It’s possible that I shall make an ass of myself. But in that case one can always get out of it with a little dialectic. I have, of course, so worded my proposition as to be right either way (K.Marx, Letter to F.Engels on the Indian Mutiny)
INTERNATIONAL ASSOCIATION FOR THE STUDY OF LUNG CANCER
(Denver Sept. 9, 2021 9 a.m. GMT/10 a.m. CDT/11 a.m. EDT)—Five European countries rank highest for lung cancer risk among those aged 50 to 69 years attributable to air pollution, according to research presented in today’s Presidential Symposium Plenary Session at the IASLC 2021 World Conference on Lung Cancer.
Although tobacco smoke is clearly a major cause of lung cancer, a recent analysis determined that worldwide, air pollution accounts for 14% of lung cancers, according to data reported by Christine Berg.
The causal evidence of a link between air pollution and lung cancer has been building for decades, but the risk varies widely in different regions of the world, depending on the age of the population, the amount of tobacco smoking over time, and the amount of air pollution in the country. Berg and co-researcher Dr. Joan Schiller, an adjunct professor at the University of Virginia and a Board Member of the Lung Cancer Research Foundation, sought to better understand the worldwide variability in air pollution attributable to lung cancer.
Berg conducted a review of the literature on the burden of indoor and outdoor air pollution. She assessed the burden of lung cancer by country from air pollution by querying The Global Burden of Disease Compare publicly accessible database. Lung cancer mortality was chosen as the endpoint in an age-standardized population of 100,000. Because the incidence of lung cancer increases with age, two age groups were selected: ages 50-69 and 70 and older. Both genders were combined in the analysis. Berg ranked the top 15 countries in each age group and compared changes in relative country ranking by age group.
According to her analysis, Serbia (36.88 per 100,000), Montenegro (34.61 per 100,000), North Macedonia (30.67 per 100,000), Bosnia/Herzegovina (30.64 per 100,000), and Poland (27.97 per 100,000) ranked highest for risk of lung cancer attributable to air pollution among ages 50-69.
Among the 70 and older group, China (98.55 per 100,000), Mongolia (71.11 per 100,000), North Korea (63.45 per 100,000), Laos (62.07 per 100,000), and Montenegro (61.80 per 100,000) ranked highest.
“For comparison, in the United States the number of lung cancer deaths per 100,000 attributed to air pollution in ages 50 to 69 is 3.91 and is 13.62 for 70 and older,” Berg said. The Balkans, Poland, Turkey, China, and some southeast Asian countries have the highest attributable risks. Serbia had the highest number of attributable deaths in the 50-69 age group, whereas China had the highest in the 70 and older age group.
“Patterns of cigarette smoking and amounts of pollution from fossil fuel energy sources are most likely the primary drivers of the variability in risk attributable to lung cancer,” said Berg. “As the tobacco epidemic is addressed, we also need to address other preventable causes of lung cancer.”
About the IASLC:
The International Association for the Study of Lung Cancer (IASLC) is the only global organization dedicated solely to the study of lung cancer and other thoracic malignancies. Founded in 1974, the association's membership includes nearly 7,500 lung cancer specialists across all disciplines in over 100 countries, forming a global network working together to conquer lung and thoracic cancers worldwide. The association also publishes the Journal of Thoracic Oncology, the primary educational and informational publication for topics relevant to the prevention, detection, diagnosis, and treatment of all thoracic malignancies. Visit www.iaslc.org for more information.
About the WCLC:
The WCLC is the world’s largest meeting dedicated to lung cancer and other thoracic malignancies, attracting more than 7,000 researchers, physicians and specialists from more than 100 countries. The goal is to increase awareness, collaboration and understanding of lung cancer, and to help participants implement the latest developments across the globe. The conference will cover a wide range of disciplines and unveil several research studies and clinical trial results. For more information, visit https://wclc2021.iaslc.org/.
SUBJECT OF RESEARCH
People
Tuesday, September 13, 2022
'Hidden Killer': Experts Urge Action After Study Shows How Air Pollution Causes Lung Cancer
"If you want to address human health, you have to address climate health first," said Charles Swanton, who led the research team. Steam rises from the cooling towers of the Jänschwalde lignite-fired power plant—which is to be taken off the grid and shut down by 2028 as Germany phases out coal—on January 6, 2022.
(Photo: Patrick Pleul/dpa-Zentralbild/picture alliance via Getty Images)
Experts emphasized the importance of more ambitiously addressing air pollution from fossil fuels after the presentation of a new breakthrough on lung cancer in Paris on Saturday.
"The same particles in the air that derive from the combustion of fossil fuels, exacerbating climate change, are directly impacting human health."
Scientists at the Francis Crick Institute and University College London (UCL) shared their findings—part of the TRACERx lung study funded by Cancer Research U.K.—at the annual conference of the European Society for Medical Oncology (ESMO).
"Our study has fundamentally changed how we view lung cancer in people who have never smoked," said Cancer Research U.K. chief clinician Charles Swanton, who led and presented the research.
The way air pollution causes cancer differs from cigarettes and sunlight. Tobacco smoke and ultraviolet light damage the structure of DNA, creating mutations that cause cancer. Air pollution causes inflammation in the lungs, affecting cells that carry mutations.
"Cells with cancer-causing mutations accumulate naturally as we age, but they are normally inactive," Swanton explained. "We've demonstrated that air pollution wakes these cells up in the lungs, encouraging them to grow and potentially form tumors."
The team analyzed 463,679 individuals from England, South Korea, and Taiwan, and examined lung tissue samples from humans and mice following exposure to particulate matter, or PM2.5—air particles that are no larger than 2.5 micrometers in diameter.
They found higher rates of epidermal growth factor receptor (EGFR) mutant lung cancer—and other types of cancers—in people who lived in areas with higher levels of PM2.5 pollution. They also found that, at least in mice, blocking a molecule which causes inflammation and is released in response to PM2.5 exposure prevents cancers from forming.
