EGFR mutation, smoking, and gender in advanced lung adenocarcinoma

Abstract

// Chien-Hua Tseng 1, 2, * , Chun-Ju Chiang 2, 3, * , Jeng-Sen Tseng 4, 5 , Tsung-Ying Yang 4, 5 , Kuo-Hsuan Hsu 6, 7 , Kun-Chieh Chen 4 , Chih-Liang Wang 8, 9 , Chih-Yi Chen 10, 11 , Sang-Hue Yen 12 , Chun-Ming Tsai 13 , Ming-Shyan Huang 14, 15 , Chao-Chi Ho 16 , Chong-Jen Yu 16, 17 , Ying-Huang Tsai 18, 19, 20 , Jin-Shing Chen 17, 21, 22 , Teh-Ying Chou 13, 23 , Ming-Hsun Tsai 2, 3 , Hsuan-Yu Chen 24 , Kang-Yi Su 25, 26 , Jeremy J.W. Chen 7 , Huei-Wen Chen 27 , Sung-Liang Yu 25, 26, 28, 29, 30 , Tsang-Wu Liu 31 and Gee-Chen Chang 4, 5, 7, * 1 Division of Pulmonary Medicine, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan 2 Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan 3 Taiwan Cancer Registry, Taipei, Taiwan 4 Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan 5 Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan 6 Division of Critical Care and Respiratory Therapy, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan 7 Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan 8 Department of Thoracic Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan 9 College of Medicine, Chang Gung University, Taoyuan, Taiwan 10 Department of Surgery, Chung Shan Medical University Hospital, Taichung, Taiwan 11 Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan 12 Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan 13 Division of Thoracic Oncology, Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan 14 Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan 15 School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan 16 Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan 17 College of Medicine, National Taiwan University, Taipei, Taiwan 18 Department of Pulmonary and Critical Care Medicine, Chiayi Chang Gung Memorial Hospital, Chang Gung Medical Foundation, Puzi, Taiwan 19 Department of Respiratory Therapy, Chang Gung University, Taoyuan, Taiwan 20 Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan 21 Division of Thoracic Surgery, Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan 22 Department of Traumatology, National Taiwan University Hospital, Taipei, Taiwan 23 Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei, Taiwan 24 Institute of Statistical Science, Academia Sinica, Taipei, Taiwan 25 Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan 26 Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan 27 Graduate Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan 28 NTU Center for Genomic Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan 29 Department of Pathology, Graduate Institute of Pathology, College of Medicine, National Taiwan University, Taipei, Taiwan 30 Center for Optoelectronic Biomedicine, College of Medicine, National Taiwan University, Taipei, Taiwan 31 Institute of Cancer Research, National Health Research Institutes, Miaoli, Taiwan * These authors contributed equally to this work as co-first authors Correspondence to: Gee-Chen Chang, email: august@vghtc.gov.tw Keywords: smoking, lung adenocarcinoma, epidermal growth factor receptor (EGFR) mutation, overall survival Received: June 15, 2017      Accepted: September 24, 2017      Published: October 12, 2017 ABSTRACT Purpose: In the current targeted therapy era, information on the effect of smoking in epidermal growth factor receptor ( EGFR )-mutant lung cancer patients is scarce. Results: In total, 11,678 adenocarcinoma patients were enrolled. Of these, 33.3% and 91.8% of male and female patients were non-smokers, respectively. An increased amount of smoking ( P < 0.001 for trend), fewer smoke-free years ( P < 0.001 for trend), and younger age of smoking initiation ( P = 0.034 for trend) were all associated with significantly lower EGFR mutation rates. Smokers had a shorter median overall survival (OS) among both EGFR -mutant and EGFR -wild type patients (17.8 vs. 21.1 months, and 7.9 vs. 11.4 months respectively; both P < 0.001). Among patients with EGFR -mutant adenocarcinoma, younger smokers were associated with shorter OS ( P = 0.047). In multivariate analysis, female gender was an independent prognostic factor for OS (hazard ratio: 0.86 [95% confidence interval {CI}: 0.80–0.93]; P < 0.001 in the EGFR -mutant group and 0.88 [95% CI: 0.81–0.96]; P = 0.004 in the EGFR -wild type group). Materials and Methods: We reviewed the National Lung Cancer database (Taiwan) to assess the impact of smoking on the EGFR mutation rate and survival in advanced lung adenocarcinoma patients during 2011 and 2014 retrospectively. Conclusions: Smoking was associated with lower incidence of EGFR mutation rate and reduced OS of advanced lung adenocarcinoma patients in a dose-dependent manner. In addition to EGFR mutation and smoking, gender also plays an important role in survival among these patients.