CORRECTION: Outdoor air pollution may increase non-lung cancer risk in older adults

HARVARD T.H. CHAN SCHOOL OF PUBLIC HEALTH

 NEWS RELEASE 11-AUG-2023

*This press release was amended on August 9, 2023. Due to a mistake in interpretation of data, the previous version of the release stated the study found that NO2 exposure is associated with a decreased risk of breast cancer. The authors have confirmed that the results showed that NO2 exposure is associated with an increased risk of breast cancer.

 

Key points:

• A cohort study of millions of Medicare beneficiaries found that chronic exposures to PM2.5 and NO2 over a 10-year period increased the risk of developing colorectal and prostate cancers.
• Even in areas with low pollution levels, researchers found substantial associations between exposures to these pollutants and the risk of developing colorectal and prostate cancers, in addition to breast and endometrial cancers.

Boston, MA—Chronic exposure to fine particulate air pollutants (PM2.5) and nitrogen dioxide (NO2) may increase non-lung cancer risk in older adults, according to a study led by Harvard T.H. Chan School of Public Health. In a cohort study of millions of Medicare beneficiaries, the researchers found that exposures to PM2.5 and NO2 over a 10-year period increased the risk of developing colorectal and prostate cancers. The researchers also found that even low levels of air pollution exposure may make people particularly susceptible to developing these cancers, in addition to breast and endometrial cancers.

“Our findings uncover the biological plausibility of air pollution as a crucial risk factor in the development of specific cancers, bringing us one step closer to understanding the impact of air pollution on human health,” said Yaguang Wei, research fellow in the Department of Environmental Health. “To ensure equitable access to clean air for all populations, we must fully define the effects of air pollution and then work towards reducing it.”

The study was published online August 1, 2023, in Environmental Epidemiology.

While air pollution has been established as a risk factor for lung cancer, and a link to breast cancer risk has been emerging, few studies have looked at its effects on prostate, colorectal, and endometrial cancer risk.

Researchers analyzed data from national Medicare beneficiaries aged 65 or older, collected from 2000 to 2016. All subjects were cancer-free for at least the initial 10 years of the study period. The researchers created separate cohorts for each type of cancer—breast, colorectal, endometrial, and prostate—with between 2.2 million and 6.5 million subjects in each cohort. Separate analyses looked at cancer risk under the impacts of air pollutants for various subgroups by factors including age, sex (for colorectal cancer only), race/ethnicity, average BMI, and socioeconomic status.

Drawing from a variety of air pollution data sources, the researchers developed a predictive map of PM2.5 and NO2 concentrations across the contiguous U.S. This was then linked to beneficiaries’ residential ZIP codes to enable the researchers to estimate individual exposures over a 10-year period.

Findings from the nationwide analysis showed that chronic PM2.5 and NO2 exposures increased the risk of developing colorectal and prostate cancers but were not associated with endometrial cancer risk. For breast cancer, NO2 exposure was associated with an increased risk, while the association for PM2.5 was inconclusive. The researchers suggested that the mixed associations may be due to variations in the chemical composition of PM2.5, which is a complex mixture of solid and liquid particles.

When the analysis was restricted to regions where air pollution levels were significantly below national standards and the composition of PM2.5 remained fairly stable, their effect on breast cancer risk was more pronounced. Stronger associations between exposures to both pollutants and endometrial cancer risk were also found at lower pollution levels.

In their analysis of risk by subgroups, the researchers found evidence suggesting that communities with higher average BMI may face disproportionately higher risk of all four cancers from NO2 exposure, and that Black Americans and those enrolled in Medicaid may be more susceptible to cancer risks (prostate and breast, respectively) from PM2.5 exposure.

The researchers noted that even communities with seemingly clean air were not immune to cancer risk. They found substantial associations between exposure to the two pollutants and the risks of all four cancers even at pollution levels below newly updated World Health Organization guidelines (which are lower than current U.S. standards).

“The key message here is that U.S. air pollution standards are inadequate in protecting public health,” said senior author Joel Schwartz, professor of environmental epidemiology. “The Environmental Protection Agency recently proposed stricter standards for PM2.5, but their proposal doesn’t go far enough in regulating this pollutant. Current NO2 standards are also woefully inadequate. Unless all of these standards become much, much stricter, air pollution will continue to result in thousands of unnecessary cases of multiple cancers each year.”

Other Harvard Chan School authors include Edgar Castro, Cristina Su Liu, Xinye Qiu, James Healy, and Bryan Vu.

Funding for the study came from the National Institutes of Health grants R01ES032418 and P30ES000002.

“Additive effects of ten-year exposures to PM2.5 and NO2 and primary cancer incidence in American older adults,” Yaguang Wei, Mahdieh Danesh Yazdi, Tszshan Ma, Edgar Castro, Cristina Su Liu, Xinye Qiu, James Healy, Bryan N. Vu, Cuicui Wang, Liuhua Shi, Joel Schwartz, Environmental Epidemiology, online August 1, 2023, doi: 10.1097/EE9.0000000000000265

Visit the Harvard Chan School website for the latest news, press releases, and multimedia offerings.

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Harvard T.H. Chan School of Public Health brings together dedicated experts from many disciplines to educate new generations of global health leaders and produce powerful ideas that improve the lives and health of people everywhere. As a community of leading scientists, educators, and students, we work together to take innovative ideas from the laboratory to people’s lives—not only making scientific breakthroughs, but also working to change individual behaviors, public policies, and health care practices. Each year, more than 400 faculty members at Harvard Chan School teach 1,000-plus full-time students from around the world and train thousands more through online and executive education courses. Founded in 1913 as the Harvard-MIT School of Health Officers, the School is recognized as America’s oldest professional training program in public health.