"According to our analysis, increasing air pollution levels increases the risk of lung cancer, mesothelioma, and cancers of the mouth and throat," noted Emilia Lim, co-first author and postdoctoral researcher at the Francis Crick Institute and UCL. "This finding suggests a broader role for cancers caused by inflammation triggered by a carcinogen like air pollution."
"Even small changes in air pollution levels can affect human health," she said, adding that 99% of the global population lives in areas that exceed annual World Health Organization (WHO) limits for PM2.5, "underlining the public health challenges posed by air pollution across the globe."
The WHO—when updating guidelines on air quality last September for the first time in over 15 years—warned that "the burden of disease attributable to air pollution is now estimated to be on a par with other major global health risks such as unhealthy diet and tobacco smoking, and air pollution is now recognized as the single biggest environmental threat to human health."
While most of the human population is exposed to unhealthy levels of air pollution—which is tied to other health issues including asthma, chronic obstructive pulmonary disease (COPD), dementia, and heart disease—research has repeatedly shown it's often worse in the poorest communities.
One 2021 study found that air pollution reduces the average global citizen's life by over two years. Citing an estimate that it is tied to more than eight million deaths worldwide per year, Swanton called air pollution a "hidden killer," according to Agence France-Presse.
Swanton stressed in a statement that "the same particles in the air that derive from the combustion of fossil fuels, exacerbating climate change, are directly impacting human health via an important and previously overlooked cancer-causing mechanism in lung cells."
"As consumption of fossil fuels goes hand in hand with pollution and carbon emissions, we have a strong mandate for tackling these issues."
"The risk of lung cancer from air pollution is lower than from smoking, but we have no control over what we all breathe," the scientist said. "Globally, more people are exposed to unsafe levels of air pollution than to toxic chemicals in cigarette smoke, and these new data link the importance of addressing climate health to improving human health."
"It's a wake-up call on the impact of pollution on human health," he told The Guardian. "You cannot ignore climate health. If you want to address human health, you have to address climate health first."
Tony Mok of the Chinese University of Hong Kong, who was not involved in the study, similarly said in a statement that "as consumption of fossil fuels goes hand in hand with pollution and carbon emissions, we have a strong mandate for tackling these issues—for both environmental and health reasons."
Like the scientists who conducted the study, Mok also pointed out how it could help with the prevention of lung cancer among nonsmokers.
"This research is intriguing and exciting as it means that we can ask whether, in the future, it will be possible to use lung scans to look for pre-cancerous lesions in the lungs and try to reverse them with medicines," Mok said.
"We don't yet know whether it will be possible to use highly sensitive EGFR profiling on blood or other samples to find nonsmokers who are predisposed to lung cancer and may benefit from lung scanning," he added, "so discussions are still very speculative."
Suzette Delaloge, head of the cancer prevention program at France's Gustave Roussy institute, was also not involved in the research but discussed it with AFP in Paris this weekend.
"The study is quite an important step for science—and for society too, I hope," she said, noting that it was "quite revolutionary, because we had practically no prior demonstration of this alternative way of cancer forming."
"This opens a huge door, both for knowledge but also for new ways to prevent" cancer, added Delaloge. "This level of demonstration must force authorities to act on an international scale."
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Fossil fuel air pollution already causes 91,000 premature U.S. deaths each year, according to a recent study.
A new Princeton-led study finds that ambitious climate policies could prevent 6,000 deaths annually by 2030.
Cities like New York, London, and Mexico City show that low-emission zones and congestion charges improve air quality and public health.
Recent studies have shown the severe health effects of air pollution on human health, with fossil fuel air pollution alone linked to 91,000 U.S. deaths every year. Now, another study shows how cutting U.S. air pollution could save as many as 6,000 lives a year by 2030. Some cities around the globe have already introduced measures to cut air pollution, while air pollution in other areas continues to worsen, with a significant knock-on effect on human health.
Air pollution from oil and gas causes as many as 91,000 premature U.S. deaths a year, according to a study published in Science Advances in August. Meanwhile, the United States Trump administration is working to water down regulations protecting communities across the country from the worst sources of air pollution, much to the dismay of climate scientists and health experts worldwide.
Now, a recently published study suggests that the efforts being taken to tackle climate change could help reduce the number of deaths caused by air pollution by around 6,000 annually by the end of the decade. The study, led by Princeton University and published in One Earth, says that the growing and ageing population is more vulnerable to the impacts of air pollution and that the deaths linked to this form of pollution are likely to increase unless action is taken.
The study assesses pollution sources and population, exploring the health gains from climate action across each U.S. state and most counties. It revealed that reducing fossil fuel combustion results in an almost immediate reduction in air pollution.
The study’s lead author, Xinyuan Huang, stated, “Climate actions not only reduce carbon emissions but also bring significant air-quality improvements to regions with historically high pollution levels.” Huang added, “Under ambitious climate policies, states like West Virginia and Kentucky could see deaths from particle pollution decrease by over 19 percent in 2030, demonstrating the substantial health benefits of shifting away from fossil fuels.”
Some of the actions that could help reduce air pollution include the accelerated rollout of renewable energy projects, the replacement of gas boilers in buildings with heat pumps, an increase in the uptake of electric vehicles and the electrification of passenger transport and freight. The study suggested that some of these changes may be encouraged by the introduction of low- and zero-emission zones and decongestion charging schemes that have already been introduced in cities such as New York, London, and Mexico City.
In New York, the government introduced a $9 congestion toll in January to deter people from driving in the city and encourage more people to use public transport. The fees will contribute towards improvements to the city’s severely underfunded public transit system. New York lawmakers have been proposing the congestion zone charge in New York’s busiest areas for decades, since 1952 in fact, but it was first proposed to the state government and rejected in 2007. State legislators have long criticised the fee, saying it would have the greatest impact on blue-collar workers and that it should not be used to fix the mismanagement of public transport funding by the Metropolitan Transportation Authority. Some also warned of congestion in outer-borough streets in response to the charge.
