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Outdoor Air Pollution and Lung Cancer

Joan Schiller, MD

Oncology Advocates United for Climate and Health – International

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Air pollution from fossil fuels caused 8.7 million premature deaths in 2018

Vohra, Environmental Research, 195: 2021

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Lung Cancer Deaths due to Air Pollution - 2017�

265,267 deaths globally

14% of all lung cancer deaths worldwide

Turner, C. CA CANCER J CLIN 2020; 70:460–4

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Air Pollution, Climate Change, and Cancer

Direct Effects

Causes:

Lung cancer
Probably:

Breast cancer
Brain cancer
Bladder

Consequences of climate change

Access to care -> Affects prognosis and treatment outcomes

Delays in screening
Delays in treatment
Delays in research
Impacts the pharmacokinetics of many cancer drugs

What is the connection between air pollution and cancer? The most direct effect of air pollution is that it causes lung cancer. This is incontrovertible, as I’ll show you. There is emerging evidence that it causes other cancers as well – eg breast, brain, bladder

We won’t have time today to discuss some of the other consequences of climate change, which are also very important. And that is, as you know climate change causes severe weather events, which delays access to care, delays in screening, delays in treatment, delays in research, all of which impact prognosis and cancer outcomes. And heat can impact how we metabolize many of our drugs, such as by causing diarhea and putting vulnerable patient at risk for dehydration. Some of our cancer drugs cause sun sensitivity and some can be degraded or damaged by the heat. some medications for those who have, can impact the pharmokinetics of some of our drugs.,

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Air Pollution

Classified as a Group 1 carcinogen by the International Agency for Research on Cancer (IARC)
Second most common cause of lung cancer
Causes lung cancer even in never-smokers

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Particulate Matter

Particulate matter comes in different sizes. Very small particles called (PM 2.5) come from the burning fossil fuels

in factories,
power plants, and
diesel- and gasoline-powered motor vehicles
gas stoves
fires

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Particulate Matter

Particulate matter comes in different sizes. Very small particles called (PM 2.5) come from the burning fossil fuels

in factories,
power plants, and
diesel- and gasoline-powered motor vehicles
gas stoves
fires

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PM 2.5:

A Class 1 Carcinogen

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PM 2.5 Mechanism of Injury

Impaired respiratory function�Cardiovascular inflammation
Endothelial dysfunction
Platelet aggregation
Vasoconstriction �Bronchitis, pneumonitis, COPD, asthma�Cardiovascular diseases�Lung cancer

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Turner, C. CA CANCER J CLIN 2020; 70:460–4

CANCER

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Estimated Hazard Ratios Associated with 10 mcg/^m3 increase of PM 2.5�Coleman N, et al Cancer Causes & Control (2020) 31:767–776

US National Health Interview Survey and National Death Index follow-up

635,539 individuals surveyed from 1987 to 2014.
Included a sub-cohort of 341,665 never-smokers

HR (95% CI)	Full cohort (N= 635,539)

Lung cancer	1.13 (1.0-1.26)

^{*p< 0.05 after adjusting for multiple variables}

I’m now going to show you some of the studies that show that exposure to high levels of PM2.5 is associated with lung cancers, even in people who have never smoked.

This a study involving over 600,000 people, over 24 years, and found that increases in PM2.5 were associated with a significant increase in lung cancer risk, which was statistically significant after adjusting for multiple comparisons. CLICK

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All hazard ratios are adjusted for age, sex, ethnicity, income, education, race, marital status, BMI, smoking, urban versus rural, Census Regent’s, and survey year.