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JOURNAL

Environmental Epidemiology

DOI

10.1097/EE9.0000000000000265 

METHOD OF RESEARCH

Observational study

SUBJECT OF RESEARCH

Not applicable

ARTICLE TITLE

Additive effects of ten-year exposures to PM2.5 and NO2 and primary cancer incidence in American older adults

Make Up Your Mind

Sunlight healthy in small quantities

In what has turned out to be a delicate balancing act, the group is advising that while too much time in the sun raises the risk of skin cancer, avoiding it entirely can lead to a deficiency in vitamin D -- and that may elevate the risk of other types of cancers and diseases.

Cancer research is another form of social hysteria fueled by speculation, and lack of empirical data, by the medical pharmaceutical establishment.

Like the myth of Second Hand Smoke and the myth that associates Lung Cancer with smoking.

Cancer is a direct result of the industrial revolution, it is the 'social disease' of capitalism. Of course a little bit of sushine never hurt anyone. Even if the Ozone layer is being depleted. Another result of industrial development.

We ban sunshine and cigarettes because it's easier than banning capitalism.

What does this tell you when the environmental causes of cancer have NOT been studied by the medical pharmecutical establishment till now.

The University of Pittsburgh has created a center—considered the first of its kind anywhere—that will identify environmental causes of cancer. The center’s first director is more than ready to do battle against the disease. In fact, battles are her specialty.

Cancer Crusade

Now as director of the new Center for Environmental Oncology, a collaborative venture between the Graduate School of Public Health and the University of Pittsburgh Cancer Institute, Davis will be fighting to find environmental causes of cancer. The center is the only one of its kind within a cancer institute, says Bernard Goldstein, professor and retiring GSPH dean.

The first project is a collaboration between the center and the University’s Center for Minority Health that will investigate why more young Black women have breast cancer than their White counterparts. They will examine whether beauty products for African American women contribute to increased occurrences of breast cancer. Environment isn’t limited to forests, rivers, lakes, fields, and sky. It is what we eat, what we use, and what we wear. Beauty products that target African American women often contain estrogen. This affects women in a few ways. For instance, these products might induce early menstruation, and researchers believe that women who menstruate earlier are more likely to get breast cancer. And it’s commonly believed that higher levels of estrogen contribute to increased risks of breast cancer. If African American women are using products that increase the level of estrogen in their bodies, they may be at higher risk.

Bad Air a 'Genetic Risk'

Hamilton scientists' findings show genetic damage from the tiny chemically coated particles of soot regularly spewed out by both industry smokestacks and vehicle exhaust pipes. Soot particles mutate genes in male mice, scientists find. Genetic mutations passed along to offspring via sperm.

Rare lung cancer is leaving sorrowful legacy among working class

Mesothelioma, caused by asbestos, may one day strike rescuers and survivors of World Trade Center attacks

Lung Cancer in a Steel City: A Personal Historical Perspective

In my 1972-74 studies, the male death rate from lung cancer in the most heavily polluted residential zone was 65/100,000, which was 2.83 times higher than the national average of 23/100,000 (2), compared with a 2.42 times higher rate reported in a 1988 study of the same zone involving a correction for age which reduced the ratio to 1.99, along with an additional correction for smoking which further decreased the ratio to 1.40 (5). In terms of my own experience, I suspect that the correction(s) for smoking might be excessive, because the lung cancer victims which I studied had not smoked as many cigarettes as did their "white collar" colleagues. Nevertheless, the main point to remember is that even a suspected over-correction of the raw data revealed a significant difference in lung cancer deaths between the heavily polluted zone and other areas, even when based on "guestimates" calculated 14 years later.

Age and smoking-adjusted lung cancer incidence in a Utah county with a steel mill.

In a recent study of urban air pollution, a Utah county with a steel mill was compared with a county without a steel mill. The result was that 38% of respiratory cancer deaths could be attributed to the air pollution emanating from the mill.


Lung cancer among steelworkers in Ontario.
In internal comparisons within the steel companies, increased lung cancer risk was observed among foundry, coke oven, and pouring pit workers. Retrospective hygiene assessment suggested that the increased risk of lung cancer among steel pourers might be related to the use of tar-based mold coating agents or to exposure to mineral fibers.

Male Breast Cancer
Men who work in steel mills, blast furnaces, rolling mills, or other environments of intense heat have a slightly increased incidence of breast cancer ...


Pollution Poses High Cancer Risk

Residents in Indiana’s heavily industrialized areas - particularly Lake County and Indianapolis - face an elevated risk of developing cancer from breathing air pollution, according to a new federal analysis.

The study released by the U.S. Environmental Protection Agency is the agency’s most ambitious look to date at cancer risks from breathing chemicals.

In its National Air Toxics Assessment, the EPA studied 133 chemicals emitted in 1999 by businesses and traffic. It outlines lifetime cancer risks in states, counties and census tracts.

Find blog posts, photos, events and more off-site about:
Sunshine, Sun, sunbathing, tanning, tan, cancer, capitalism, industrial-pllution, smoking, lung-cancer, breast-cancer, hamilton, steel-mills, asbestos,

Doctors say breathing toxic air in Delhi is like smoking 10 cigarettes a day and urgent solutions are needed

By Charmaine Manuel

abc.net.au

1/1/2022

During December, Delhi's daily PM2.5 levels were, on average, nearly 14 times higher than the World Health Organization recommends.

(Reuters: Adnan Abidi)

Months after the Delta variant ravaged India's capital, Delhi, the city's residents are taking refuge indoors once more.

