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Lung cancer in non-smokers ‘biologically distinct’ from that in smokers – study

By Nilima Marshall
Lung cancer in non-smokers is a biologically distinct disease from that in smokers, research suggests.

Scientists at the Institute of Cancer Research (ICR) in London say that many patients who had the disease but did not smoke showed signs of DNA damage from cancer-causing substances that are present in the environment, such as vehicle exhaust fumes.

These genetic changes were found to vary depending on a patient’s age or sex.

The researchers believe that the findings, published in the journal Cell, could pave the way for tailored treatments based on newly identified genetic changes.

ICR chief executive Professor Paul Workman said: “This new study offers a deep dive into the biology of lung cancer in people who have never smoked.

“It reveals new ways of telling apart patients with different tumour characteristics that could be exploited with tailored treatment strategies.”

Most recent figures indicate that around 6,000 people who have never smoked die of lung cancer in the UK every year, which accounts for nearly a sixth of the total deaths from the disease.

The researchers say the proportion of lung cancers that occur in non-smokers is much higher in East Asian countries such as Taiwan, especially among women.

So a team of scientists at the ICR worked alongside colleagues in East Asia to analyse tumour samples from 103 patients in Taiwan who had the disease and did not smoke.

Genetic and protein analysis revealed that some early-stage lung tumours in non-smokers had molecular features which were similar to more advanced disease in smokers.

The team also found mutations in a gene, known as EGFR, to play a role in the development of lung cancer in women, while the most common faults in men with the disease were in the KRAS and APC genes.

According to the researchers, these differences could affect the response to targeted drugs in men and women.

Three-quarters of tumours from female patients under the age of 60 showed a pattern of genetic changes involving a gene family, known as APOBEC.

According to the team, these patterns were seen in all women who did not have faults in the EGFR gene.

The researchers said that patients without EGFR faults tend to respond better to immunotherapy, so prior tests could help determine which women are more likely to respond to this form of treatment.

As part of the next steps, the researchers are seeking to validate their findings with larger studies beyond Asia.

Study author Dr Jyoti Choudhary, team leader in functional proteomics at the ICR in London, said: “We carried out the most comprehensive study ever conducted into the biology of lung cancers in an East Asian population with a high proportion of non-smokers, and found that their disease is molecularly diverse, and distinct from what we classically see in smokers.

“We found distinct patterns of genetic faults in non-smokers and between women and men, which suggest that a woman who has never smoked, for example, is likely to respond differently to treatment than a male smoker.

“Some early-stage lung tumours had molecular features that are much more like that typically seen in later-stage disease – which could help us more accurately diagnose patients with aggressive disease, and inform treatment strategies.”

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