It is unknown whether or not the larger HR for never-smokers is due to different susceptibility, underlying biology, or simply due to differences in baseline risk. Given the large effect of smoking on lung cancer, the underlying or baseline mortality risk for lung cancer in never-smokers is much smaller than for smokers. As such the proportional hazard (an estimate of relative risk) associated with PM2.5 exposure would likely be larger in never-smokers than in smokers. The results from this study are comparable to a recent meta-analysis of cohorts examining PM 2.5 -lung cancer mortality (HR 1.13, 95% CI 1.07–1.20)

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Estimated Hazard Ratios Associated with 10 mcg/^m3 increase of PM 2.5�Coleman N, et al Cancer Causes & Control (2020) 31:767–776��

US National Health Interview Survey and National Death Index follow-up

635,539 individuals surveyed from 1987 to 2014.
Included a sub-cohort of 341,665 never-smokers

HR (95% CI)	Full cohort (N= 635,539)	Never-smoker cohort (n=341.665)

Lung cancer	1.13 (1.0-1.26)	1.73 (1.2-2.49)

^{P< 0.05 after adjusting for multiple variables}

They analyzed a subset of over 340,000 never-smokers and found that they too had an increased risk of developing lung cancer, even after adjusted for such variables as age, sex, ethnicity, income, education, race, BMI, smoking, urban versus rural.

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It is unknown whether or not the larger HR for never-smokers is due to different susceptibility, underlying biology, or simply due to differences in baseline risk. Given the large effect of smoking on lung cancer, the underlying or baseline mortality risk for lung cancer in never-smokers is much smaller than for smokers. As such the proportional hazard (an estimate of relative risk) associated with PM2.5 exposure would likely be larger in never-smokers than in smokers. The results from this study are comparable to a recent meta-analysis of cohorts examining PM 2.5 -lung cancer mortality (HR 1.13, 95% CI 1.07–1.20)

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�IARC Rates Diesel as Carcinogenic to Humans with an Increased Risk for Lung Cancer: �Group 1 Carcinogen��

Diesel Exhaust in Miners Study (DEMS)

A Cohort Mortality Study With Emphasis on Lung Cancer

HR for lung cancer mortality increased with increasing exposure for ever-underground workers with 5 or more years of tenure (HR = 5.01, 95% CI = 1.97 to 12.76)

The Diesel Exhaust in Miners Study: A Nested Case–Control Study of Lung Cancer and Diesel Exhaust

Risk was approximately three times greater (OR = 3.20, 95% CI = 1.33 to 7.69) than that among workers in the lowest quartile of exposure.
Never smokers:

IARC Monograph; June 12, 2012

Atttfield et al: JNCI; 104: 2012

Silverman, et al JNCI: 104: 2012

Tertiles (per mcg/m³⁾)	<8	8-303	>304
Odds ratio	1.0	1.47 (95% CI: 0.29- 7.50)	7.30 (95% CI: 1.46-36.57)

Christopher Portier, Chairman of the IARC working Group, stated that “The scientific evidence was compelling and the Working Group’s conclusion was unanimous: diesel engine exhaust causes lung cancer in humans.”

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The Relationship Between Air Pollution and Lung Cancer in Nonsmokers in Taiwan�Tseng Journal of Thoracic Oncology; Vol. 14 784-792

Northern Taiwan

Southern Taiwan

Visibility (km)

This is a study from Taiwan, comparing the northern section and southern section. This graph shows the amount of air pollution in southern Taiwan, in red compared to northern Taiwan, in green. You can see that until about 1992, the visibility in northern Taiwan was significantly worse than in southern Taiwan. CLICK

But after 1992, things changed; the visibility in northern Taiwan improved, while the visibility in southern Taiwan got worse. What happened? In northern Taiwan, where the city of Taipei is, they constructed a mass transit rail system, and factories were moved outside the city. In contrast, the petrochemical industry started developing in southern Taiwan, and as it did, visibility got worse. CLICK

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This is a study from Taiwan, comparing the northern section and southern section. The tow graphs on the left show the amount of air pollution in southern Taiwan, in red compared to northern Taiwan, in green. You can see that until about 1992, the visibility in northern Taiwan was singnifcantly worse than in southern Taiwan.

But after 1992, things changed; the visibility in northern Taiwan improved, while the visibility in southern Taiwan got worse. What happened? In northern Taiwan, where the city of Taipei is, they constructed a mass transit rail system, and factories were moved outside the city. In contrast, the petrochemical industry started developing in southern Taiwan, and as it did, visibility got worse.