Key points:

Air pollution is a health concern for children and adults in Delhi

Experts say breathing toxic air is equivalent to smoking multiple cigarettes a day

Clean air activists say urgent solutions are needed


But this time, they aren't just shielding themselves from a dangerous virus. They're also protecting themselves from the city's toxic air.

Schools, construction sites and some workplaces were closed briefly in November due to heavy air pollution and the country's chief justice has asked the central government to take urgent action on the "very serious" problem in Delhi.

Delhi's air quality has been steadily deteriorating for years, and it is particularly bad during winter when the cool weather traps pollution and smoke, shrouding the city in a thick layer of smog.

This seasonal phenomenon has huge health costs for Delhi's residents, many of whom are now agitating for change.
No one knows what 'real blue skies' and 'real clean air' feels like

Jyoti Pande Lavakare has personally experienced the human cost of Delhi's air pollution crisis.

In 2017, her mother, Kamala, died from lung cancer which, she said, doctors told her was triggered by air pollution.

Jyoti Pande Lavakare's mother, Kamala, died from lung cancer in 2017. (Supplied)

"She got diagnosed and, in three months, she had passed on and that was a very traumatic time," she said.

Ms Lavakare, a clean-air activist and author, always knew that Delhi suffered from poor air quality, but it was only when she returned from years of living in California that she realised just how bad it was.

"I realised that people who were born and raised in India didn't really know what real blue skies looked like and what real clean air smelled and felt like," she said.

Worried about the impact on her young children, Ms Lavakare, a former journalist, threw herself into researching the health consequences of living in a polluted city.

Concerned by what she learned, she founded a not-for-profit called Care for Air to raise awareness of the health impacts of Delhi's dismal air, activism that became more personal after her mother's death.

"Although I knew myself about air pollution, it was all intellectualised in my head," she said.

"But to see her struggle to breathe and to die in that horrific way was something I felt in my heart."

Farmers in India traditionally burn their fields to improve soil fertility. 

(Reuters: Danish Siddiqui)

Why is Delhi's air quality so bad?

There are multiple contributing factors.

Siddharth Singh, an air pollution researcher and the author of The Great Smog of India, noted that while air pollution is a common problem in cities around the world, the kind of pollution seen in Delhi is "unique to India".

Delhi's air quality worsens when farmers in the neighbouring states of Punjab and Haryana burn their fields in the winter months after the harvest to prepare for the next agricultural cycle.

Siddharth Singh says there are several factors that contribute to India's "unique" air pollution. (Supplied)

Mr Singh explained that changing wind directions and slower wind speeds in winter mean that smoke gets trapped instead of being blown towards the sea.

Another factor was pollution emitted from road vehicles and a dependence on coal to generate electricity — India relies heavily on coal because it's readily available and cheap, Mr Singh said.

Northern India also has thousands of small-scale brick manufacturing businesses — which use fire, coal and simple chimneys — that release emissions and dust into the atmosphere and are a "major contributor to the problem", Mr Singh added.

On top of this, the burning of garbage and biomass such as leaves combine to create a "cocktail of air pollutants", Mr Singh said.
Toxic air means no one is a 'true non-smoker' in Delhi

India's government is changing the way it manages pollution by moving to an "airshed" approach.(Reuters: Adnan Abidi)

Breathing in the toxic air of New Delhi has dire consequences for the city's inhabitants.

It can lead to lower life expectancy and an increased chance of lung cancer, among other illnesses, according to professor and medical doctor Arvind Kumar.

As a chest surgeon at Medanta Hospital in Gurugram — a satellite city of Delhi — and founding trustee of the Lung Care Foundation, Dr Kumar has noticed a significant change in the profile of his patients over the past 30 years.

In 1988, 90 per cent of his patients were cigarette smokers and they were mostly men in their 50s and 60s, he said.

But, by 2018, 50 per cent of his lung cancer patients were non-smokers and from a younger demographic: Most were in their 40s, with some in their 30s and a few in their late 20s.

"When I used to operate on patients, I used to see black deposits on the lungs of known smokers. But, when I used to operate on patients for other chest diseases, in non-smokers, it was a rarity to see black lungs," he said.

These days, when he operated on people, finding a normal pink lung was "a rarity", he said.

Dr Arvind Kumar has witnessed a change in the profile of his patients over the past 30 years. (Supplied)

In a city as polluted as Delhi, "there is no true non-smoker", Dr Kumar added.

This is due to the tiny particulate matter known as PM2.5 (with a diameter of 2.5 micrometres or less), air pollution that is so small it can be inhaled into the lungs and enter the bloodstream.

"So, if today the level of PM2.5 is 220 — which is equal to 10 cigarettes — every newborn today will be smoking 10 cigarettes on day one of his or her life," he said.

Over December 2021, Delhi's daily levels of PM2.5 averaged around 205 micrograms per cubic metre, nearly 14 times higher than the threshold prescribed by the World Health Organization's air quality guidelines.

Ms Lavakare was particularly concerned about the impact on Delhi's children, saying the air is so polluted that "every newborn is a smoker from the day they're born".

"You're setting up your young and your youth for failure," she said.

A boom in air purifiers and oxygen bars

People are paying to breathe in fresh oxygen at oxygen bars in Delhi.

 (Reuters: Anushree Fadnavis)

One of the offshoots of the air pollution crisis is the rise in products and businesses catering to the need for clean, fresh air.

"Air purifiers are a booming industry today," Dr Kumar said.

Cities like Delhi have also seen a rise in oxygen bars, where customers can pay to breathe in pure oxygen.

At one oxygen bar in Delhi, customers can pay 700–1300 rupees ($13–$24) to breathe in flavoured oxygen for around 15 minutes.

Dr Kumar described these ventures as "opportunistic industries" that are trying to "cash in on this health crisis".

