title: Never-smokers with lung cancer: epidemiologic evidence of a distinct disease entity.
abstract: OBJECTIVE
  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.
  
  
  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 chi2 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medical Oncology, National Cancer Centre, Singapore, Singapore. dmotck@nccs.com.sg
authors.forename: Chee-Keong
authors.initials: CK
authors.lastname: Toh
authors.forename: Fei
authors.initials: F
authors.lastname: Gao
authors.forename: Wan-Teck
authors.initials: WT
authors.lastname: Lim
authors.forename: Swan-Swan
authors.initials: SS
authors.lastname: Leong
authors.forename: Kam-Weng
authors.initials: KW
authors.lastname: Fong
authors.forename: Swee-Peng
authors.initials: SP
authors.lastname: Yap
authors.forename: Anne A L
authors.initials: AA
authors.lastname: Hsu
authors.forename: Philip
authors.initials: P
authors.lastname: Eng
authors.forename: Heng-Nung
authors.initials: HN
authors.lastname: Koong
authors.forename: Agasthian
authors.initials: A
authors.lastname: Thirugnanam
authors.forename: Eng-Huat
authors.initials: EH
authors.lastname: Tan
mesh_terms: D000230:Adenocarcinoma / Q000453:epidemiology* / Q000209:etiology / Q000401:mortality / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology* / Q000209:etiology / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000453:epidemiology* / Q000209:etiology / Q000401:mortality / Q000473:pathology; D008297:Male; D009367:Neoplasm Staging; D012737:Sex Factors; D012907:Smoking / Q000009:adverse effects* / Q000401:mortality; D016019:Survival Analysis