Before 1992, Taipei city and Northern Taiwan (the green line) had poor atmospheric visibility because of the growing population, trafﬁc volumes, and industrial factories. However, it improved between 1993 and 2003 because of the construction and expansion of a mass transit rail system in Taipei, and because factories were moved outside Taipei

In contrast, since 1970, the petrochemical industry has been rapidly developing in Southern Taiwan (the red line) and atmospheric visibility declined between 1980 and 2000 CLICK

Here you can see age adjusted incidence o lung adenocarcinoma in Northern and Southern Taiwan during that period of time.

The other point I wanted to make CLICK is to notice that there was roughly a 15 year time lag between increasing exposure to pollution and an increasing incidence of lung cancer

Figure 2. Trends in atmospheric visibility from 1980 to 2005 and age-adjusted incidence of lung adenocarcinoma from 2004 to 2015. (A) Visibility (km); (B) proportion of days with a visibility less than 10 km (%); (C) age-adjusted incidence of stages IB to IV adenocarcinoma lung cancer; and (D) age-adjusted incidence of stages IIIB to IV adenocarcinoma lung cancer in northern Taiwan and southern Taiwan.

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The Relationship Between Air Pollution and Lung Cancer in Nonsmokers in Taiwan�Tseng Journal of Thoracic Oncology; Vol. 14 784-792

Age-adjusted incidence of stages IIIB to IV adenocarcinoma lung cancer

Northern Taiwan

Southern Taiwan

Visibility (km)

And as air pollution got worse in southern Taiwan, the incidence of lung cancer went up; and as air pollution got better in northern Taiwan, the incidence of lung cancer got better. And remember – these are people who have. never smoked.

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This is a study from Taiwan, comparing the northern section and southern section. The tow graphs on the left show the amount of air pollution in southern Taiwan, in red compared to northern Taiwan, in green. You can see that until about 1992, the visibility in northern Taiwan was singnifcantly worse than in southern Taiwan.

But after 1992, things changed; the visibility in northern Taiwan improved, while the visibility in southern Taiwan got worse. What happened? In northern Taiwan, where the city of Taipei is, they constructed a mass transit rail system, and factories were moved outside the city. In contrast, the petrochemical industry started developing in southern Taiwan, and as it did, visibility got worse.

Before 1992, Taipei city and Northern Taiwan (the green line) had poor atmospheric visibility because of the growing population, trafﬁc volumes, and industrial factories. However, it improved between 1993 and 2003 because of the construction and expansion of a mass transit rail system in Taipei, and because factories were moved outside Taipei

In contrast, since 1970, the petrochemical industry has been rapidly developing in Southern Taiwan (the red line) and atmospheric visibility declined between 1980 and 2000 CLICK

Here you can see age adjusted incidence o lung adenocarcinoma in Northern and Southern Taiwan during that period of time.

The other point I wanted to make CLICK is to notice that there was roughly a 15 year time lag between increasing exposure to pollution and an increasing incidence of lung cancer

Figure 2. Trends in atmospheric visibility from 1980 to 2005 and age-adjusted incidence of lung adenocarcinoma from 2004 to 2015. (A) Visibility (km); (B) proportion of days with a visibility less than 10 km (%); (C) age-adjusted incidence of stages IB to IV adenocarcinoma lung cancer; and (D) age-adjusted incidence of stages IIIB to IV adenocarcinoma lung cancer in northern Taiwan and southern Taiwan.

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Long-term Ambient Fine Particulate Matter Air Pollution and Lung Cancer in a Large Cohort of Never Smokers�

Turner, Am J Respir Crit Care Med Vol 184. pp 1374–1381, 2011

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Long-term Ambient Fine Particulate Matter Air Pollution and Lung Cancer in a Large Cohort of Never-Smokers�Turner, et al; Ca Cancer J Clin 2020; 70

26-year prospective study of a large cohort of lifelong never-smokers.
Each 10 mcg/m3 increase in PM2.5 concentrations was associated with a 15–27% increase in lung cancer mortality.