Mr Singh noted that, while wealthier residents have the option of staying indoors or purchasing air purifiers, lower socio-economic groups are more exposed to air pollution.

"The poor tend to work closer to the roads. They tend to work closer to the brick-manufacturing units. They tend to work at construction sites, so their exposure to pollution is obviously much, much higher," he said.
Solutions to avoid 'a dystopian future'

In response to the country's air pollution problem, India's central government launched the National Clean Air Program (NCAP) in 2019.

The NCAP targets air pollution in around 132 cities in India and aims to reduce pollution concentrations by 2024.

Mr Singh was not optimistic about NCAP's success because air pollution "is not just an urban problem".

Some experts say "smog towers", which are basically 20-metre-tall air purifiers, are ineffective.

(Reuters: Adnan Abidi)

The ABC contacted the Environment Minister in the Delhi government, Gopal Rai, as well as pollution control entities at the state and central government level but did not receive a response.

What was needed, Mr Singh said, was "a shift from an urban approach to an airshed approach".

An airshed, he explained, was a region with "common geographical and meteorological traits that make air pollution in that region very similar".

India's Environment Minister, Bhupender Yadav, recently announced the government would revise its approach to air pollution and would focus on airsheds instead of urban centres.

The Delhi government has also attempted to tackle air pollution in the city by building smog towers, which are designed to purify the air around them.

Both Dr Kumar and Ms Lavakare consider this solution to be ineffectual and a waste of money.

Dr Kumar said air pollution could not be solved by allowing the air to be polluted and then cleaning it.

It was the sources of pollution that needed to be controlled, he stressed.

But there was also the question of political will.

Air pollution was "not a major electoral issue", Mr Singh said, because there were more-pressing developmental challenges such as "poverty, economic growth, jobs, inflation" along with other political and cultural issues.

Jyoti Pande Lavakare became a clean-air activist and is worried about the impact of air pollution on her family. (Supplied)

Air pollution is the second crisis Delhi's residents have lived through in 2021 after the pandemic.

However, Ms Lavakare said that its government was not taking air pollution as seriously as COVID-19 and that it had fallen to civil society groups such as hers to do the government's job in spreading awareness.

"It's really a dystopian future unless the government gets its act together," she said.

How air pollution alters lung tissue, increasing cancer susceptibility

Findings highlight a potential new target for preventing lung disease caused by air pollution.

Peer-Reviewed Publication

ELIFE

 

IMAGE: INHALED FINE PARTICULATE MATTER (SHOWN HERE IN RED) PULLS STRINGS OF COLLAGEN TO DISTURB THE IMMUNE DEFENCE IN MICE WITH LUNG CANCER CELLS. THIS ACTIVITY DELAYS THE MOVEMENT OF CYTOTOXIC T-CELLS (PURPLE) AS THEY MIGRATE TOWARDS THE CANCER CELLS (GREEN) TO DESTROY THEM. view more 

CREDIT: WANG ET AL. (CC BY 4.0)

Scientists have identified a mechanism that explains how fine air pollution particles might cause lung cancer, according to a study published today in eLife.

The findings could lead to new approaches for preventing or treating the initial lung changes that lead to the disease.    

Tiny, inhalable fine particulate matter (FPM) found in air pollutants has been recognised as a Group 1 carcinogen and a substantial threat to global health. However, the cancer-causing mechanism of FPM remains unclear.

“Despite its potential to cause mutations, recent research suggests that FPM does not directly promote – and may even inhibit – the growth of lung cancer cells,” explains first author Zhenzhen Wang, an associate researcher at Nanjing University (NJU), Nanjing, China, who carried out the  study between labs at NJU and the University of Macau where she was sponsored by a University of Macau Fellowship. “This suggests that FPM might lead to cancer through indirect means that support tumour growth. For example, some studies suggest FPM can prevent immune cells from moving to where they are needed.”

To explore this possibility, Wang and the team collected FPM from seven locations in China and studied its effects on the main immune cells that defend against tumour growth – called cytotoxic T-cells (CTLs). In mice administered with lung cancer cells that were not exposed to FPM, CTLs were recruited to the lung to destroy the tumour cells. By contrast, in the mice whose lungs were exposed to FPM, the infiltration of CTLs was delayed – potentially allowing the tumour cells to establish in lung tissue.

To investigate why the CTLs did not enter the lung as quickly in the FPM-exposed lungs, the team studied both the CTLs themselves and the lung tissue structure. They found that CTLs exposed to FPM still retained their migratory ability, but that FPM exposure dramatically compressed the lung tissue structure and the spaces that immune cells move between. There were also much higher levels of collagen – a protein that provides biomechanical support for cells and tissues. When the team studied the movement of CTLs in the mice, in lung tissue exposed to FPM, CTLs struggled to move, whereas those in the untreated tissue were able to move freely.

Further analysis of the tissue showed that the structural changes were caused by increases in a collagen subtype called collagen IV, but the team still did not know how FPM triggered this. They found the answer when they looked more closely at the structural changes to collagen IV and the enzyme responsible for making them – called peroxidasin. This enzyme drives a specific type of cross-linking that exposure to FPM was found to cause and aggravate in the lung tissue. 

“The most surprising find was the mechanism by which this process occurred,” Wang says. “The peroxidasin enzyme stuck to the FPM in the lung, which increased its activity. Taken together, this means that wherever FPM lands in the lung, increased peroxidasin activity leads to structural changes in the lung tissue that can keep immune cells out and away from growing tumour cells.”

