The number of lung cancer cases in people who have never smoked is increasing. The disease is different from lung cancer caused by smoking, so what causes it?

Martha first realised that something was wrong when her cough changed and the mucus in her airways became increasingly viscous. Her doctors put it down to a rare disorder she had that caused her lungs to become chronically inflamed. "No worry, it must be that," she was told.

When she finally had an X-ray, a shadow was detected on her lung. "That set the ball rolling," Martha recalls. "First, a CT scan was done, then a bronchoscopy [a procedure that involves using a long tube to inspect the airways in a person's lungs] to take tissue samples." After the tumour was removed, about four months after she'd first reported symptoms to her GP, she received the diagnosis: Stage IIIA lung cancer. The tumour had infiltrated the surrounding lymph nodes but had not yet spread to distant organs. Martha was 59 years old.

"It was a total shock," says Martha. Although she would occasionally light up a cigarette at a party, she never considered herself a smoker.

Lung cancer is the most common cancer worldwide and the leading cause of cancer death. In 2022, about 2.5 million people were diagnosed with the disease and more than 1.8 million died. Although tobacco-related lung cancers still account for the majority of diagnoses worldwide, smoking rates have been declining for several decades. As the number of smokers continues to fall in many countries around the world, the proportion of lung cancer occurring in people who have never smoked is on the rise. Between 10 and 20% of lung cancer diagnoses are now made in individuals who have never smoked.

"Lung cancer in never-smokers is emerging as a separate disease entity with distinct molecular characteristics that directly impact treatment decisions and outcomes," says Andreas Wicki, an oncologist at the University Hospital Zurich, Switzerland. While the average age at diagnosis is similar to that of smoking-related lung cancers, younger patients with lung cancer are more likely to have never smoked. "When we see 30- or 35-year-olds with lung cancer, they are usually never-smokers," he says.

Another difference is the type of cancer being diagnosed. Until the 1950s and 1960s, the most common form of lung cancer was squamous cell carcinoma – a type which begins with the cells that line the lungs. In contrast, lung cancer in never-smokers is almost exclusively adenocarcinoma – a type which starts in mucus-producing cells – which is now the most common form of lung cancer in both smokers and never-smokers.

Like other forms of lung cancer, adenocarcinoma is usually diagnosed at an advanced stage. "If there's a 1cm (0.4in) tumour hidden somewhere in your lungs, you won't notice it," says Wicki. The early symptoms, which include persistent coughing, chest pain, shortness of breath or wheezing, often only appear when the tumour is larger or has spread. In addition, the historically strong link between smoking and lung cancer may inadvertently lead non-smokers to attribute symptoms to other causes, says Wicki. "Most cases in never-smokers are therefore only diagnosed at stage 3 or 4."

Lung cancer in never-smokers is also more common in women. Women who have never smoked are more than twice as likely to develop lung cancer as male never-smokers. Aside from lung anatomy and environmental exposures, at least part........

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