Introduction: Approximately, 10-15% of lung cancer patients have never smoked. Previous epidemiological studies on non-tobacco associated lung cancer have been hampered by selected data from a small number of hospitals or limited numbers of patients. By use of data from large population-based registers with national coverage, this study aims to compare characteristics and survival of patients with non-small cell lung cancer (NSCLC) with different smoking histories. Methods: Swedish national population-based registers were used to retrieve data on patients diagnosed with primary NSCLC between 2002 and 2016. The Kaplan-Meier method and Cox proportional hazard models were used to estimate overall survival and lung cancer-specific survival by smoking history. Results: In total, 41,262 patients with NSCLC were included. Of those, 4624 (11%) had never smoked. Never-smokers were more often women and older compared to ever smokers (current and former). Adenocarcinoma was proportionally more common in never-smokers (77%) compared to current (52%) and former smokers (57%). Stage IV disease was more common in neversmokers (57%) than in current (48%) and former smokers (48%). Epidermal growth factor receptor mutation was observed more in never-smokers (37%) compared to current (5%) and former smokers (9%). Both lung cancer-specific and overall survival were higher for never-smokers compared to current smokers. Conclusions: The observed differences in characteristics between never-smokers and smokers, and the higher survival in never-smokers compared to smokers from this large population-based study provide further evidence that lung cancer in never-smokers is clinically different to tobacco-associated lung cancer. The findings from this study emphasise the need for an improved understanding of genetics, pathogenesis, mechanisms and progression of non-tobacco associated lung cancer that may help prevent lung cancer or identify individually targeted treatments. ARTICLE HISTORY

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