“Our study reveals a completely new mechanism by which inhaled fine particles promote lung tumour development,” concludes senior author Lei Dong, Professor at the School of Life Sciences, Nanjing University. “We provide direct evidence that proteins that stick to fine particulate matter can cause a significant and adverse effect, giving rise to pathogenic activity. Our discovery that peroxidasin is the mediator of this effect in lung tissue identifies it as a specific and unexpected target for preventing lung disease caused by air pollution.”

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eLife

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eLife transforms research communication to create a future where a diverse, global community of scientists and researchers produces open and trusted results for the benefit of all. Independent, not-for-profit and supported by funders, we improve the way science is practised and shared. From the research we publish, to the tools we build, to the people we work with, we’ve earned a reputation for quality, integrity and the flexibility to bring about real change. eLife receives financial support and strategic guidance from the Howard Hughes Medical Institute, Knut and Alice Wallenberg Foundation, the Max Planck Society and Wellcome. Learn more at https://elifesciences.org/about.

To read the latest Cancer Biology research published in eLife, visit https://elifesciences.org/subjects/cancer-biology.

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JOURNAL

eLife

DOI

10.7554/eLife.75345 

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

Animals

ARTICLE TITLE

Air pollution particles hijack peroxidasin to disrupt immunosurveillance and promote lung cancer

ARTICLE PUBLICATION DATE

19-Apr-2022

AIR POLLUTION ENVIRONMENTAL TOXINS

‘But I never smoked’: A growing share of lung cancer cases is turning up in an unexpected population


By SHARON BEGLEY @sxbegle

JANUARY 26, 2021

Mandi Pike near her home in Edmond, Okla. Pike, a never-smoker, was diagnosed with lung cancer in November 2019.NICK OXFORD FOR STAT


Sharon Begley died of complications of lung cancer on Jan. 16, just five days after completing this article. She was a never-smoker.

Breast cancer wouldn’t have surprised her; being among the 1 in 8 women who develop it over their lifetime isn’t statistically improbable. Neither would have colorectal cancer; knowing the risk, Mandi Pike “definitely” planned to have colonoscopies as she grew older.

But when a PET scan in November 2019 revealed that Pike, a 33-year-old oil trader, wife, and mother of two in Edmond, Okla., had lung cancer — she had been coughing and was initially misdiagnosed with pneumonia — her first
reaction was, “but I never smoked,” she said. “It all seemed so surreal.”

Join the club. Cigarette smoking is still the single greatest cause of lung cancer, which is why screening recommendations apply only to current and former smokers and why 84% of U.S. women and 90% of U.S. men with a new diagnosis of lung cancer have ever smoked, according to a study published in December in JAMA Oncology. Still, 12% of U.S. lung cancer patients are never-smokers.

Scientists disagree on whether the absolute number of such patients is increasing, but the proportion who are never-smokers clearly is. Doctors and public health experts have been slow to recognize this trend, however, and now there is growing pressure to understand how never-smokers’ disease differs from that of smokers, and to review whether screening guidelines need revision.

“Since the early 2000s, we have seen what I think is truly an epidemiological shift in lung cancer,” said surgeon Andrew Kaufman of Mount Sinai Hospital in New York, whose program for never-smokers has treated some 3,800 patients in 10 years. “If lung cancer in never-smokers were a separate entity, it would be in the top 10 cancers in the U.S.” for both incidence and mortality.

A 2017 study of 12,103 lung cancer patients in three representative U.S. hospitals found that never-smokers were 8% of the total from 1990 to 1995 but 14.9% from 2011 to 2013. The authors ruled out statistical anomalies and concluded that “the actual incidence of lung cancer in never smokers is increasing.” Another study that same year, of 2,170 patients in the U.K., found an even larger increase: The proportion of lung cancer patients who were never-smokers rose from 13% in 2008 to 28% in 2014.

“It is well-documented that approximately 20% of lung cancer cases that occur in women in the U.S. and 9% of cases in men, are diagnosed in never-smokers,” Kaufman said.

To a great extent, this is a function of straightforward math, said epidemiologist Ahmedin Jemal of the American Cancer Society. Fewer people smoke today than in previous decades — 15% in 2015, 25% in 1995, 30% in 1985, 42% in 1965. Simply because there are fewer smokers in the population, out of every 100 lung cancer patients, fewer will therefore be smokers. And that means more of them will be never-smokers.

There are also hints that the absolute incidence of lung cancer in never-smokers has been rising, said oncologist John Heymach of MD Anderson Cancer Center. Some data say it has, but other data say no. The stumbling block is that old datasets often don’t indicate a lung cancer patient’s smoking status, Heymach said, making it impossible to calculate what percent of never-smokers in past decades developed lung cancer.

Jemal, however, cautions that it is not the case that a never-smoker has a greater chance of developing lung cancer today than never-smokers did in the past.

Current cancer screening guidelines recommend a CT scan for anyone 50 to 80 years old who has smoked at least 20 pack years (the equivalent of one pack a day for 20 years, or two packs a day for 10 years, and so on) and who is still smoking or quit less than 15 years ago. Screening is not recommended for never-smokers because the costs of doing so are deemed greater than the benefits, Jemal said; thousands of never-smokers would have to be screened in any given year to find one lung cancer.

Still, low-dose CT can catch lung cancer in a significant number of never-smokers. A 2019 study in South Korea diagnosed lung cancer in 0.45% of never-smokers, compared to 0.86% of smokers. The researchers urged policymakers to “consider the value of using low-dose CT screening in the never-smoker population.”

“It used to be that the high-risk group” for whom CT screening is recommended “was the vast majority of lung cancer patients,” Heymach said. “But now that so many lung cancer cases are in nonsmokers, there is absolutely a need to reevaluate the screening criteria.”