However, the new charge was finally granted approval by the federal government in 2023, although implementation was paused in June 2024, and the fee was eventually rolled out at a reduced rate of $9 in January, rather than the planned $15. The initial results from the charge have been positive, with public transit ridership reaching its highest level since the pandemic and anticipated annual revenues from the toll of $500 million.
In the U.K., London has had a congestion and low-emissions charge in place for several years, which has encouraged greater passenger transport uptake and has decreased traffic in the centre of the city. In August 2023, the Mayor of London expanded the Ultra Low Emission Zone (ULEZ) across all London boroughs – covering nine million people – to tackle climate pollution. In the first year of the scheme, the mayor’s office found that ULEZ helped reduce the number of older, more-polluting vehicles seen driving in London and has reduced the levels of harmful air pollution that Londoners are exposed to.
Similar efforts have been seen in Mexico City, which once had one of the highest levels of air pollution in the world. The Hoy No Circula initiative was first introduced in 1989, and the most recent version was launched in 2014, as part of the city’s Comprehensive Program Against Atmospheric Pollution (PICCA), to restrict the use of private vehicles on specific days, thereby reducing vehicle emissions that harm health. Since the launch of the initiative, Mexico City has experienced a significant improvement in air quality.
With more studies showing the clear link between air pollution and premature deaths, it is vital that governments do more to reduce the level of harmful emissions linked to various health conditions. The introduction of schemes such as low-emission zones and congestion charges across major cities worldwide has been shown to improve air quality and encourage healthy habits, such as the wider use of public transport. Meanwhile, greater reductions in the burning of fossil fuels could further reduce air pollution beyond urban areas.
By Felicity Bradstock for Oilprice.com
Ethnicity and social class affect lung cancer survival rates
People from different backgrounds interacting in London. Image by Tim Sandle.
The most comprehensive study yet conducted of lung cancer diagnosis in England has revealed significant disparities between ethnic groups and striking evidence that people living in the most deprived areas were diagnosed with lung cancer at twice the rate of those in affluent areas.
The study, published in the journal The Lancet Regional Health – Europe, which is the largest of its kind, analysed health records of over 17.5 million people and more than 84,000 lung cancer cases, found that Bangladeshi men had the highest rates of lung cancer, while people from the most deprived areas developed the disease at twice the rate of those from affluent areas.
Among those who developed lung cancer, people from deprived areas had a 35% higher risk of being diagnosed with more aggressive forms of the disease.
Researchers from Oxford’s Nuffield Department of Primary Care Health Sciences found clear evidence that different ethnic groups show distinct patterns of lung cancer types, with important implications for screening and early detection.
Professor Julia Hippisley-Cox, senior author of the study, states: “This research provides the strongest evidence yet of how your ethnic background and social circumstances affect both your risk of developing lung cancer and the type of cancer you may develop. These findings are particularly timely as the NHS rolls out its targeted lung cancer screening programme.”
Key findingsBangladeshi men showed the highest lung cancer rates, followed by White, Chinese and Caribbean men Women and people from Indian, Caribbean, Black African, Chinese and other Asian backgrounds were twice as likely to be diagnosed with adenocarcinoma, one of the most common types of lung cancer
Lung cancer occurred twice as frequently in the most deprived areas compared to the least deprived areas (215 vs 94 cases per 100,000 person-years for men; 147 vs 62 for women)
Men and current smokers were more likely to be diagnosed at later stages of cancer than women and non-smokers
These data show clear patterns in how lung cancer affects different communities across England. This infers that ethnic background and social circumstances play crucial roles in both cancer risk and how the disease develops.
The findings come in the context of the UK NHS rolling out its Targeted Lung Health Check Programme across England. This screening initiative currently focuses on areas with high lung cancer rates and social deprivation, aiming to detect cancer earlier when it’s more treatable. The new research could help ensure these vital health checks reach those most at risk and are tailored to different community needs.
Early detection through targeted screening could significantly reduce treatment costs for the NHS, as late-stage cancer care is considerably more expensive. More importantly, catching cancer earlier could save thousands of lives each year.
The research highlights how social factors like poverty and healthcare access affect cancer outcomes.
To address this, cancer services need to reach out to all communities effectively so that everyone has the same opportunity for early diagnosis, regardless of their background or where they live.
This needs to go hand-in-hand with policies that address fundamental inequalities in healthcare access and to reduce social deprivation.
Saturday, September 10, 2022
Scientists discover how air pollution may trigger lung cancer in never-smokers
Particles linked to climate change also promote cancerous changes in airway cells
Cells with EGFR and KRAS gene mutations can turn cancerous when exposed to air pollutants
Late-breaking data pave way to new approaches to lung cancer prevention and treatment
Paris, France, 10 September 2022 - A new mechanism has been identified through which very small pollutant particles in the air may trigger lung cancer in people who have never smoked, paving the way to new prevention approaches and development of therapies, according to late-breaking data [to be] reported at the ESMO Congress 2022 by scientists of the Francis Crick Institute and University College London, funded by Cancer Research UK (1). The particles, which are typically found in vehicle exhaust and smoke from fossil fuels, are associated with non-small cell lung cancer (NSCLC) risk, accounting for over 250,000 lung cancer deaths globally per year (2,3).
“The same particles in the air that derive from the combustion of fossil fuels, exacerbating climate change, are directly impacting human health via an important and previously overlooked cancer-causing mechanism in lung cells. The risk of lung cancer from air pollution is lower than from smoking, but we have no control over what we all breathe. Globally, more people are exposed to unsafe levels of air pollution than to toxic chemicals in cigarette smoke, and these new data link the importance of addressing climate health to improving human health,” said Charles Swanton, the Francis Crick Institute and Cancer Research UK Chief Clinician, London, UK, who will present the research results at the ESMO 2022 Presidential Symposium on Saturday, 10 September.
The new findings are based on human and laboratory research on mutations in a gene called EGFR which are seen in about half of people with lung cancer who have never smoked. In a study of nearly half a million people living in England, South Korea and Taiwan, exposure to increasing concentrations of airborne particulate matter (PM) 2.5 micrometres (μm) in diameter was linked to increased risk of NSCLC with EGFR mutations.