This was another study that examined the association between mean long term ambient PM2.5 concentrations and lung cancer mortality in never smokers. They found that each 10 mcg/m3 increase in PM2.5 concentrations was associated with a 15–27% increase in lung cancer mortality.

They then looked at multiple cohort studies– here is the forest plot -- CLICK –

And found a 13% - 14% increase risk of dying of lung cancer

FIGURE 2. Estimated Adjusted Hazard Ratios (HRs) and 95% Confidence Intervals for Lung Cancer Mortality per 10 µg/m 3 Elevation in PM 2.5 From Multiple Cohort Studies. Black diamonds represent selected studies, with the size of the diamond proportional to the relative weight in the random effect estimate using selected studies. The red squares represent random effects meta-estimates. The black line is a reference line at an HR of 1.00. The red line is a reference line at an HR equal to the random-effects meta-estimate using the selected studies. ACS indicates American Cancer Society; ACS CPS II, American Cancer Society Cancer Prevention Study II; ASHMOG, Adventist Health Air Pollution Study; CanCHEC, Canadian Census Health and Environment Cohort; Com. Health, Community Health; DUELS, Dutch Environmental Longitudinal Study; ESCAPE, European Study of Cohorts for Air Pollution Effects; NECSS, National Enhanced Cancer Surveillance System; NHIS, National Health Interview Survey; NLCS-Air, Netherlands Cohort Study on Diet and Cancer-Air Pollution Study; PAARC, French Air Pollution and Chronic Respiratory Diseases study; PM2.5 , particulate matter particles ≤2.5 µm in aerodynamic diameter; TB, tuberculosis. Source: Modified and updated from: Pope CA III, Coleman N, Pond ZA, Burnett RT. Fine particulate air pollution and human mortality: 25+ years of cohort studies. Environ Res. 2020;183:108924. 60 Reprinted under a CC BY-NC-ND 4.0 Creative Commons license.

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Air Pollution Shortens Lung Cancer Survival��Eckel SP, et al. Thorax 2016;71:891–898.

Risk of Dying with Localized Exposure

RISK of DYING

PM2.5 concentration

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		Outdoor					Indoor
Burning of Fossil Fuels (80%r - 85%)					Consequences of Climate Change	Ambien	Burning of rNatural Gas Methane	Chemicals from Products
Gas	Diesel		Coal	Jet fuel	Wildfires	Sand, sea salt, etc

Common

Sources of Air Pollution

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		Outdoor					Indoor
Burning of Fossil Fuels (80%r - 85%)					Consequences of Climate Change	Ambien	Burning of rNatural Gas Methane	Chemicals from Products
Gas	Diesel		Coal	Jet fuel	Wildfires	Sand, sea salt, etc

Common

Sources of Air Pollution

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Wildfires

Wildfire season in the western US is 105 days longer than it was in 1970
Due to droughts and increasing heat
California:

7/2024: five times as many acres burned compared to the five-year average
1/2025: ?

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https://www.unep.org/resources/report/spreading-wildfire-rising-threat-extraordinary-landscape-fires

North America was the only region in the world where air quality worsened between 2019 and 2020, due to wildfires that burnt through a record 4.3 million areas of the United States

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Long-term exposure to wildfires & cancer incidence in Canada: a population-based observational cohort study��Korsiak, et al; Lancet Planet Health 2022; 6: e400-09

Compared to unexposed populations, cohort members exposed to a wildfire within 50 km of residential locations in the past 10 years:
Lung cancer: 4∙9% relatively higher incidence (adjusted [HR] 1∙049, 95% CI 1∙028–1∙071)
Brain tumors: 10% relatively higher incidence (adjusted HR 1∙100, 1∙026–1∙179)

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https://www.washingtonpost.com/weather/2021/10/20/wildfire-smoke-deaths-eastern-us/

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Mostly carbonaceous

5–20% elemental carbon
50% organic carbon

More oxidative potential due to presence of more polar compounds

Result:
More free radicals
More oxidative stress
More inflammation

PM2.5 from Wildfires

Aguilera, Nature Communications, 2021

A recent study found that p.m. 2.5 from wildfires is 10 times more harmful than p.m. 2.5 from other sources, because it contains more carbon and has more oxidative potential than ambient urban particulate

due to the presence of more polar organic compounds.

