Nonsmall cell lung cancer in never smokers

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Abstract
To summarize the available knowledge about nonsmall cell lung cancer (NSCLC) in never smokers in terms of biological and clinical-pathological findings. Overall in newly diagnosed NSCLC, 10% of men and 20% of women, with a much higher proportion among Asiatic women, are never smokers and among them an overwhelming proportion have adenocarcinoma. Several environmental, genetic, hormonal and viral factors have been associated with an increased risk of NSCLC in never smokers, but for none of them there is definitive evidence. The incidence of epidermal growth factor receptor mutations is higher in never smokers, whereas K-ras mutations are rarely detected in this group of never smoking patients. The role of never smoking status in NSCLC as a positive prognostic factor or predictive of a better chemosensitivity to systemic treatments is still undefined. Epidemiological, molecular and clinical-pathological features indicate NSCLC in never smokers as a distinct entity. Future preclinical studies should address more deeply the biological differences between NSCLC in smokers and never smokers and, to avoid biased results due to differences in survival outcomes, smoking status should be considered among stratification factors in future clinical studies.