In the laboratory studies, the Francis Crick Institute scientists showed that the same pollutant particles (PM2.5) promoted rapid changes in airway cells which had mutations in EGFR and in another gene linked to lung cancer called KRAS, driving them towards a cancer stem cell like state. They also found that air pollution drives the influx of macrophages which release the inflammatory mediator, interleukin-1β, driving the expansion of cells with the EGFR mutations in response to exposure to PM2.5, and that blockade of interleukin-1β inhibited lung cancer initiation. These findings were consistent with data from a previous large clinical trial showing a dose dependent reduction in lung cancer incidence when people were treated with the anti-IL1β antibody, canakinumab (4).
In a final series of experiments, the Francis Crick team used state-of-the-art, ultradeep mutational profiling of small samples of normal lung tissue and found EGFR and KRAS driver mutations in 18% and 33% of normal lung samples, respectively.
“We found that driver mutations in EGFR and KRAS genes, commonly found in lung cancers, are actually present in normal lung tissue and are a likely consequence of ageing. In our research, these mutations alone only weakly potentiated cancer in laboratory models. However, when lung cells with these mutations were exposed to air pollutants, we saw more cancers and these occurred more quickly than when lung cells with these mutations were not exposed to pollutants, suggesting that air pollution promotes the initiation of lung cancer in cells harbouring driver gene mutations. The next step is to discover why some lung cells with mutations become cancerous when exposed to pollutants while others don’t,” said Swanton.
Commenting on the results, Tony Mok, Chinese University of Hong Kong, not involved in the study, said: “This research is intriguing and exciting as it means that we can ask whether, in the future, it will be possible to use lung scans to look for pre-cancerous lesions in the lungs and try to reverse them with medicines such as interleukin-1β inhibitors. We don’t yet know whether it will be possible to use highly sensitive EGFR profiling on blood or other samples to find non-smokers who are predisposed to lung cancer and may benefit from lung scanning, so discussions are still very speculative.”
Like Swanton, he stresses the importance of reducing air pollution to lower the risk of lung diseases, including cancer. “We have known about the link between pollution and lung cancer for a long time, and we now have a possible explanation for it. As consumption of fossil fuels goes hand in hand with pollution and carbon emissions, we have a strong mandate for tackling these issues – for both environmental and health reasons,” Mok concluded.
-END-
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Notes to Editors Please make sure to use the official name of the meeting in your reports: ESMO Congress 2022 Official Congress Hashtag: #ESMO22
Disclaimer This press release contains information provided by the author of the highlighted abstract and reflects the content of this abstract. It does not necessarily reflect the views or opinions of ESMO who cannot be held responsible for the accuracy of the data. Commentators quoted in the press release are required to comply with the ESMO Declaration of Interests policy and the ESMO Code of Conduct.
References
1 LBA1 ‘Mechanism of action and an actionable inflammatory axis for air pollution induced non-small cell lung cancer in never smokers’ will be presented by Charles Swanton during Presidential Symposium 1 on Saturday, 10 September, 16:30 to 18:00 CEST in Paris Auditorium. Annals of Oncology, Volume 33 Supplement 7, September 2022
2 Liu X, Mubarik S, Wang S. Lung Cancer Death Attributable to Long-Term Ambient Particulate Matter (PM2.5) Exposure in East Asian Countries During 1990–2019. Frontiers in Medicine 2021 Oct 15;8:742076
3 Turner MC, Andersen ZJ, Baccarelli A et al. Outdoor Air Pollution and Cancer: An Overview of the Current Evidence and Public Health Recommendations. CA: Cancer J Clin 2020; 70: 460-479
4 Ridker PM, MacFadyen JG, Thuren T et al. Effect of interleukin-1β inhibition with canakinumab on incident lung cancer in patients with atherosclerosis: exploratory results from a randomised, double-blind, placebo-controlled trial. Lancet 2017 Oct 21; 390 (10105): 1833-1842
ESMO is the leading professional organisation for medical oncology. With 25,000 members representing oncology professionals from over 160 countries worldwide, ESMO is the society of reference for oncology education and information. Drawing on more than 45 years of experience, ESMO serves its members and the oncology community by providing networking and professional growth opportunities: oncologists can engage in projects, committees and working groups aiming to promote science and foster improvements in the oncology practice. With training, resources and tools, oncologists are enabled to stay up to date with the latest scientific advances and continue to deliver the best possible care to cancer patients. By representing and advocating for the oncology community at the highest political levels, ESMO ensures that the needs of both patients and doctors are properly taken care of. Driven by a shared determination to secure the best possible outcomes for patients, ESMO is committed to standing by those who care about cancer through addressing the diverse needs of #ONEoncologycommunity, offering #educationforLIFE, and advocating for #accessiblecancerCARE. www.esmo.org