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These compounds in wildﬁre smoke tend to generate more free radicals and thus have a greater potential to cause inﬂammation and oxidative stress in the lung than urban ambient particulate from the same region .

https://www.bloomberg.com/news/articles/2021-03-16/record-breaking-wildfires-made-north-american-air-worse-in-2020?sref=wINQCNXe�

From Grist

Aguilera, R ,Nature Communications,| https://doi.org/10.1038/s41467-021-21708-0

A recent study found that p.m. 2.5 from wildfires is 10 times more harmful than p.m. 2.5 from other sources.

Though the differential toxicity of wildﬁre PM 2.5 as compared to other ambient sources of PM 2.5 is not well understood 11–13 , recent animal toxicological studies suggest that particulate matter from wildﬁres is more toxic than equal doses from other sources such as ambient pollution 14,15 . In vitro and in vivo studies have shown that mechanisms that may explain wildﬁre-speciﬁc PM higher toxicity include inﬂammation, oxidative stress 15 , or increased respiratory infection by altering pulmonary macrophages activity 16 . Wildﬁre particulate matter is mostly carbonaceous (with 5–20% elemental carbon and at least 50% organic carbon 17,18 ) and has more oxidative potential than ambient urban particulate due to the presence of more polar organic compounds 19 . All the above compounds in wildﬁre smoke tend to generate more free radicals and thus have a greater potential to cause inﬂammation and oxidative stress in the lung than urban ambient particulate from the same region 20,21 .

https://www.bloomberg.com/news/articles/2021-03-16/record-breaking-wildfires-made-north-american-air-worse-in-2020?sref=wINQCNXe�

From Grist

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Where is all this �AIR POLLUTION coming from?

From the burning of fossil fuels

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Where is CLIMATE CHANGE coming from?

From the burning of fossil fuels

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Effects of Wildfire Events on California Radiation Oncology Clinics and Patients��Lichter, et al; Advances in Radiation Oncology; 2024: 9

Survey of California radiation oncologists to evaluate emergency preparedness and the effect of wildfires on RT services between 2017 and 2022
61% of respondents reported being affected by a wildfire
Effects on practice:

18% reported a clinic closure
29% reported staffing shortages
24% reported being forced to transfer patients

Effects on patients:

Cancel or reschedule treatments 53%
Having to evacuate: 55%

Only 47% reported their workplace had a wildfire emergency preparedness plan

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Association of Wildfire Exposure While Recovering From Lung Cancer Surgery With Overall Survival

Zhang, et al, JAMA Oncol; Published on line July 27,2023

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Impact of Wildfire Disasters on Survival of Lung Cancer Patients Undergoing Radiation Therapy��Lichter, K. et al�� JCO Oncology Practice No 11 suppl 11.1.2023

Patients with locally advanced NSCLC who had a wildfire disaster declared in the county of the treatment facility within 12 weeks of the RT start date

Exposed patients: N=1419
Unexposed patients: N=226.719

Survival of exposed patients compared to unexposed patients: HR = 1.03; 95% CI= 1.01, 1.06

DOI: 10.1200/OP.2023.19.11_suppl.302 JCO Oncology Practice 19, no. 11_suppl (November 01, 2023) 302-302.

Published online October 26, 2023.

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Association of Wildfire Exposure While Recovering From Lung Cancer Surgery With Overall Survival��Zhang, D et al JAMA Oncology; Published on line 7.27.2023

JAMA Oncol. doi:10.1001/jamaoncol.2023.2144 Published online July 27, 2023.;

In another study, the same authors, they found that being exposed to wildfire smok

In another study by the same authors, they found that being exposed to wildfire smoke, while recovering from lung cancer, surgery was associated with a worst survival than people who were recovering from surgery, but has not been exposed to wildfire smoke.

