Impact of environmental tobacco smoke on the incidence of mutations in epidermal growth factor receptor gene in never-smoker patients with non-small-cell lung cancer

Purpose: Active tobacco smoking has been associated with the incidence of epidermal growth factor receptor (EGFR) mutations. However, the impact of environmental tobacco smoke (ETS) on EGFR mutations has been unknown. We investigated an association between ETS exposure and EGFR mutations in never smokers with non-small-cell lung cancer (NSCLC). Patients and Methods: We enrolled 179 consecutive never smokers who were newly diagnosed with NSCLC. The history of ETS exposure was obtained with a standardized questionnaire that included exposure period, place, and duration. The nucleotide sequences of exons 18 to 21 on EGFR gene were determined using nested polymerase chain reaction amplification. Results: The incidence of EGFR mutations was significantly lower in patients with ETS exposure than in those without (38.5% v 61.4%; P = .008). In a logistic regression model that adjusted for sex and histology, an adjusted odds ratio (AOR) for the risk of EGFR mutations with exposure to ETS was 0.40 (95% CI, 0.20 to 0.81; P = .011). In quartile groups based on total smoker-year, the AORs for the lowest- to highest-quartile groups were 0.59 (95% CI, 0.23 to 1.49), 0.50 (95% CI, 0.17 to 1.50), 0.48 (95% CI, 0.20 to 1.18), and 0.22 (95% CI, 0.08 to 0.62; P_trend = .028). Among the types of ETS exposure, adulthood ETS and household ETS were significantly associated with the incidence of EGFR mutations. Patients with ETS exposure showed a lower response rate to EGFR tyrosine kinase inhibitors than did patients without ETS exposure (24.6% v 44.8%; P = .053). Conclusion: ETS exposure is negatively associated with EGFR mutations in never smokers with NSCLC.