The Francis Crick Institute is a biomedical discovery institute dedicated to understanding the fundamental biology underlying health and disease. Its work is helping to understand why disease develops and to translate discoveries into new ways to prevent, diagnose and treat illnesses such as cancer, heart disease, stroke, infections, and neurodegenerative diseases. An independent organisation, its founding partners are the Medical Research Council (MRC), Cancer Research UK, Wellcome, UCL (University College London), Imperial College London and King’s College London. The Crick was formed in 2015, and in 2016 it moved into a brand new state-of-the-art building in central London which brings together 1500 scientists and support staff working collaboratively across disciplines, making it the biggest biomedical research facility under a single roof in Europe. www.crick.ac.uk
Cancer Research UK is the world’s leading cancer charity dedicated to saving lives through research, influence and information. Cancer Research UK’s pioneering work into the prevention, diagnosis and treatment of cancer has helped save millions of lives. Cancer Research UK has been at the heart of the progress that has already seen survival in the UK double in the last 40 years. Today, 2 in 4 people survive their cancer for at least 10 years. Cancer Research UK wants to accelerate progress and see 3 in 4 people surviving their cancer by 2034. Cancer Research UK supports research into the prevention and treatment of cancer through the work of over 4,000 scientists, doctors and nurses. Together with its partners and supporters, Cancer Research UK is working towards a world where people can live longer, better lives, free from the fear of cancer. www.cancerresearchuk.org or +44(0) 300 123 1022
LBA1 - Mechanism of action and an actionable inflammatory axis for air pollution induced non-small cell lung cancer: towards molecular cancer prevention
C. Swanton1, W. Hill2, E. Lim3, C. Lee4, C.E. Weeden5, M. Augustine6, K. Chen7, F.-C. Kuan8, F. Marongiu9, F. Rodrigues10, H. Cha11, T. Jacks12, M. Luchtenborg13, I. Malanchi14, J. Downward15, C. Carlsten16, A. Hackshaw17, K.R. Litchfield18, J. DeGregori19, M. Jamal-Hanjani20
1Translational Cancer Therapeutics Department, Francis Crick Institute, London/United Kingdom, 2Cancer Evolution And Genome Instability Laboratory, Francis Crick Institute, London/United Kingdom, 3Cancer Evolution And Genome Instability Laboratory, The Francis Crick Institute, London/United Kingdom, 4Cegi, Francis Crick Institute, London/United Kingdom, 51 Midland Rd, The Francis Crick Institute, London/United Kingdom, 6Tumour Immunogenomics And Immunosurveillance, UCL - University College London, London/United Kingdom, 7Thoracic Surgery, Peking University People’s Hospital, Beijing/China, 8Hematology Oncology, Chang Gung Medical Foundation - Chiayi Chang Gung Memorial Hospital, Puzi City/Taiwan, 9Department Of Biochemistry & Molecular Genetics, UCHealth Cancer Care - Anschutz Medical Campus - University of Colorado Cancer Center, Aurora/United States of America, 10Tumour-host Interaction Laboratory, The Francis Crick Institute, London/United Kingdom, 11Division Of Hematology-oncology, Samsung Medical Center (SMC) - Sungkyunkwan University School of Medicine, Seoul/Korea, Republic of, 12The Jacks Lab, Koch Institute For Integrative Cancer Research at MIT, Cambridge/United States of America, 13National Cancer Registration And Analysis Service, Public Health England, London/United Kingdom, 14Tumour Host Interaction Lab, Francis Crick Institute, London/United Kingdom, 15Oncogene Biology Laboratory, The Francis Crick Institute, London/United Kingdom, 16Centre For Lung Health, UBC - The University of British Columbia, Vancouver/Canada, 17Clinical Trials, Cancer Research UK & University College London Cancer Trials Centre, London/United Kingdom, 18Tumour Immunogenomics And Immunosurveillance, UCL Cancer Institute - UCL - London's Global University, London/United Kingdom, 19Biochemistry And Molecular Genetics, UCHealth Cancer Care - Anschutz Medical Campus - University of Colorado Cancer Center, Aurora/United States of America, 20Medical Oncology Dept., UCL Cancer Institute - Paul O'Gorman Building, London/United Kingdom
Background: A mechanistic basis for non-small cell lung cancer (NSCLC) initiation in never smokers, a disease with a high frequency of EGFR mutations (EGFRm), is unknown. The air pollutant, particulate matter (PM), is known to be associated with the risk of NSCLC, however a direct cause and mechanism remain elusive.
Methods: We analysed 463,679 individuals to address the associations of increasing 2.5um PM (PM2.5) concentrations with cancer risk. We performed ultra-deep profiling of 247 normal lung tissue samples, analysed normal lung tissue from humans and mice following exposures to PM, and investigated the consequences of PM on tumour promotion in mouse lung cancer models.
Results: Increasing PM2.5 levels were associated with increased risk of EGFRm NSCLC in England, S.Korea and Taiwan and with increased risk of mesothelioma (HR=1.19), lung (HR=1.16), anal (HR=1.23), small intestine (HR=1.30), GBM (HR=1.19), lip, oral cavity and pharynx (HR: 1.15) and laryngeal carcinomas (HR=1.26) in UK Biobank; HR for each 1ug/m3 PM2.5 increment. 18-33% of normal lung tissue samples harbour driver mutations in EGFR and KRAS in the absence of malignancy. PM promotes a macrophage response and a progenitor-like state in lung epithelium harbouring mutant EGFR. Consistent with PM promoting NSCLC in at-risk epithelium harbouring driver mutations, PM increased tumour burden in three EGFR or KRAS driven lung cancer models in a dose-dependent manner. Finally, we uncover an actionable inflammatory axis driven by IL1B in response to PM, with anti-IL1B therapy preventing PM-induced mouse tumour formation, consistent with reductions in human lung cancer incidence with anti-IL1B therapy.
Conclusions: These results shed light on the aetiology of EGFRm lung cancer, particularly in never-smokers, and suggest that oncogenic mutations may be necessary but insufficient for tumour formation. These data reveal a mechanistic basis for PM driven lung cancer in the absence of classical carcinogen-driven mutagenesis, reminiscent of models of tumour initiation and promotion proposed 70 years ago, providing evidence to limit air pollution and opportunities for molecular targeted cancer prevention.
