EGFR mutation, smoking, and gender in advanced lung adenocarcinoma

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 Chen⁴, Chih-Liang Wang^{8

9}, Chih-Yi Chen^{10

11}, Sang-Hue Yen¹², Chun-Ming Tsai¹³, Ming-Shyan Huang^{14

15}, Chao-Chi Ho¹⁶, 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 Chen²⁴, Kang-Yi Su^{25

26}, Jeremy J W Chen⁷, Huei-Wen Chen²⁷, Sung-Liang Yu^{25

26

28

29

30}, Tsang-Wu Liu³¹, Gee-Chen Chang^{4

5

7}

Affiliations

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.

PMID: 29228697
PMCID: PMC5716737
DOI: 10.18632/oncotarget.21842

EGFR mutation, smoking, and gender in advanced lung adenocarcinoma

Chien-Hua Tseng et al. Oncotarget. 2017.

. 2017 Oct 12;8(58):98384-98393.

doi: 10.18632/oncotarget.21842. eCollection 2017 Nov 17.

Authors

Affiliations

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.

PMID: 29228697
PMCID: PMC5716737
DOI: 10.18632/oncotarget.21842

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.

Keywords: epidermal growth factor receptor (EGFR) mutation; lung adenocarcinoma; overall survival; smoking.

PubMed Disclaimer

Conflict of interest statement

CONFLICTS OF INTEREST There are no conflicts of interest to declare.

Figures

**Figure 1. Duration of overall survival according to the subgroup with or without smoking**
Kaplan-Meier estimates of the duration of overall survival in all advanced lung adenocarcinoma cases (Panel A), in patients with EGFR-wild type (Panel B), and in patients with EGFR mutation (Panel C) are shown. CI, confidence interval.

**Figure 2. Duration of overall survival according to subgroups in terms of *EGFR* mutation status, smoking, and gender**
Kaplan-Meier estimates of the duration of overall survival with regard to EGFR mutation status, smoking, and gender are shown. CI, confidence interval.

See this image and copyright information in PMC

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EGFR mutation, smoking, and gender in advanced lung adenocarcinoma

Affiliations

EGFR mutation, smoking, and gender in advanced lung adenocarcinoma

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

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