Science Surgery: ‘Why do never-smokers get lung cancer?’

Lung cancer cell - image courtesy of the LRI EM unit

Our Science Surgery series answers your cancer science questions.

Janette asked: “Why do never-smokers get lung cancer?”

“It’s a question that often comes up in the clinic,” says Dr Mariam Jamal-Hanjani, an oncologist and clinical researcher specialising in lung cancer at University College London. “And it’s one that researchers have been asking for decades.”

The link between smoking and lung cancer has been known for almost 70 years. It’s the biggest cause of lung cancer in the UK, with around 7 in 10 lung cancers caused by smoking cigarettes. But there’s also a group of people who develop lung cancer and have never lit a cigarette.

“Around 10-15% of the lung cancer patients I see have never smoked,” says Jamal-Hanjani, who’s working on two Cancer Research UK-funded studies. “But we don’t always know why it is that these people get lung cancer.”

According to Jamal-Hanjani, the data suggests that genetics play a role, as well as environmental or occupational exposures.

Spotting DNA differences

When you compare lung cancers in smokers and never-smokers, differences start to emerge. The first of which is the types of lung cancer they develop.

“Smokers can develop all types of lung cancers, although the association is stronger for small cell lung cancer and squamous cell carcinoma, whereas never-smokers are more likely to develop a non small cell lung cancer called lung adenocarcinoma,” says Jamal-Hanjani.

There are also differences when you look at the DNA inside the tumour cells.

Non-smokers who develop lung cancer are more likely to have cells with a fault in a gene called EGFR. This fault is commonly found in Asian women who had never smoked and developed lung cancer. But according to Jamal-Hanjani, it’s seen in other people too.

“If you’ve never smoked you’re more likely to have a lung cancer that’s driven by a fault in one or potentially more genes,” she says. “And these aren’t necessarily genetic faults that you’re born with, they’re faults that develop during someone’s lifetime.”

These DNA faults can offer up new options for treatment. For example, changes in the EGFR gene can be targeted by drugs like elortinib (Tarceva) and gefitinib (Iressa).

Looking for environmental risks

To understand what might increase someone’s risk of cancer, researchers study large groups of people for many years to look for links between exposure to something and lung cancer.

“These are really tough studies because they need to involve big numbers of people and long periods of follow up. And you need to clearly demonstrate that people who were exposed to something develop cancer, and that there are no other factors that could explain the association.”

To make it easier to exclude other risk factors, scientists will often run ‘case controlled’ studies.

“You might have one person who was exposed to second hand smoke, and then you’ll have another patient within the study who’s matched to that person in every way other than the fact they weren’t exposed to second hand smoke,” says Jamal-Hanjani. “And then you look in big numbers to see if the group of patients who were exposed to smoke were more likely to develop lung cancer.”

Studies like this have shown that being exposed to second hand smoke, for example by living with someone who smokes, can increase a person’s risk of lung cancer by almost a third.

Researchers have also discovered that exposure to asbestos, radon gas or tiny particles that come from diesel exhausts and construction sites can increase someone’s risk of lung cancer. But the individual risks are small.

Staying vigilant

Overall, the risk of developing lung cancer if you’ve never smoked is far lower than if you have or still do. But Jamal-Hanjani says that this shouldn’t lead to a blind sense of security.

“I’ve had patients who had a persistent cough or who were coughing up blood, but believed that because they had never smoked they couldn’t possibly have lung cancer. And it’s not true. There’s still a chance they could develop lung cancer and it not have anything to do with cigarettes. So, people should always seek advice from their doctor if they notice any changes.”

Katie

We’d like to thank Janette for asking this question. If you’d like to ask us something, post a comment below or email sciencesurgery@cancer.org.uk with your question and first name. 

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