Lung Cancer in Nonsmokers? Study Identifies Air Pollution as a Trigger

The cough just wouldn’t go away.

For weeks, Molly Campbell had an intermittent dry, hacking cough that she could not shake. After a pair of doctor visits, she was prescribed steroids and an inhaler. Nothing worked. Then, about three months in, she started coughing up blood.

Campbell was given a CT scan. The result? Two large masses and hundreds of small nodules in both lungs.

“They said it’s not likely it’s cancer,” recalled Campbell, who is 29 and lives in rural Virginia. “They’re like, it’s basically no way because you’re so young and you don’t smoke and all this other stuff.”

The diagnosis left Campbell numb: adenocarcinoma. Stage 4 lung cancer.

Experts say that 10 to 20 percent of lung cancer patients in the United States are so-called “never smokers” like Campbell, and they have struggled to understand how otherwise healthy people can suddenly find themselves diagnosed with the most severe forms of the disease.

A new study, however, suggests a culprit: the polluted air that healthy people breathe.

A British research team says it has identified a mechanism in which airborne particulate matter may trigger some forms of lung cancer in otherwise healthy people who have never smoked.

The team’s findings, which scholars are currently reviewing for publication, suggest that airborne pollutants commonly found in vehicle exhaust and in the smoke given off by fossil fuels can promote cancers in patients who have a mutated form of a gene known as epidermal growth factor receptor, or EGFR. Mutations to the EGFR gene were found in about half of the patients with lung cancer who have never smoked.

“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,” said Charles Swanton, the lead researcher, in a news release. “The risk of lung cancer from air pollution is lower than from smoking, but we have no control over what we all breathe.”

Swanton presented the results this month at a symposium of the European Society for Medical Oncology in Paris.

A clinician scientist at the Francis Crick Institute and University College London, Swanton said his team had wondered whether air pollution could promote the growth of tissue that has mutations and causes lung cancer. The cancer mutations are found in normal tissue, he notes—appearing in about one in two biopsies—and they increase as a result of aging.

Then there is the air pollution factor. As part of the study, Swanton and his team tried to figure out whether PM2.5, tiny particles that are about 3 percent of the width of a human hair, could cause inflammation in the lungs and lead to cancer, according to the Francis Crick Institute. 

Researchers examined data from 400,000 people in South Korea, Taiwan and the United Kingdom, comparing the levels of PM2.5 pollution and the rates of EGFR mutant lung cancer. They found higher rates of EGFR lung cancer as well as other types of cancer in people living where there were higher levels of pollution, the institute said in a statement.

Then the team turned to mice. In lab experiments, researchers found that when mice carrying cells with the EGFR mutation were exposed to air pollution, cancers were more likely to start from those cells, Swanton said.

Swanton said that when pollution enters into a person’s airway, cells in the lung release a type of protein known as interleukin-1β in an inflammatory response. Blocking the release of this protein prevents cancer from forming, the study showed. 

The team hopes its study will prove useful in treating early-stage cancers in which environmental triggers awaken cells carrying cancer-causing mutations in different parts of the body, the Francis Crick Institute said.

Swanton describes PM2.5 as a “silent killer.” 

“PM2.5 contributes to 8 million deaths a year, which is as many as tobacco,” he said in an interview. “So it is a big problem.” 

It “took a while to put the pieces of the puzzle together,” Swanton added, but after 10 years of research, a picture started taking shape over the last six months. “It’s honestly been like a eureka period,” he said. “It’s like ‘wow.’ The implications are massive, I think, for how cancer is formed.’’ 

In his understanding of how cancer is formed, Swanton said he was influenced by the work of  Allan Balmain, a professor of cancer genetics at the University of California, San Francisco, who began studying mutations, cancer and environmental carcinogens in the 1980s. Balmain said he believes that Swanton’s work will increase awareness of the importance of carcinogenesis, or how normal cells become cancer cells.

“The whole field of cancer genetics has been focused on the mutation,” Balmain said. “What we know is that the mutations are there in our normal cells. All of us have hundreds or thousands of mutations. Sometimes you can have thousands of mutations in a single cell. And these mutated cells are sitting there like a time bomb waiting to go off. And it’s only when you get exposed to the promoters,” like fine particulates, “that these initiated cells, these mutated cells, start to grow.”

What Swanton has demonstrated, he said, is that those cells are already in the lungs, and that when people breathe in air pollution, the fine particles stick to the lungs and cause tissue damage. The tissue tries to repair that damage and eventually succeeds. But if that damage occurred in a cell that already has a mutation, “then this really leads to the development of the disease, the very first signs of a tumor beginning to grow,” he said.

For Molly Campbell, who is undergoing chemotherapy treatment every three weeks, it was a thoracic surgeon who finally confirmed that she had lung cancer, in March. He has 30 years of experience, and before her biopsy he had told her that “if you held a gun to my head and said, ‘What is this?,’ the last thing I would say is cancer.”

But after two biopsies, it was what she feared the most. And she wonders how she got lung cancer: Could air pollution, which not only causes climate change but is aggravated by it, be to blame?

“I 100 percent believe that it has a lot to do with our health, whether it be cancer or any kind of illness,” she said of climate change. “But there’s so many environmental pollutants out there these days that probably aren’t even regulated.”

Campbell is now preparing her 8-year-old son for her death. When she talks to him, she asks him to remember the family vacations and the times they played together. He asks her if, when she goes to heaven, can she come down and see him?

She also wonders about the broader future. Will climate change ever be effectively addressed by policymakers? “I think it’s going to be several generations,” Campbell said.

Like so many other scientists and health advocates, Swanton believes it is urgent that PM2.5 levels around the world be lowered. He noted that 99 percent of the world’s population lives in areas where levels exceed what is deemed safe by the World Health Organization.

“Five times more people are exposed to pollution than tobacco, so it becomes more of an issue,” Swanton said. “And PM2.5 is causing diseases other than cancer,” he noted, from dementia to cardiovascular disease.

“Climate and human health are intimately linked. And this is just one out of over 100 other environmental carcinogens that may not cause DNA mutations,” said Swanton, adding that he found no evidence of a carcinogenic signature in DNA from lung cancers in nonsmokers. “So what are the other 99 doing? We need to know.”