Clinical trial identification: TRAcking Non-small Cell Lung Cancer Evolution Through Therapy (Rx) (TRACERx) (NCT01888601) The PEACE (Posthumous Evaluation of Advanced Cancer Environment) Study (PEACE) (NCT03004755) Biomarkers and Dysplastic Respiratory Epithelium (NCT00900419)
Legal entity responsible for the study: Francis Crick Institute and UCL Hospitals NHS Trust
Funding: Foundation or academic group WITHOUT funding from a pharma, biotech, or other commercial company - This work has been supported by the Mark Foundation ASPIRE I Award (Grant 21-029-ASP), Lung Cancer Research Foundation Grant on Disparities in Lung Cancer, Advanced Grant (PROTEUS, Grant Agreement no. 835297), CRUK EDD (EDDPMA-Nov21100034), and Rosetrees Out-of-round Award (OoR2020100009). E.L.L. receives funding from NovoNordisk Foundation (ID 16584), The Mark Foundation (Grant 21-029-ASP) and has been supported by Rosetrees. W.H is funded by an ERC Advanced Grant (PROTEUS, Grant Agreement no. 835297), CRUK EDD (EDDPMA-Nov21100034), The Mark Foundation (Grant 21-029-ASP) and has been supported by Rosetrees. K.C. is supported by Research Unit of Intelligence Diagnosis and Treatment in Early Non-small Cell Lung Cancer, Chinese Academy of Medical Sciences (2021RU002), National Natural Science Foundation of China (No.82072566) and Peking University People's Hospital Research and Development Funds (RS2019-01). T.K. receives grant support from JSPS Overseas Research Fellowships Program (202060447). S.H.L is supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No. 2020R1A2C3006535), the National Cancer Center Grant (NCC1911269-3), and a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number : HR20C0025). N.M. is a Sir Henry Dale Fellow, jointly funded by the Wellcome Trust and the Royal Society (Grant Number 211179/Z/18/Z) and also receives funding from Cancer Research UK, Rosetrees and the NIHR BRC at University College London Hospitals and the CRUK University College London Experimental Cancer Medicine Centre. J.D., M.G., Y.E.M. D.T.M. and R.L.K receive funding from American Association for Cancer Research/Johnson&Johnson (18-90-52-DEGR), and J.D. is supported by the Courtenay C. and Lucy Patten Davis Endowed Chair in Lung Cancer Research. M.G., Y.E.M. D.T.M. and R.L.K. were supported by National Cancer Institute (NCI) RO1 CA219893. E.J.E. was supported by NCI Ruth L. Kirschstein National Research Service Award T32-CA190216. The work at the University of Colorado was also supported by NCI Cancer Center Support Grant P30CA046934. M.J.-H. has received funding from Cancer Research UK, National Institute for Health Research, Rosetrees Trust, UKI NETs and NIHR University College London Hospitals Biomedical Research Centre. C.S. is Royal Society Napier Research Professor. He is supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK (FC001169), the UK Medical Research Council (FC001169), and the Wellcome Trust (FC001169). C.S. is funded by Cancer Research UK (TRACERx, PEACE and CRUK Cancer Immunotherapy Catalyst Network), Cancer Research UK Lung Cancer Centre of Excellence, the Rosetrees Trust, Butterfield and Stoneygate Trusts, NovoNordisk Foundation (ID16584), Royal Society Research Professorships Enhancement Award (RP/EA/180007), the NIHR BRC at University College London Hospitals, the CRUK-UCL Centre, Experimental Cancer Medicine Centre and the Breast Cancer Research Foundation (BCRF). This research is supported by a Stand Up To Cancer-LUNGevity-American Lung Association Lung Cancer Interception Dream Team Translational Research Grant (SU2C-AACR-DT23-17). Stand Up To Cancer is a program of the Entertainment Industry Foundation. Research grants are administered by the American Association for Cancer Research, the Scientific Partner of SU2C. C.S. also receives funding from the European Research Council (ERC) under the European Union’s Seventh Framework Programme (FP7/2007-2013) Consolidator Grant (FP7-THESEUS-617844), European Commission ITN (FP7-PloidyNet 607722), an ERC Advanced Grant (PROTEUS) from the European Research Council under the European Union’s Horizon 2020 research and innovation programme (835297) and Chromavision from the European Union’s Horizon 2020 research and innovation programme (665233). This work was supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK (grant no. FC001112), the UK Medical Research Council (grant no. FC001112), and the Wellcome Trust (grant no. FC001112) and the European Research Council (grant no. ERC CoG-H2020-725492).
Disclosure:C. Swanton: Financial Interests, Personal, Invited Speaker, Activity took place in 2016.: Pfizer; Financial Interests, Personal, Invited Speaker, October 26th 2020: Novartis; Financial Interests, Personal, Invited Speaker: Roche/Ventana; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Invited Speaker, Activity took place in 2016.: Celgene; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Illumina; Financial Interests, Personal, Advisory Board, AdBoard - November 12th, 2020: Amgen; Financial Interests, Personal, Advisory Board: Genentech; Financial Interests, Personal, Advisory Board: Sarah Canon Research Institute; Financial Interests, Personal, Advisory Board, Joined October 2020. Also have stock options: Bicycle Therapeutics; Financial Interests, Personal, Advisory Board: Medicxi; Financial Interests, Personal, Invited Speaker: GlaxoSmithKline; Financial Interests, Personal, Advisory Board, Member of the Science Management Committee. Also have stock options: GRAIL; Financial Interests, Personal, Other, Consultancy agreement: Roche Innovation Centre Shanghai; Financial Interests, Personal, Full or part-time Employment, Chief Clinician since October 2017: Cancer Research UK; Financial Interests, Personal, Ownership Interest, Co-Founder of Achilles Therapeutics. Also, have stock options in this company.: Achilles Therapeutics; Financial Interests, Personal, Stocks/Shares, Stocks owned until June 2021: GRAIL; Financial Interests, Personal, Stocks/Shares, Stocks owned until June 2021: Apogen Biotechnologies; Financial Interests, Personal, Stocks/Shares: Epic Biosciences; Financial Interests, Personal, Stocks/Shares: Bicycle Therapeutics; Financial Interests, Institutional, Research Grant, Funded RUBICON grant - October 2018 - April 2021.: Bristol Myers Squibb; Financial Interests, Institutional, Research Grant, Collaboration in minimal residual disease sequencing technologies.: Archer Dx Inc; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Invited Speaker, Chief Investigator for the MeRmaiD1 clinical trial and chair of the steering committee.: AstraZeneca; Financial Interests, Institutional, Research Grant: Ono Pharmaceutical; Financial Interests, Institutional, Research Grant: Boehringer Ingelheim; Financial Interests, Institutional, Research