precisely those with EGFR mutations)”.
“They also show that these types of mutations accumulate naturally with age and are not the result of other environmental factors (such as tobacco or pollution itself) and, therefore, all people are susceptible to them. ; hence the importance of reducing levels of environmental pollution. Although the authors acknowledge small methodological limitations in their study, such as estimates of particle exposure by region (rather than individual exposure) or the use of previously unpurified alveolar tissue of different cell types in genetic analyses, These are minimal compared to the overwhelming scientific evidence provided that supports their conclusions.
Fountain: Francis Crick Institute
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