International Journal of Clinical Oncology

, Volume 16, Issue 4, pp 287–293 | Cite as

Non-small cell lung cancer in never smokers as a representative ‘non-smoking-associated lung cancer’: epidemiology and clinical features

  • Tokujiro YanoEmail author
  • Akira Haro
  • Yasunori Shikada
  • Riichiroh Maruyama
  • Yoshihiko Maehara
Review Article


Recent interest in lung cancer without a history of tobacco smoking has led to the classification of a distinct disease entity of ‘non-smoking-associated lung cancer’. In this review article, we have made an overview of the recent literature concerning both the epidemiology and clinical features of lung cancer in never smokers, and have brought ‘non-smoking-associated lung cancer’ into relief. The etiology of lung cancer in never smokers remains indefinite although many putative risk factors have been described including secondhand smoking, occupational exposures, pre-existing lung diseases, diet, estrogen exposure, etc. Non-small cell lung cancer (NSCLC) in never smokers is clinically characterized by an increased incidence in females and a higher occurrence of adenocarcinoma in comparison to NSCLC in ever smokers in both surgical patients and non-resectable advanced-stage patients. Furthermore, the prognosis of never-smoking NSCLC is better than that of smoking-related NSCLC in both surgical patients and non-resectable advanced-stage patients. Recently recognized novel gene mutations such as EGFR (epidermal growth factor receptor) mutations are largely limited to never smokers or light smokers, and the expression of this gene is responsible for the clinical efficacy of gefitinib, an epidermal growth factor receptor-tyrosine kinase inhibitor. NSCLC with the EML4 (echinoderm microtubule-associated protein-like 4)-ALK (anaplastic lymphoma kinase) fusion gene is also more likely to occur in never smokers and in those with adenocarcinoma histology, and is expected to benefit from ALK inhibitors. In consideration of the future increase in never-smoking NSCLC or ‘non-smoking-associated lung cancer’, both clinical trials and investigations are needed.


Lung cancer Never smokers Secondhand smoking Estrogen Postoperative survival EGFR mutation 


Conflict of interest

Y. Maehara has received research funding from Chugai Pharmaceutical and AstraZeneca. The others have no conflict of interest.


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Copyright information

© Japan Society of Clinical Oncology 2011

Authors and Affiliations

  • Tokujiro Yano
    • 1
    Email author
  • Akira Haro
    • 1
  • Yasunori Shikada
    • 1
  • Riichiroh Maruyama
    • 1
  • Yoshihiko Maehara
    • 1
  1. 1.Department of Surgery and Science, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan

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