Grant, Research Grants from 2015-2019.: Roche-Ventana; Financial Interests, Personal, Other, Co-chief investigator: NHS-Galleri Clinical Trial; Non-Financial Interests, , Principal Investigator, Chief Investigator for MeRmaiD1 clinical trial: AstraZeneca; Non-Financial Interests, , Invited Speaker, From 2019: AACR; Non-Financial Interests, , Other, Board of Directors: AACR; Non-Financial Interests, , Advisory Role, EACR Advisory Council member: EACR. T. Jacks: Financial Interests, Personal, Member of the Board of Directors: Amgen; Financial Interests, Personal, Member of the Board of Directors: Thermo Fisher Scientific; Financial Interests, Personal, Advisory Board, co-Founder: Dragonfly Therapeutics; Financial Interests, Personal, Other, co-Founder: T2 Biosystems; Financial Interests, Personal, Advisory Board: SQZ Biotech; Financial Interests, Personal, Advisory Board: Skyhawk Therapeutics; Financial Interests, Personal, Leadership Role: Break Through Cancer; Financial Interests, Institutional, Funding: Johnson & Johnson. J. Downward: Financial Interests, Personal, Other, consultant: AstraZeneca; Financial Interests, Personal, Other, consultant: Bayer; Financial Interests, Personal, Other, consultant: Jubilant; Financial Interests, Personal, Other, consultant: Theras; Financial Interests, Personal, Other, consultant: Vividion; Financial Interests, Personal, Other, consultant: Novartis; Financial Interests, Institutional, Research Grant: BMS; Financial Interests, Institutional, Research Grant: Revolution Medicines; Financial Interests, Institutional, Research Grant: Boehringer Ingelheim. K.R. Litchfield: Financial Interests, Personal, Invited Speaker: Roche Tissue Diagnostics; Financial Interests, Personal, Other, Consulting work: Monopteros Therapeutics; Financial Interests, Institutional, Research Grant: Ono/LifeArc; Financial Interests, Institutional, Research Grant, Research funding: Genesis Therapeutics; Non-Financial Interests, Institutional, Proprietary Information, Collaboration on data analysis: Bms. M. Jamal-Hanjani: Financial Interests, Personal, Invited Speaker, Invited speaker honorarium: Oslo Cancer Cluster; Financial Interests, Personal, Invited Speaker, Invited speaker honorarium: Astex Pharmaceutical; Non-Financial Interests, , Advisory Role, Scientific Advisory Board and Steering Committee member: Achilles Therapeutics; Other, , Other, I am named as co-inventor on patent PCT/US2017/028013 relating to methods for lung cancer detection.: Patent. All other authors have declared no conflicts of interest.
Late-breaking results presented at the ESMO Congress 2022 elucidate the link between air pollution and lung cancer
ESMO partners with EONS to launch the Cancer Prevention across Europe (PrEvCan) campaign
Study confirms accuracy of multi-cancer early detection blood testing, paving the way for a new era in cancer screening
Paris, France, 9 September 2022 – Sustainability will be at the heart of many discussions at the ESMO Congress 2022, as illustrated by the new results and initiatives spanning cancer prevention, early detection and treatment that were announced today during the opening press conference to the annual meeting of the international oncology community taking place 9-13 September in Paris, France.
“By definition, sustainability is about being able to maintain important, high-quality processes over time. In oncology, seeing the rise in cancer cases, we need to ask ourselves how we can make sure the essential process of caring for patients can be maintained,” said ESMO President Prof. Solange Peters. “Sustainability encompasses the notion of avoiding degradation, meaning that we also have to look at maintaining the quality – which, in cancer, includes the availability of and access to anticancer drugs. It also includes quality of life, which is still dependent on the environment, and as ESMO we need to start looking at the environmental sustainability of everything we do.”
Underscoring the multifaceted nature of sustainability as a societal goal, late-breaking results to be presented at the ESMO Congress 2022 offer a deeper understanding of the long-established link between air pollution and non-small cell lung cancer (NSCLC) arising in people who have never smoked, and make clear the link between climate change and human health. “Pollution has a known association with lung cancer, but we didn’t know if and how it directly causes the disease,” said study author and ESMO 2022 Scientific Co-Chair Prof. Charles Swanton, the Francis Crick Institute and Cancer Research UK Chief Clinician, London, UK, explaining the background to this work. (1)
The research, based on human and laboratory studies, showed for a population of nearly half a million people living in England, South Korea and Taiwan that exposure to increasing concentrations of airborne particulate matter (PM) 2.5 micrometres (μm) in diameter was linked to increased risk of NSCLC with mutations in the EGFR gene, which are known to be present in about half of people with lung cancer who have never smoked. In laboratory mouse models, the same pollutant particles (PM2.5) were seen to directly cause lung cancer by acting through lung tissue inflammation, driving the release of a molecule known as interleukin-1β that causes epithelial cells to transdifferentiate into cancer stem-like cells. In the presence of mutations in EGFR and in another gene linked to lung cancer called KRAS, these cells can then bloom into a tumour.
“These mutations can be found in over half of normal lung tissue biopsies and are a natural process of ageing. They are necessary, but not sufficient to drive cancer: it is in combination with pollution that the cancer stem cells can expand and initiate a tumour. This begins to explain how environmental carcinogens that don’t induce DNA mutations can drive cancer,” said Swanton, deriving from this discovery a public health mandate to lower the levels of these pollutants, which are produced by the combustion of fossil fuels. “We have to achieve a 50% reduction in greenhouse gas emissions by 2030, and by doing so we will naturally reduce levels of PM2.5. We can all play a part here: we need to cycle more, walk more. It’s worth bearing in mind that PM2.5 cause 8 million deaths a year, not just due to cancer but also to other diseases like cardiovascular disease, strokes, dementia – that is more than the deaths caused by tobacco globally.”
In light of the fact that his research confirmed the blockade of interleukin-1β could inhibit lung cancer initiation by blocking the pollution-induced transformation of airway cells into cancer stem cells, Swanton also suggested that targeting interleukin-1β should be further explored in the future as a potential new approach to cancer prevention.
