Association of gender and passive smoking with epidermal growth factor receptor mutations in never-smokers with non-small cell lung cancer: A prospective study based on detailed passive smoking questionnaire.

Abstract

7558 Background: Epidermal growth factor receptor (EGFR) mutations occurred frequently in never smokers with non-small cell lung cancer (NSCLC). However, cause of the mutations is unclear. Methods: A total of 126 patients with NSCLC were prospectively included in this study who smoked less than 100 cigarettes during lifetime. Detailed passive smoking information was obtained through questionnaire including exposure period, place (household or work place) and duration. Cumulative dose of passive smoking (CDP) was evaluated as sum of the number of the exposure year per place. EGFR and K-ras mutations were examined using real time polymerase chain reaction amplification (genotyping). Results: One hundred and twenty four patients (98.4%) had the passive smoking history, and the CDP ranged from 0 to 118 (median=50). EGFR mutations were detected in the 83 of 126 patients (36 in-frame deletions in exon 19, 43 mutations in codon 858 in exon 21) and K-ras in the two of 98 patients. The incidence of EGFR mutations was significantly higher in female than in male (70.3%, 33.3%; p = 0.0046), and increased proportionally in the tertile groups separated based on CDP (low group: 56.4%, middle: 60.5%, high: 79.6%; p=0.0250). In the multivariate logistic regression model including gender, CDP and family history of lung cancer, both gender and CDP were significantly associated with the incidence of EGFR mutations; the odds ratio for EGFR mutations were 2.07 (95%CI: 1.17 to 3.85; p = 0.0145) for gender, 1.02 (95%CI: 1.00-1.04; p = 0.0298) for each 1-year increment in CDP, and 1.02 (95%CI: 0.36-3.11; p = 0.9705) for family history of lung cancer. Conclusions: Female gender and longer duration of passive smoking closely associated with epidermal growth factor receptor mutations in never smokers with NSCLC. No significant financial relationships to disclose.