Long Exposure of Environmental Tobacco Smoke Associated with Activating EGFR Mutations in Never-Smokers with Non-Small Cell Lung Cancer

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. Clin Cancer Res; 17(1); 39-45. (C) 2010 AACR.