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


METHODS
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.
National Hospital Organization Kinki-chuo Chest Medical Center, Osaka, Japan. t-kawaguchi@kch.hosp.go.jp
Tomoya
T
Kawaguchi
Masahiko
M
Ando
Akihito
A
Kubo
Minoru
M
Takada
Shinji
S
Atagi
Kyoichi
K
Okishio
Kazuhiro
K
Asami
Akihide
A
Matsumura
Kazuyuki
K
Tsujino
Ou Sai-Hong
OS
Ignatius
Hidefumi
H
Sasaki
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000139:chemically induced / Q000235:genetics*; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D006801:Humans; D016015:Logistic Models; D008175:Lung Neoplasms / Q000139:chemically induced / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016296:Mutagenesis / Q000187:drug effects*; D009154:Mutation / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*
D014028:Tobacco Smoke Pollution; D066246:ErbB Receptors