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Lung Cancer in Nonsmoking Individuals: Differences in Genetics and Response to Treatment


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Lung cancer in nonsmokers is a diverse and distinct disease from lung cancer in smokers and is likely to respond differently to targeted treatments, according to results from a new study published by Chen et al in the journal Cell.

Scientists studied a patient population in Taiwan with high rates of lung cancer among nonsmokers and found a range of genetic changes which varied depending on a patient’s age or sex. Many nonsmokers with lung cancer had signs of DNA damage from environmental carcinogens, and young women in particular had genetic changes that are known to drive cancer.

Study Methods

Scientists at The Institute of Cancer Research, London, worked with colleagues at the Academia Sinica and the National Taiwan University to analyze tumor samples from 103 patients with lung cancer from Taiwan, the majority of whom were nonsmokers. The researchers conducted a detailed analysis of genetic changes, gene activation, protein activity, and cellular “switches” in lung cancer to develop a comprehensive overview of the biology of the disease in nonsmokers.

Findings

Looking at the genetics and the related proteins produced by cancer cells in the tumor samples, scientists found that some early-stage lung tumors in nonsmokers were biologically similar to more advanced tumors in smokers. 

Tumors in women often had a mutation in the EGFR gene, whereas in men, the most common faults were in the KRAS and APC genes. The study also found a pattern of genetic changes involving the APOBEC gene family in three-quarters of tumors from female patients younger than 60, and in all women without mutations in the EGFR gene.

The team also picked out groups of patients—particularly among older women—whose cancers had mutation patterns linked to cancer-causing substances in their environment, such as pollutants.

Finally, the team identified 65 proteins that were overactive in lung tumors that matched with existing candidate drugs. They found that one protein that cuts away at the surrounding tissue, called MMP11, was linked to poorer survival and could potentially be explored as a marker for early detection.

Commentary

While the new study looked at patients treated in Taiwan, the researchers believe that many of their findings could be applicable to patients globally. Next, they will be validating their findings in larger studies and beyond Asia.


“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 nonsmokers, and found that their disease is molecularly diverse and distinct from what we classically see in smokers."
— Jyoti Choudhary, PhD

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Study coauthor Jyoti Choudhary, PhD, Team Leader in Functional Proteomics at The Institute of Cancer Research, 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 nonsmokers, 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 nonsmokers 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.”

She concluded: “Some early-stage lung tumors 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.”

Disclosure: For full disclosures of the study authors, visit cell.com.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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