Oncotarget

Research Papers:

EGFR mutation, smoking, and gender in advanced lung adenocarcinoma

Chien-Hua Tseng, Chun-Ju Chiang, Jeng-Sen Tseng, Tsung-Ying Yang, Kuo-Hsuan Hsu, Kun-Chieh Chen, Chih-Liang Wang, Chih-Yi Chen, Sang-Hue Yen, Chun-Ming Tsai, Ming-Shyan Huang, Chao-Chi Ho, Chong-Jen Yu, Ying-Huang Tsai, Jin-Shing Chen, Teh-Ying Chou, Ming-Hsun Tsai, Hsuan-Yu Chen, Kang-Yi Su, Jeremy J.W. Chen, Huei-Wen Chen, Sung-Liang Yu, Tsang-Wu Liu and Gee-Chen Chang _

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Oncotarget. 2017; 8:98384-98393. https://doi.org/10.18632/oncotarget.21842

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Abstract

Chien-Hua Tseng1,2,*, Chun-Ju Chiang2,3,*, Jeng-Sen Tseng4,5, Tsung-Ying Yang4,5, Kuo-Hsuan Hsu6,7, Kun-Chieh Chen4, Chih-Liang Wang8,9, Chih-Yi Chen10,11, Sang-Hue Yen12, Chun-Ming Tsai13, Ming-Shyan Huang14,15, Chao-Chi Ho16, Chong-Jen Yu16,17, Ying-Huang Tsai18,19,20, Jin-Shing Chen17,21,22, Teh-Ying Chou13,23, Ming-Hsun Tsai2,3, Hsuan-Yu Chen24, Kang-Yi Su25,26, Jeremy J.W. Chen7, Huei-Wen Chen27, Sung-Liang Yu25,26,28,29,30, Tsang-Wu Liu31 and Gee-Chen Chang4,5,7,*

1Division of Pulmonary Medicine, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan

2Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan

3Taiwan Cancer Registry, Taipei, Taiwan

4Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan

5Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan

6Division of Critical Care and Respiratory Therapy, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan

7Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan

8Department of Thoracic Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan

9College of Medicine, Chang Gung University, Taoyuan, Taiwan

10Department of Surgery, Chung Shan Medical University Hospital, Taichung, Taiwan

11Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan

12Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan

13Division of Thoracic Oncology, Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

14Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

15School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

16Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

17College of Medicine, National Taiwan University, Taipei, Taiwan

18Department of Pulmonary and Critical Care Medicine, Chiayi Chang Gung Memorial Hospital, Chang Gung Medical Foundation, Puzi, Taiwan

19Department of Respiratory Therapy, Chang Gung University, Taoyuan, Taiwan

20Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan

21Division of Thoracic Surgery, Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan

22Department of Traumatology, National Taiwan University Hospital, Taipei, Taiwan

23Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

24Institute of Statistical Science, Academia Sinica, Taipei, Taiwan

25Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan

26Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan

27Graduate Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan

28NTU Center for Genomic Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan

29Department of Pathology, Graduate Institute of Pathology, College of Medicine, National Taiwan University, Taipei, Taiwan

30Center for Optoelectronic Biomedicine, College of Medicine, National Taiwan University, Taipei, Taiwan

31Institute 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: [email protected]

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.


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