Long exposure of environmental tobacco smoke associated with activating EGFR mutations in never-smokers with non-small cell lung cancer

Clin Cancer Res. 2011 Jan 1;17(1):39-45. doi: 10.1158/1078-0432.CCR-10-1773. Epub 2010 Nov 8.

Abstract

Purpose: To examine an association between environmental tobacco smoke (ETS) and activating epidermal growth factor receptor (EGFR) mutations in never-smokers with non-small cell lung cancer (NSCLC).

Experimental design: A total of 126 never-smokers with NSCLC were prospectively included in this study. Detailed ETS information was obtained through a standardized questionnaire including exposure period, place, and duration. Cumulative dose of ETS (CETS) was evaluated as a sum of the number of the exposure years at home and/or workplace. EGFR and K-ras mutations were determined using real-time PCR amplification.

Results: A total of 124 patients (98.4%) had ETS exposure with median CETS of 50 years (range: 0-118). Activating EGFR mutations were detected in 62.7% of the 126 patients and K-ras in 2 of 114 patients. The incidence of activating EGFR mutations was significantly higher in females than in males (67.6% vs. 26.7%; P = 0.002), and increased in quintile groups separated on the basis of CETS (shortest group = 44.0%, longest = 84.6%; P = 0.0033). In the multivariate logistic regression model, including gender, CETS, age, and family history of cancer, both gender and CETS were significantly associated with an incidence of activating EGFR mutations; the odds ratio for the EGFR mutations were 5.13 [95% confidence interval, CI = 1.47-18.0; P = 0.0105] for females and 1.02 (95% CI = 1.00-1.04; P = 0.0193) for each 1-year increment in CETS.

Conclusions: Females and increased ETS exposure are closely associated with EGFR mutations in never-smokers with NSCLC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Non-Small-Cell Lung / chemically induced
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • ErbB Receptors / genetics*
  • Female
  • Humans
  • Logistic Models
  • Lung Neoplasms / chemically induced
  • Lung Neoplasms / genetics*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Mutagenesis / drug effects*
  • Mutation / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tobacco Smoke Pollution / adverse effects*

Substances

  • Tobacco Smoke Pollution
  • ErbB Receptors