Related:
Lung cancer deaths are declining faster than new cases. Advances in treatment are making the difference

Researchers are trying to improve screening by reducing the incidence of false positives — when CT finds lung nodules “or an old scar that you got 20 years ago,” he said. Those don’t pose a threat but have to be biopsied to ascertain that. Screening never-smokers would also be more efficient than it is today “if we could identify who, among nonsmokers, are at higher risk,” he said.

Cancer doctors already know part of the answer: women. Worldwide, 15% of male lung cancer patients are never-smokers. But fully half of female lung cancer patients never smoked. And women never-smokers are twice as likely to develop lung cancer as men who never put a cigarette to their lips.

Beyond sex, “nothing stands out as a single large risk factor that, if we only got rid of it, we would solve the problem” of lung cancer in never-smokers, said Josephine Feliciano, an oncologist at Johns Hopkins University School of Medicine. “But air pollution, radon, family history of lung cancer, [and] genetic predispositions” all play a role. Chronic lung infections and lung diseases such as chronic obstructive pulmonary disorder (COPD) also seem to increase risk.

None of those, with the possible exception of genetics and indoor pollution (cooking fires in some low-income countries), affect women more than men. So what’s going on?

At least one biotech believes that biological differences between lung cancer in never-smokers and smokers merits a new drug, and one that might be especially effective in women. “A different disease needs a different drug,” said co-founder and CEO Panna Sharma of Lantern Pharma. In fact Lantern, which is developing a drug for lung cancer in female never-smokers, believes that disease is so different it recently tried to convince the U.S. Food and Drug Administration to designate it an orphan disease, said Sharma.

Called LP-300, the Lantern drug increased overall survival from 13 months to more than 27, compared to chemotherapy alone, in female nonsmokers, in a small trial. It “targets molecular pathways that are more common in female nonsmokers than in any other group,” said Sharma, targeting the mutations EGFR, ALK, MET, and ROS1 (common in never-smokers) directly and boosting the efficacy of other drugs that attack them, such as erlotinib and crizotinib. Lantern plans a larger trial this year.

Smokers’ tumors tend to have more mutations overall, thanks to mutagen-packed cigarette smoke attacking their lungs, but scientists have developed more drugs for never-smokers’ lung tumors than for smokers’. For instance, EGFR and ALK mutations are more common in never-smokers. (Mandi Pike had the EGFR mutation, which was relatively fortunate: A drug targets it, and she has been cancer-free since November.)

STAT+:
Exclusive analysis of biopharma, health policy, and the life sciences.

The targeted drugs bollix up each mutation’s cancer-causing effects. KRAS mutations are more common in smokers’ lung tumors, and there are no KRAS drugs. (A KRAS drug for lung cancer is imminent, though, said thoracic oncologist Ben Creelan of Moffitt Cancer Center in Tampa, Fla.)

According to national guidelines, lung cancer in never-smokers should be treated the same as in smokers, said Creelan. “But I think we should reconsider this,” he said.

Because never-smokers have fewer tumor mutations, it’s harder to find them. So he said clinicians should be more aggressive about looking for actionable mutations in these patients. “I keep looking for a mutation until I find something important,” he said, adding that doctors might need better biopsy material or to use a different sequencing method in never-smokers.

In a cruel twist, the breakthrough drugs that take the brakes off immune cells, which then attack the tumor, are less effective in never-smokers’ lung cancer than in smokers’. The reason seems to be that smokers’ tumors have more mutations, said Mount Sinai’s Kaufman; the mutations often cause the tumor cells to have molecules on their surface that the immune system perceives as foreign and revs up to attack. Never-smokers’ tumors have few, if any, of those “come and get me” molecules. Immune cells therefore ignore them.

“In smokers, conversely, with more mutations, there is more for the immune system to recognize as bizarre and foreign, and so to provoke” an attack, Creelan said.

In contrast, never-smokers’ tumors are more likely to respond to targeted drugs, and as a result to be in remission for a long time or even cured. That’s because with fewer mutations, never-smokers’ tumors are more likely to have an “oncogene addiction,” Heymach explained: They are propelled by only one mutation. The plethora of mutations in smokers’ tumors means that there is usually a back-up cancer driver if a targeted drug eliminates cells with only one. “When a tumor has more and more mutations, blocking one is less likely to have an impact,” Heymach said. “But in nonsmokers, it can.”

Heymach called for more funding to study lung cancer in never-smokers. It “is an area that’s underserved and deserves more investment,” Heymach said. “It should be commensurate with the public health threat it represents.”



About the Author


Sharon Begley
Senior Writer, Science and Discovery (1956-2021)
Sharon covered science and discovery.

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Wildfire exposure decreases chances of survival for vulnerable cancer patients, study shows

Peer-Reviewed Publication

EMORY HEALTH SCIENCES

(ATLANTA) – People exposed to a wildfire within a year after having lung cancer surgery have significantly lower chances of survival compared to lung cancer patients who are not exposed to wildfires, researchers from Emory University, the American Cancer Society and Yale University found.

For the study, 499,912 individuals who underwent surgical removal of non-small cell lung cancer (NSCLC) between 2004-2019, were selected from the National Cancer Database. Of those individuals, 168,645 (36%) were exposed to wildfires within a year of being discharged from the hospital, according to ZIP-code level data from NASA’s Fire Information Resource Management System. 

The findings, published Thursday in the Journal of the American Medical Association (JAMA) Oncology, found those patients had worse overall survival than the other individuals in the study and that their chances of survival decreased the sooner the wildfire exposure occurred following their surgery. Individuals whose zip code overlapped with a wildfire event within three months of NSCLC surgery were 48% less likely to survive compared to patients not exposed to a wildfire event.  Patients exposed to wildfires 4-6 months (38%) and 7-12 months (17%) following surgery also had lower survival rates than unexposed patients.

