Never-Smokers With Lung Cancer: Epidemiologic Evidence of a Distinct Disease Entity

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Abstract
Purpose Tobacco smoke is a definite causative agent for lung cancer. It is increasingly being recognized that never-smokers can be afflicted with non–small-cell lung cancer (NSCLC). We aim to assess survival differences between smokers and never-smokers with NSCLC. Patients and Methods We analyzed 975 NSCLC patients who presented from January 1999 to December 2002. Clinical characteristics among current-, former- and never-smokers were tested using χ2 or Kruskal-Wallis test. The hazard ratio (HR) for death and its 95% CI were calculated by Cox regression. Results Of 975 patients, 59 had no smoking history and 33 had no quit time recorded. Of 883 patients analyzed, 286 patients (32.4%) were never-smokers. One hundred ninety-six never-smokers (68.5%) were females compared with 12% among current- and 13% among former-smokers (P < .001). There was a significant difference in histologic subtype between never-smokers and smokers: 69.9% with adenocarcinoma versus 39.9% (current-smokers) versus 47.3% (former-smokers); 5.9% with squamous cell carcinoma versus 35.7% (current-smokers) versus 28% (former-smokers; P < .001). Smokers had significantly poorer performance status (P = .002) and higher median age at diagnosis (P < .001) while more never-smokers presented with advanced disease (P = .002). Eight hundred and five patients (82.6%) died by May 30, 2005. The HR for smokers was significantly higher on both univariate and multivariate analysis (HR, 1.297; 95% CI, 1.040 to 1.619). Conclusion Never-smokers comprised a high proportion of NSCLC patients in Singapore. Definite epidemiologic differences exist between never-smokers and smokers. Differences in survival outcome further suggest that the biology underlying the pathogenesis and behavior of the disease may be different for never-smokers.