For those indidivuals who were 7-12 months out forom their surgery, the risk of dying was 14%. CLICK For those 4-6 months out, it was 39%. And for those 0-3 months out, 43%

https://doi.org/10.1001/jamaoncol.2023.2144

In another study, they found that being exposed to wildfire smoke while recovering from lung cancer surgery, was associated with a worst survival than people who were recovering from surgery, but has not been exposed to wildfire smoke.

For those individuals who were 7 to 12 months out from their surgery, the risk of dying was 14% click

For those 4 to 6 months out it was 39%. Click and for those 0 to 3 months out from their surgery, it was 43%.

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A total of 466 912 individuals included in the study

(249 303 female and [53.4] and 217 609 male [46.6%]; mean [SD] age at diagnosis, 67.3 [9.9] years), with

48 582 (10.4%) first exposed to a wildfire between 0 and 3 months,

48 328 (10.6%) between 4 and 6 months, and

71 735 (15.3%) between 7 and 12 months following NSCLC surgery. I

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So what can we do???

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Lots! Personal actions

Ride gas-powered vehicles less frequently

Walk/bike more
Telecommute
Electric cars
Zoom meeting

Use clean energy

Solar
Wind
Geothermal
Electricity

Eat less red meat

Lots! Things ware may things w can do to make an impact and serve as good role models. These are all pretty straightforward, such cutting back on riding gas powered vehicles and using more clean energy

Something we haven't talked about today .. the huge impact our agriculatural system has on air pollution and environmental degradation. A big impact we all could have is by eating less red meat, and reducing food waste

Speak up! Advocate!

Not only to your community, but very importantly, to your health care system, since in the US, health care represents about 8% of carbon emmissions and professional organizations. And ask your professional organizations to take a more active, unified voice to protect their cancer patients.

As representatives of health care, we have a powerful voice, and as representatives of how climate change effects cancer care, we have a very powerful voice. The effects of climate change on health have been pretty much ignored up to now– but how climate change will affect a person’s health, or the health of their grandkids, speaks to people. CLICK

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Lots!

Personal actions

Speak up! Advocate!

Locally
Your health care system
Professional organizations

I would also argue we need to speak up. As health care representatives, we are powerful messengers. As cancer care professionals, we are VERY powerful messengers. The one common message that is universally true across all populations is that people want to protect their children and grandchildren

Very importantly, we need to advocate to our health care systems, since in the US, health care represents about 8% of carbon emissions

Also, ask your professional organizations to take a more active, unified voice to protect their cancer patients.

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As representatives of health care, we have a powerful voice, and as representatives of how climate change effects cancer care, we have a very powerful voice. The effects of climate change on health have been pretty much ignored up to now– but how climate change will affect a person’s health, or the health of their grandkids, speaks to people.

We are trusted messengers! Particularly when if involves cancer. CLICK

Too busy? Not enough bandwith to take this on? Then support non-profit organizations who. have the time, energy and know-how to do it for you. CLICK

And perhaps most importantly .... vote responsibly

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Lots!

Personal actions

Speak up! Advocate!

Support climate change and environmental non-profits

Too busy? Not enough band with to take this on? Then support non-profit organizations who. have the time, energy and know-how to do it for you. And perhaps most importantly...CLICK

Vote responsibly

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Lots! Take personal responsibility – do your share. Decrease use of gas power vehicles, switch to clean energy sources CLLICK

Speak up! Advocate!

Not only to your community, but very importantly, to your health care system, since in the US, health care represents about 8% of carbon emmissions and professional organizations. And ask your professional organizations to take a more active, unified voice to protect their cancer patients.

As representatives of health care, we have a powerful voice, and as representatives of how climate change effects cancer care, we have a very powerful voice. The effects of climate change on health have been pretty much ignored up to now– but how climate change will affect a person’s health, or the health of their grandkids, speaks to people. CLICK

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“Never doubt that a small group of thoughtful committed citizens can change the world; indeed, it is the only thing that ever has”

Margaret Mead

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Thank You for Your Attention!!!