“This study shows that the health impact of climate change-related extreme weather events such as wildfires is multi-faceted and further-reaching than we typically think,” says Yang Liu, PhD, chair and Gangarosa Distinguished Professor in Gangarosa Department of Environmental Health at Emory’s Rollins School of Public Health.

Satellite data provided by NASA, which also funded the study, enabled researchers to identify wildfire events globally and for an extended period.

“In addition to the health consequences of inhaling fire smoke, the interruption of care, anxiety due to property loss or financial hardship, as well as the mental trauma associated with experiencing a fire event can work together to negatively affect people’s health and well-being,” Liu adds. “The impact of smaller fires in the eastern U.S. also shouldn’t be ignored as they are often much closer to people.”

Lung cancer is the second most common cancer diagnosis in the United States and the leading cause of cancer-related deaths. Meanwhile, exposure to air pollution decreases the chance of lung cancer survival, and wildfire smoke is a major contributor to air pollution. 

“Surgery for lung cancer is a major operation with serious side effects and recovery takes months,” says Leticia Nogueira, PhD, scientific director of health services research at the American Cancer Society. “During recovery, individuals struggle with physical (diminished pulmonary and physical function, decreased mobility, increased fatigue), psychological (stress, anxiety, depression), and socioeconomic (out-of-pocket costs, ability to remain employed or maintain income levels, etc.) consequences of surgery, which can impact patients’ ability to prepare and respond to the threats posed by an approaching wildfire.”

However, air pollution was only one of several health threats — such as water and soil contaminations, increased stress and mental health issues, displacement and disruption to health care access – posed by wildfires that can negatively impact the long-term survival of individuals recovering from lung cancer surgery. 

“While wildfire smoke contributes to worsening air quality, which has been associated with increased cancer risk, proximity to wildfires poses several challenges that go beyond inhaling polluted air,” adds Nogueira. “These include the stress associated with the threat wildfires pose to property and life, the financial resources necessary to evacuate or shelter in place, and the health hazards associated with exposure to contaminated water and dust.  The additional challenges are especially concerning for cancer patients and survivors, who are already dealing with the physical, psychological, and socioeconomic consequences of cancer diagnosis and treatment.”

The researchers warn the health risks from wildfires will only intensify in the era of climate change.

“Climate change will result in reduced rainfall, higher temperature, and dryer soil in much of western North America, further exacerbating wildfire activity in the region,” Liu says. “We will see a longer fire season and more frequent, more intense fires.”

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JOURNAL

JAMA Oncology

DOI

10.1001/jamaoncol.2023.2144 

ARTICLE TITLE

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

Air pollution threatens health of a growing number of Americans

By Robin Foster, HealthDay News

In the American Lung Association's "State of the Air" report, released Wednesday, the number of people living with levels of air pollution that could jeopardize their health climbed from about 119 million in 2023 to 131 million now. File Photo by Terry Schmitt/UPI | License Photo

Nearly 40% of Americans live where the air is polluted enough to harm them, a new report warns.

In the American Lung Association's "State of the Air" report, released Wednesday, the number of people living with levels of air pollution that could jeopardize their health climbed from about 119 million in 2023 to 131 million now.

"We have seen impressive progress in cleaning up air pollution over the last 25 years, thanks in large part to the Clean Air Act. However, when we started this report, our team never imagined that 25 years in the future, more than 130 million people would still be breathing unhealthy air," Harold Wimmer, president and CEO of the American Lung Association (ALA), said in a news release announcing the findings.

"Climate change is causing more dangerous air pollution. Every day that there are unhealthy levels of ozone or particle pollution means that someone -- a child, grandparent, uncle or mother -- struggles to breathe," he said. "We must do more to ensure everyone has clean air."

Extreme heat, drought and wildfires have fueled recent rises in deadly air pollution, especially in the Western regions of the country, said report author Katherine Pruitt, senior director of the lung association's Nationwide Clean Air Policy.

"The air pollution produced by wildfire smoke is getting worse every year," Pruitt told CNN. "Climate change is contributing to that situation, and those wildfires are a very serious threat to our health."

While emissions of outdoor air pollutants have dropped 78% since the Clean Air Act was passed in 1970, "there still are way too many people breathing unhealthy air," Pruitt said.

In recent years, Pruitt noted she has seen a shift in air pollution becoming a growing problem in the West.

"Our cars are cleaner. Our fuels are cleaner. Most of the dirtiest coal-fired power plants have fortunately been shut down, and industry is cleaner. So that's cleaned up a lot of the traditional sources of pollution in the East, in the more industrial parts of the Upper Midwest and the Northeast," Pruitt said.

However, "the amount of oil and gas extraction that happens in the West has increased, which produces a lot of emissions," she said. "And they are suffering, first, from the impacts of climate change and wildfire. So a lot of that geographic shift you're seeing, particularly with particle pollution, is related to wildfire smoke."'

According to the new report, the 10 cities most polluted by year-round particle pollution were:Bakersfield, Calif.
Visalia, Calif.
Fresno-Madera-Hanford, Calif.
Eugene-Springfield, Ore.
San Jose-San Francisco-Oakland, Calif.
Los Angeles-Long Beach, Calif.
Sacramento-Roseville, Calif.
Medford-Grants Pass, Ore.
Phoenix-Mesa, Ariz.
Fairbanks, Alaska

Particle pollution, a mix of solid and liquid droplets so tiny they can infiltrate your body's defenses, is associated with an increased risk of death from heart disease, respiratory disease and lung cancer.

"Particle pollution is really deadly," Pruitt said. "We also see not only more people in more places affected, but the level of particle pollution that they're breathing is worse than it's ever been."

