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Why women who never smoked cigarettes are getting cancer now more frequently

Q: Why is it that someone can smoke for 20 years without getting cancer; while someone who has never smoked can be diagnosed with lung cancer?

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People ask me this question very frequently.

Because recent research reports (1) say women who never smoked cigarettes are getting cancer now more frequently. The findings, published in The Lancet Respiratory Medicine, reveal that lung adenocarcinoma, the most common type of lung cancer among non-smokers, accounts for nearly 60% of lung cancer cases in women compared to 45% in men.

The study suggests that environmental factors, particularly air pollution, along with genetic predisposition and immune responses, may be driving this rise in non-smoking-related lung cancer.

One of the most significant risk factors for lung cancer in non-smokers is genetic mutations, especially mutations in the EGFR gene. This gene provides instructions for producing a protein on the surface of cells involved in growth and division.Mutations in this gene drive uncontrolled cell division and tumour growth. They are found in 50% of lung adenocarcinomas in non-smoking Asian women and 19% in non-smoking western women – compared with 10–20% in non-smoking men. (2)

However, rising exposure to air pollution, which is known to trigger EGFR mutations – may also be contributing to their increasing prevalence.

Other genetic changes that drive tumour growth include mutations in the genes ALK and ROS1, which are found in about 5% of lung cancer cases in non-smokers. These mutations are more often seen in younger non-smoking women, particularly in Asia. (3). Thankfully, improved screening programmes, especially in east Asian countries, have helped detect these mutations more frequently.

Mutations in TP53, a crucial tumour-suppressing gene, also appear to be more commonly found in non-smoking women than in men. This gene prevents cells from becoming cancerous, and its mutation leads to out-of-control cell growth. The hormone oestrogen can interact with TP53 mutations, making lung cancer more likely to develop in women over time.

Another gene that is worth mentioning is KRAS. Mutations in this gene are usually associated with smoking-related lung cancer, however, they are increasingly being found in non-smokers – particularly women. (4)

Recent studies suggest that exposure to tiny particles in the air, or PM2.5 (so-called because they are 2.5 micrometres or smaller) may be responsible for these mutations in non-smoker women.

Since PM2.5 levels continue to rise in many towns and cities, exposure to these particles could be another factor not only in lung cancer but also in other types of cancers in women.

In addition to genetic predisposition, hormone fluctuations may influence tumour growth in women. Oestrogen receptors are found in lung tissue, and experimental studies suggest that oestrogen promotes tumour growth. Studies have shown.) (5) that women who receive hormone-replacement therapy (HRT), have a lower risk of lung cancer compared with women not on HRT, suggesting that natural oestrogen cycles may provide some level of protection.

Beyond genetics and hormones, chronic inflammation could also explain why lung cancer is rising among non-smoking women. Women are more likely to develop autoimmune diseases than men, and problems with the immune system can play a role in cancer. Persistent inflammation can cause repeated damage to tissues, leading to changes in DNA and promote abnormal cell growth, all of which raise the risk of cancer. (6)

Small airways may cause more fine particles to become trapped in women’s lungs compared to men.

Additionally, oestrogen has been shown to amplify inflammatory responses when exposed to pollutants, potentially making lung tissue more prone to damage that can lead to lung cancer.

Women are more exposed to air pollution as they spend more time indoors where toxic fumes from cooking and heating are more common.

Air pollution in the home, especially from things like wood, coal and kerosene, can raise the risk of lung cancer. Women working in places such as textile factories, beauty salons and hospitals are also more exposed to harmful chemicals that can damage the lungs.

Recent research suggests that HPV infection is becoming a significant factor too. (7)

And finally secondhand smoke is one of the causes too: It is smoke from burning tobacco products and the smoke exhaled by smokers (fathers, husbands, sons, brothers). It's also known as environmental tobacco smoke, involuntary smoke, or passive smoke.

All the above factors are contributing to increase in lung cancer incidents in non-smoking women.

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