More than 190,000 global cases of lung adenocarcinoma were linked to air pollution in 2022. Increasingly, this deadly disease is affecting people who have never smoked. Among them are thousands of women, younger individuals and residents of highly polluted regions. New research reveals a complex interplay of factors behind this shift.
Here are key insights into the changing face of lung cancer:
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Up to 20% of lung cancer cases now occur in people who have never smoked
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Outdoor air pollution is the second biggest cause after smoking
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Women, especially in Asia, are disproportionately affected
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Genetic mutations such as EGFR are key drivers
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Targeted therapies have extended survival in many cases
Martha’s case and a changing reality
Martha was 59 when her persistent cough and thick mucus led doctors to finally request an X-ray. It revealed a shadow in her lung. After further tests, including bronchoscopy and tissue biopsy, she was diagnosed with Stage IIIA adenocarcinoma. Although she occasionally smoked socially, Martha did not identify as a smoker. Her cancer had spread to the lymph nodes but not to distant organs.
She later tested positive for an EGFR mutation – a genetic alteration strongly associated with lung cancer in never-smokers. Since then, she has been on targeted therapy and has lived with the disease for nearly three years. Despite serious side effects such as fatigue and muscle pain, the treatment is keeping her cancer under control.
Andreas Wicki and lung cancer in non-smokers
Different biology and patient profile
According to oncologist Andreas Wicki of the University Hospital in Zurich, lung cancer in non-smokers is now recognized as a separate clinical entity. The molecular profile of these tumours differs significantly from smoking-related cancers. Key differences include:
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Higher prevalence of adenocarcinoma
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More frequent EGFR mutations
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Increased occurrence among women and younger individuals
Wicki notes that non-smokers under 40 who develop lung cancer are almost always diagnosed with adenocarcinoma, not squamous cell carcinoma, which dominated earlier in the 20th century.
Delayed diagnosis and symptom misattribution
Adenocarcinoma often goes undetected until it has reached an advanced stage. The initial symptoms – such as coughing, chest pain, and wheezing – are vague and frequently attributed to benign causes. Because of the historical link between smoking and lung cancer, doctors and patients may overlook the possibility of cancer in never-smokers.
Genetic mutations and targeted drugs
Non-smoker lung cancers often harbour specific "driver mutations" – genetic changes that promote uncontrolled cell growth. Among the most common is EGFR, a gene coding for a cell-surface protein involved in cell division.
Drugs targeting EGFR first became available in the early 2000s. Initially very effective, they often failed due to resistance development. More recent therapies, however, have improved dramatically.
“The median survival for patients with driver mutations has risen from less than 12 months to several years,” says Wicki. Some patients have lived more than a decade on targeted drugs.
Francis Crick Institute and the link to air pollution
PM2.5 exposure and cell activation
At the Francis Crick Institute in London, researchers have explored how air pollution may trigger tumour growth in non-smokers carrying EGFR mutations. Their 2023 study found that tiny airborne particles (PM2.5) do not directly damage DNA like cigarette smoke, but instead reawaken dormant cells that carry cancer-causing mutations.
Postdoctoral researcher William Hill explains that macrophages, immune cells in the lungs, absorb these particles and release cytokines. These chemical signals can cause pre-mutated cells to start multiplying, potentially leading to cancer.
Global burden of air pollution
A study by the International Agency for Research on Cancer (IARC) attributed approximately 194,000 cases of lung adenocarcinoma in 2022 to PM2.5 pollution. The highest concentrations were observed in East Asia, especially China.
Here's a summary of the estimated global burden of pollution-related adenocarcinoma:
| Region | Estimated cases (2022) | Notable features |
|---|---|---|
| East Asia | >90,000 | High PM2.5 levels, especially in China |
| South Asia (e.g., India) | Rising rapidly | Delhi exceeds WHO limits by 20x |
| Europe | ~30,000 | Improved air standards, but legacy impact |
| North America | ~20,000 | Wildfire-linked PM2.5 exposure increasing |
| Rest of the World | ~50,000 | Indoor pollution from wood/coal stoves |
Gender differences and hormonal influence
Women are at particular risk. Female non-smokers are more than twice as likely as their male counterparts to develop lung cancer. Asian women are even more vulnerable, with studies indicating higher frequencies of EGFR mutations.
Hormonal factors may contribute. Certain genetic variants affecting oestrogen metabolism are more common among East Asians, potentially explaining their susceptibility. However, further research is needed to fully understand these patterns.
Environmental factors and shifting strategies
Indoor and outdoor pollution
Multiple environmental factors besides cigarette smoke contribute to lung cancer in non-smokers:
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Radon gas – a naturally occurring radioactive gas seeping into buildings
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Second-hand smoke – exposure at home, work or public spaces
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Cooking fumes – especially from oil-based frying in poorly ventilated homes
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Burning wood or coal indoors – common in developing regions
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Outdoor air pollution – vehicle exhaust, industrial emissions, wildfires
Outdoor air pollution is now recognized as the second leading cause of lung cancer globally. PM2.5 levels remain dangerously high in many urban areas despite efforts to reduce emissions.
Policy shifts and new health guidelines
In 2021, the World Health Organization (WHO) updated its air quality guidelines for PM2.5, halving the permissible annual average. Despite this, 99% of the global population still lives in areas where PM2.5 exceeds these new limits, according to Ganfeng Luo of IARC.
The full impact of improving air quality may not be seen for decades. Christine Berg, a retired oncologist from the US National Cancer Institute, warns that changes in exposure can take 15 to 20 years to reflect in cancer statistics.
Nonetheless, the growing threat of wildfires, driven by climate change, may undo progress in many regions. A recent study has linked wildfire smoke exposure with increased lung cancer risk.
Toward a new public image of lung cancer
Although the disease remains closely associated with smoking, that perception may be outdated. The growing share of never-smokers among lung cancer patients is altering the demographic and social understanding of the disease.
Martha, for example, continues treatment with an EGFR inhibitor, balancing quality of life with side effects. “It’s definitely not a vitamin pill,” she says. But she is alive and stable nearly three years after diagnosis.
The fatalistic view of lung cancer is changing, thanks to better treatments and deeper insights into environmental and genetic causes. Future prevention efforts must look beyond tobacco – to air, homes and genes.
Source: BBC