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Lung cancer cell - image courtesy of the LRI EM unit

This entry is part 12 of 12 in the series Science Surgery

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.

Types of lung cancer

Lung cancer is divided into 2 main groups:

  • small cell lung cancer, and
  • non small cell lung cancer.

They behave in different ways and respond to treatment differently. Around 9 in 10 lung cancers are non small cell lung cancer.

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. 

Comments

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Pinki November 23, 2018

Because I smoke next to them

Tim Garvey November 23, 2018

My dad died of lung cancer. I’m the only one out of 6 that has never smoked. Unfortunately I’m the only one left, have always wondered will I get cancer.

Sergii November 23, 2018

Non–small cell lung cancer (NSCLC), which accounts for around 85% of lung cancer cases, has historically been considered a nonimmunogenic disease; however, recent data show that much of this lack of immune responsiveness is functional rather than structural (ie, possible to overcome therapeutically).

This will allow immunotherapeutic strategies to shift the balance of immune activity away from a tumor-induced immune-suppressive state toward an active antitumor immune response.

Immune responses develop quickly, and are mediated by various effector cells NK cells, polymorphonuclear leukocytes, and mast cells, as well as antigen-presenting cells [APCs] such as macrophages and dendritic cells [DCs]), which lead to the secretion of interferon gamma (IFN-γ) and perforin, as well as cytokines, that induce apoptosis of tumor cells.

Thus, the most effective is not only lifestyle (quitting smoking), but preventive targeting immunotherapy.
1. Aimed at reducing the overexpression of pro-inflammatory cytokines
2. Activation of the cytotoxic potential of lymphocytes
3. Formation of antigen-presenting cells
4. Unlocking “Immune Checkpoints”

Carol scott November 23, 2018

I would also like to know why most smokers don’t get lung cancer? It would be interesting to know if they have some gene that protects them that could help others. Unfortunately most doctors are so convinced smoking causes lung cancer that few are looking at anything else.

Jim Kendall November 22, 2018

Complicated

Isla November 21, 2018

When I was 3 I got diagnosed with stage 4 lung cancer. My parents never smoked nor did any other family members. At the time there wasn’t much research on the type of cancer I had, however they believed that I was born with a faulty gene which developed into my tumour. I and now 19 and 16 years clear of cancer!!

Nayan November 21, 2018

My father had never smoked nor drank alcohol and was never surrounded by smokers. He developed a persistent cough and so eventually had a scan. He had stage 4 sarcomatoid lung cancer. He lived 1 month and passed away. There’s just not enough people to study for research to progress which is a shame.

amanda November 19, 2018

Because they are unlucky and cancer doesn’t “pick” it’s sufferers