Lung Cancer in Nonsmoking Individuals: A Review

Our plain-English summary of Lung Cancer in Nonsmoking Individuals: A Review, by C. Murphy, T. Pandya, C. Swanton, et al (JAMA, 2025).

The study

• Authors: C. Murphy, T. Pandya, C. Swanton, B.J. Solomon
• Journal: JAMA
• Published: 2025;334(20):1836-1845
• Type of article: Review
• Cited by: 34 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Importance: Lung cancer in nonsmoking individuals (defined as people who have smoked fewer than 100 cigarettes in their lifetime) accounts for 15% to 20% of all lung cancer cases worldwide. In the US, the annual incidence of lung cancer in nonsmoking individuals is 14.4 to 20.8 per 100 000 person-years in females and 4.8 to 12.7 per 100 000 person-years in males.

Observations: Most lung cancers in nonsmoking individuals are histologically adenocarcinomas (60%-80%) with the remainder being squamous or adenosquamous (10%-20%) and rarely small cell lung cancer (<10%). Risk factors include exposure to passive smoking, radon exposure, air pollution, asbestos, and history of lung cancer in a first-degree family member. Therapeutically targetable genomic variants, such as EGFR mutations or ALK gene rearrangements, are more common in tumors from nonsmoking individuals compared with those with a smoking history (defined as people who currently or formerly smoked) (43% vs 11% for EGFR and 12% vs 2% for ALK). In contrast, tumor mutation burden, the number of somatic mutations in a tumor cell, is lower in lung cancer among nonsmoking individuals (0-3 mutations/megabase [Mb] vs 0-30 mutations/Mb). Similar to individuals with a history of smoking, nonsmoking individuals with lung cancer may present with wheeze, chest pain, dyspnea, hemoptysis, or symptoms attributable to metastatic disease (eg, bone pain and headache) or be diagnosed with incidentally detected disease. The US Preventive Services Task Force does not currently recommend lung cancer screening with low-dose computed tomographic scans for nonsmoking individuals, although screening guidelines vary globally. Treatment typically involves a combination of surgery, radiotherapy, and systemic therapies depending on stage, performance status, and molecular features of the tumor. Comprehensive next-generation sequencing should be performed on stage Ib to IIIa lung cancer tumor tissue from nonsmoking individuals because actionable genomic alterations, such as EGFR mutations or ALK gene rearrangements, are treated with targeted therapy such as the tyrosine kinase inhibitors osimertinib or lorlatinib, respectively. Median survival among nonsmoking individuals with advanced non-small cell lung cancer (stage IIIb or higher) and actionable genomic alterations can exceed 3 to 5 years, while survival without these genomic alterations is similar to lung cancer in people with a history of smoking (1-2 years).

Conclusions: Lung cancer in nonsmoking individuals accounts for 15% to 20% of lung cancer cases worldwide. Among patients with lung cancer, nonsmoking individuals are more likely to have genomic alterations such as EGFR mutations or ALK gene rearrangements, and these patients have improved survival when treated with tyrosine kinase inhibitors compared with chemotherapy.

In plain English

This article was a review, not a new study. The authors searched PubMed for English-language articles on lung cancer in non-smokers (people who had smoked fewer than 100 cigarettes in their lifetime) from January 2005 to August 2025, and included 92 of the 902 studies retrieved. In its abstract and introduction the review said lung cancer in non-smokers made up 15% to 25% of lung cancer worldwide; its conclusions gave 15-20%. Most such cancers (60-80%) were adenocarcinomas. Asbestos was listed as a risk factor with an attributable fraction of 8%, and was described as an IARC Group 1 carcinogen. The review gave no detail on asbestos fiber types or exposure levels. EGFR variants were found in 43% of tumors from non-smokers versus 11% from people with a smoking history, and ALK rearrangements in 12% versus 2%. The authors concluded that non-smokers with lung cancer are more likely to have these alterations, and that such patients have improved survival with tyrosine kinase inhibitors compared with chemotherapy. The authors noted that they did not formally evaluate the quality of the evidence.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Narrative review of published studies on lung cancer in non-smokers, based on a PubMed search; 92 of 902 retrieved studies were included
• Who was studied: Published English-language studies on lung cancer in non-smokers (defined as people who have smoked fewer than 100 cigarettes in their lifetime), searched from January 1, 2005 to August 1, 2025
• Exposure: Risk factors for lung cancer in non-smokers reviewed: passive smoking, radon, air pollution, asbestos, silica, prior chest radiotherapy, and family history. Asbestos is mentioned only in general terms, with no fiber type, product, job or dose specified.
• Main results:
  • Lung cancer in non-smokers was described as accounting for 15-25% of all lung cancer in the abstract and introduction, and 15-20% of cases worldwide in the conclusions
  • Percentage attributable fractions given for lung cancer in non-smokers: passive smoking 15%, radon 9%, air pollution 8%, asbestos 8%, family history of lung cancer in a first-degree relative 26%
  • Adenocarcinomas made up 60-80% of lung cancers in non-smokers, compared with 40% among current or former smokers with lung cancer
  • EGFR variants were found in 43% of tumors from non-smokers vs 11% from those with a smoking history; ALK rearrangements were found in 12% vs 2%
  • Tumor mutation burden was lower in lung cancer among non-smokers (0-3 mutations per megabase) than in smokers (0-30 mutations per megabase)
  • Among non-smokers with advanced non-small cell lung cancer (stage IIIb or higher), median survival can exceed 3-5 years with actionable genomic alterations; without them, survival is similar to lung cancer in smokers (1-2 years)
  • The US Preventive Services Task Force does not currently recommend low-dose CT lung cancer screening for non-smokers; screening guidelines vary globally
• The authors' conclusion: The authors concluded that lung cancer in non-smokers accounts for 15-20% of lung cancer cases worldwide. They concluded that non-smokers with lung cancer are more likely to have genomic alterations such as EGFR variants or ALK rearrangements, and that these patients have improved survival when treated with tyrosine kinase inhibitors compared with chemotherapy.
• Limitations the authors state:
  • Smoking history is often missing from databases, cancer registries and clinical trials. This makes it hard to determine incidence in non-smokers and to evaluate treatment outcomes by smoking status.
  • Environmental exposures such as air pollution are hard to quantify accurately
  • The quality of the evidence was not formally evaluated
  • Some articles may have been missed

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer.

Medical terms in this study, explained in our Lexicon: Lung Cancer, Adenocarcinoma, Small Cell Lung Cancer, EGFR, Somatic Mutation, Dyspnea, Hemoptysis, Low-Dose CT Screening.

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