The findings come in a context where the global incidence of respiratory cancers is on the rise, with annual new cases expected to jump by about 70% over the next two decades. In Europe alone, similar trends observed for other malignancies could result in an increase in overall cancer mortality, from 2 million annual deaths in 2020, to as many as 3 million by 2040. (2) As up to half of all cancers are thought to be preventable, prevention is considered by the World Health Organisation to be the most cost-effective, and thus the most sustainable, long-term strategy for cancer control.
“The ESMO Vision 2025, made very clear that if we want to succeed in tackling cancer, we need to develop a clear plan for primary and secondary prevention, continue to offer the optimal care for cancers that cannot be prevented and adequately support cancer survivorship. Focusing on only one of these areas and neglecting the others would lead to failure,” said ESMO Director of Public Policy Dr. Rosa Giuliani.
In line with the Society’s commitment to promoting research-based cancer prevention, the ESMO representatives joined European Oncology Nursing Society (EONS) Executive Board member Dr. Lena Sharp, Regional Cancer Centre, Stockholm, Sweden, in announcing the launch today of the Cancer Prevention across Europe Campaign (PrEvCan).
Led by EONS with ESMO as key partner alongside other international organisations, the campaign will over a one-year period dedicate each month to promoting and explaining the scientific evidence for each one of the 12 recommendations of the European Code Against Cancer (ECAC) to prevent the disease, starting in October with smoking as one of the most important cancer risk factors.
“What is new here is that it is the cancer care workforce leading the way,” said Sharp, the PrEvCan project leader. “We are the ones who meet patients and their families, so we could intervene on a daily basis supporting and advising people to adopt healthier lifestyles to reduce the risk of new cancers but also to reduce negative effects on the current disease.”
The campaign will target the general public, including the most vulnerable groups who can be difficult to reach with health promotion and lifestyle advice, but equally healthcare professionals, who according to Sharp can also take a more prominent role in supporting vaccination and screening programmes.
The ESMO President added: “We thought for a while that prevention should be in the hands of family doctors, but then we started to learn that preventing the disease must be at least partly in the hands of the specialists of a specific disease, in order to convince people about its importance. Particularly after COVID, a certain degree of suspicion can happen in medicine. You need to make sure that everything you propose has a basis – and one of these bases for cancer prevention is the burden of cancer, what it represents not only in terms of lost years of life but also in terms of the sustainability of our societies and healthcare systems.” Peters further highlighted that oncologists should view prevention as an integral part of oncology care, also because the science of prevention still requires more data.
For cancers that are not currently avoidable, screening and early detection has the potential to both maximise individuals’ chances of survival, and alleviate the burden on health systems by reducing the proportion of patients with advanced disease who require costly, chronic therapies and care.
A study to be presented at this year’s Congress could lead to a major paradigm shift in this field, having confirmed the feasibility of multi-cancer early detection (MCED) blood testing as a method of screening for up to 50 different cancer types simultaneously. (3)
“This is one of the very first studies where the detection of cancer DNA in the blood has allowed us to detect cancer at an early stage,” said ESMO 2022 Scientific Co-Chair Prof. Fabrice André, Institute Gustave Roussy, Villejuif, France. “If this test works, in the future, it will be good news for patients, but most cancer centres are not equipped to scale up surgeries for hundreds more patients with, say, early-stage pancreatic cancer. With this landmark study comes a need for a wake-up call for hospitals to see what will happen in 10 years and start now to train fellows and change their infrastructures accordingly.”
Highlighting the time and patience required to turn promising research results into meaningful innovation for patients, Swanton observed: “ESMO 2022 is a celebration of the collaboration between basic scientists and healthcare professionals to advance care for our patients. Some of the breakthroughs that will be discussed over the next four days have come from biological studies of worms, yeast, bacteria and plants – but they took 30 or 40 years of painstaking science from the bench to the bedside. We need our funders to recognise that and to sustain investment in discovery research to generate the medicines of the future.”
Among other highly anticipated results to be presented at the ESMO Congress 2022 , André drew attention to several examples of novel approaches which could soon become a reality in the clinic: from the phase III trial of gamma secretase inhibitor (GSI) nirogacestat, a first-in-class drug targeting a new molecular alteration in a rare category of cancers known as desmoid tumours, through a landmark trial of cell therapy using tumour-infiltrating lymphocytes (TILs) to improve the outcomes of patients with advanced melanoma, all the way to several late-phase trials of immunotherapy, including for non-small cell lunger cancer patients not eligible to standard platinum chemotherapy. André welcomed the presence of studies for underrepresented patient populations in the Congress’s scientific programme, concluding: “We cannot exclude patients from clinical trials.”
In closing, ESMO 2022 Press Officer Dr. Antonio Passaro called for a wide and wise dissemination of the data to be presented: “We have here a community of about 25,000 people, with more than 1,900 abstracts and 76 LBAs that will be presented in the coming days. We need to pass these messages to all of our colleagues and the public in order to dramatically improve the future of our patients, which risks being worse than it is today considering current cancer incidence trends.”
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Notes to Editors
Please make sure to use the official name of the meeting in your reports: ESMO Congress 2022
3 Abstract 903O ‘A prospective study of a multi-cancer early detection blood test’ will be presented by Deb Schrag during the proffered paper
session “Basic science and translational research” on Sunday, 11 September, 16:30 to 18:00 CEST in Orléans Auditorium. Annals of Oncology,
Volume 33 Supplement 7, September 2022
4 The ESMO ANMS 2.0 survey about access to cancer medicines will be discussed during the educational session “The Universal Health Coverage (UHC) dilemma: Can we afford to pay for what we want?” on Saturday, 10 September, 8:30 to 10:00 CEST in Marseille Auditorium.
ESMO is the leading professional organisation for medical oncology. With 25,000 members representing oncology professionals from over 160 countries worldwide, ESMO is the society of reference for oncology education and information. Driven by a shared determination to secure the best possible outcomes for patients, ESMO is committed to standing by those who care about cancer through addressing the diverse needs of #ONEoncologycommunity, offering #educationforLIFE, and advocating for #accessiblecancerCARE. www.esmo.org
