title: Divergent epidermal growth factor receptor mutation patterns between smokers and non-smokers with lung adenocarcinoma.
abstract: BACKGROUND
  Smoking status is an important determinant of the prevalence of epidermal growth factor receptor (EGFR) mutations in lung cancer patients. However, it is unclear whether smoking status could also influence the spectrum of EGFR mutations.
  
  
  METHODS
  We enrolled patients with lung adenocarcinoma from three medical centers in Taiwan. EGFR mutations were assessed by Sanger direct sequencing. The objective of this study was to evaluate the influence of smoking status on both the frequency and patterns of EGFR mutations.
  
  
  RESULTS
  From 2001 to 2013, a total of 1175 patients with lung adenocarcinoma were enrolled for EGFR mutation analysis. The overall EGFR mutation rate was 59.6%, which was significantly higher in females than males (69.1% vs. 49.8%) and in non-smokers than current/former smokers (73.8% vs. 29.8%) (both P<0.001). Among patients harboring EGFR mutations, smokers expressed L858R mutation less frequently (35.2% vs. 50.2%, P=0.005) and exon 19 deletions more frequently (52.8% vs 38.8%, P=0.008) than non-smokers. Smokers and non-smokers also had divergent exon 19 deletions subtypes (Del E746-A750 82.5% vs. 57.6%, respectively, P<0.001). Among subgroup patients harboring the L858R mutation, smokers were associated with a higher rate of complex mutations than non-smokers (34.2% vs. 8.4%, P<0.001).
  
  
  CONCLUSIONS
  Our results suggested that smoking status could influence not only the frequency but also the spectrum of EGFR mutations. These findings provide a clue for further investigation of EGFR mutagenesis.
authors.affiliation: Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, No.1650, Sect. 4, Taiwan Boulevard, Taichung 407, Taiwan, ROC.
authors.forename: Jeng-Sen
authors.initials: JS
authors.lastname: Tseng
authors.affiliation: Department of Thoracic Medicine, Chang Gung Memorial Hospital, No. 5, Fu-Hsing St., Kweishan, Taoyuan 333, Taiwan, ROC; College of Medicine, Chang Gung University, Taoyuan, No.259, Wen-Hwa 1st Rd., Kweishan Tao-Yuan, 333, Taiwan, ROC.
authors.forename: Chih-Liang
authors.initials: CL
authors.lastname: Wang
authors.affiliation: Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, No.1650, Sect. 4, Taiwan Boulevard, Taichung 407, Taiwan, ROC; Faculty of Medicine, School of Medicine, National Yang-Ming University, No.155, Sec.2, Linong St., Taipei 112, Taiwan, ROC.
authors.forename: Tsung-Ying
authors.initials: TY
authors.lastname: Yang
authors.affiliation: Institute of Medicine, Division of Thoracic Surgery, Department of Surgery, Chung Shan Medical University, Chung Shan Medical University Hospital, 110, Section 1, Chien-Kuo North Road, Taichung 402, Taiwan, ROC.
authors.forename: Chih-Yi
authors.initials: CY
authors.lastname: Chen
authors.affiliation: Department of Thoracic Medicine, Chang Gung Memorial Hospital, No. 5, Fu-Hsing St., Kweishan, Taoyuan 333, Taiwan, ROC; Department of Respiratory Therapy, College of Medicine, Chang Gung University, Taoyuan, No.259, Wen-Hwa 1st Rd., Kweishan Tao-Yuan, 333, Taiwan, ROC.
authors.forename: Cheng-Ta
authors.initials: CT
authors.lastname: Yang
authors.affiliation: Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, No.1650, Sect. 4, Taiwan Boulevard, Taichung 407, Taiwan, ROC; Institute of Biomedical Sciences, National Chung Hsing University, No.250, Kuo Kuang Rd., Taichung 402, Taiwan, ROC.
authors.forename: Kun-Chieh
authors.initials: KC
authors.lastname: Chen
authors.affiliation: Institute of Biomedical Sciences, National Chung Hsing University, No.250, Kuo Kuang Rd., Taichung 402, Taiwan, ROC; Division of Critical Care and Respiratory Therapy, Department of Internal Medicine, Taichung Veterans General Hospital, No.1650, Sect. 4, Taiwan Boulevard, Taichung 407, Taiwan, ROC.
authors.forename: Kuo-Hsuan
authors.initials: KH
authors.lastname: Hsu
authors.affiliation: Department of Pediatrics, Taichung Veterans General Hospital, No.1650, Sect. 4, Taiwan Boulevard, Taichung 407, Taiwan, ROC; Institute of Molecular Biology, National Chung-Hsing University, No.250, Kuo Kuang Rd., Taichung 402, Taiwan, ROC.
authors.forename: Chi-Ren
authors.initials: CR
authors.lastname: Tsai
authors.affiliation: Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, No.1650, Sect. 4, Taiwan Boulevard, Taichung 407, Taiwan, ROC; Faculty of Medicine, School of Medicine, National Yang-Ming University, No.155, Sec.2, Linong St., Taipei 112, Taiwan, ROC. Electronic address: august@vghtc.gov.tw.
authors.forename: Gee-Chen
authors.initials: GC
authors.lastname: Chang
mesh_terms: D000230:Adenocarcinoma / Q000209:etiology* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D066246:ErbB Receptors / Q000235:genetics*; D005091:Exons; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000209:etiology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D012737:Sex Factors; D012907:Smoking
chemical_list: D066246:ErbB Receptors
keywords: Epidermal growth factor receptor (EGFR) mutation; Lung adenocarcinoma; Lung cancer; Non-small cell lung cancer (NSCLC)