The new report also highlights how air pollution strikes minority communities the hardest.

While minorities make up about 42% of the U.S. population, they represent 52% of people living in a county with at least one failing grade for air pollution, the report found. In the counties with the worst air quality, 63% of the nearly 44 million residents there are minorities.

The findings show the United States still has "a huge air pollution issue" to tackle, said Dr. Lina Mu, an epidemiologist and associate professor at the University at Buffalo School of Public Health and Health Professions.

"Breathing the unhealthy air will cause tremendous health consequences, in particular for vulnerable populations such as pregnant women, fetuses, children and people with asthma or heart diseases. The impact on the next generation can be very profound," Mu told CNN.

"It will certainly need policies from multiple levels to reduce the emission of pollutants, adopt stronger regulations and standards, and address climate changes to be effective in controlling air pollution levels," she added.

More information

The National Institute of Environmental Health Sciences has more on air pollution.

Copyright © 2024 HealthDay. All rights reserved.

 

Climate change will give rise to more cancers

UCSF study focuses on global impact for major cancers and steps needed to lessen risks

UNIVERSITY OF CALIFORNIA - SAN FRANCISCO

Research News

 

Climate change will bring an acute toll worldwide, with rising temperatures, wildfires and poor air quality, accompanied by higher rates of cancer, especially lung, skin and gastrointestinal cancers, according to a new report from UC San Francisco.

In an analysis of nearly five dozen published scientific papers, the researchers provided a synopsis of future effects from global warming on major cancers, from environmental toxins to ultraviolet radiation, air pollution, infectious agents and disruptions in the food and water supply.

Ultimately, the most profound challenge to the global cancer picture could come from the disruption of the complex health care systems required for cancer diagnosis, treatment, and care, the authors wrote. The review appears in The Lancet Oncology.

"In the worldwide battle to mitigate climate change, the international community is not on track to slow emissions of greenhouses gases," said lead author Robert A. Hiatt, MD, PhD, UCSF professor of epidemiology and biostatistics, and associate director for population science at the UCSF Helen Diller Family Comprehensive Cancer Center. "2015-2019 were the five warmest years on record, and 2020 has seen tremendous climate impacts, from wildfires to hurricanes."

The impacts of climate change on health are large and are expected to continue growing without rapid action. High temperatures, poor air quality and wildfires cause higher rates of respiratory and cardiovascular diseases. Warmer temperatures and changing rainfall patterns raise the risk and spread of vector-borne disease, such as malaria and dengue. "Extreme weather events cause death, injury, displacement, and disrupt health-care delivery," the authors wrote.

Cancer is widely predicted to be the leading cause of death in the 21st century. Worldwide, there were 24.5 million new cases of cancer and 9.6 million deaths in 2017, a striking increase from 2008 with 12.7 million cases and 7.6 million deaths.

The authors said the biggest cancer threats are likely to be from air pollution, exposure to ultraviolent radiation and industrial toxins, and disruptions in food and water supply. Lung cancer, already the primary cause of cancer deaths worldwide, is expected to increase as a result of escalating exposure to particulate matter in air pollution, estimated to be responsible for as much as 15 percent of new cases.

While the overall effects of climate change on nutrition-related cancers are difficult to determine, the authors said, one comprehensive modeling study predicted more than half a million climate-related deaths worldwide, including cancer deaths, as a result of changes in food supply by 2050, such as reduced consumption of fruits and vegetables.

Climate change is already exacerbating social and economic inequities, leading to higher rates of migration and poverty. The authors note that poor people and communities of color are disproportionately affected by cancer and have a higher cancer mortality. World Bank estimates that climate change will push 100 million people globally back into poverty by 2030.

Major disruptions are also expected to take place in the infrastructure of health care systems for cancer control, which could affect all cancers. The COVID-19 pandemic has provided a clear example of this disruption, shifting medical resources away from cancer and causing thousands of patients to delay cancer screenings out of fear of contracting the virus.

"Extreme weather events such as storms and flooding can destroy or damage health-care infrastructure, reducing health care quality and availability," said the authors. These events also interrupt service delivery by causing power shortages, disrupting supply chains, transportation, and communication, and resulting in staff shortages. Ironically, COVID-19 also revealed a ray of hope in reversing the damage.

"The early pandemic response resulted in a striking reduction in air pollution," Hiatt said, "showing the potential of extreme measures to result in rapid environmental change."

It could take decades to fully understand the impact of climate change on cancer, given a sometimes lengthy delay from exposure to clinical diagnosis. But the authors said that shouldn't prevent acting now, as the harmful impacts from air pollution and other climate risks will continue to grow during that time.

"There is a lot we can be doing to mitigate climate change and to mitigate the impact on cancer," said co-author Naomi Beyeler, MPH, co-director of the Evidence to Policy Initiative and Lead for Climate and Health at the UCSF Institute for Global Health Sciences. "We should be doing both, and we should be doing both with urgency."

By reducing pollution, deaths from lung cancer could decline, the authors said, and there are numerous clinical, behavioral, and policy solutions to slow climate change, and prevent cancer cases and deaths.

"The COVID-19 pandemic has shown us the importance of science and public health," said Beyeler, "and we have seen over the past months that as a global health community, we are able to mobilize the investments, research, and collective action needed to solve health problems on a global scale. Now is the time to apply this ambition to tackling the climate crisis."

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About UCSF:

The University of California, San Francisco (UCSF) is exclusively focused on the health sciences and is dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care. UCSF Health, which serves as UCSF's primary academic medical center, includes top-ranked specialty hospitals and other clinical programs, and has affiliations throughout the Bay Area. Learn more at ucsf.edu, or see our Fact Sheet.