title: The impact of sex and smoking status on the mutational spectrum of epidermal growth factor receptor gene in non small cell lung cancer.
abstract: OBJECTIVE
  Mutation of epidermal growth factor receptor (EGFR) gene has been reported to be present in non-small cell lung cancer (NSCLC) and significantly associated with female sex and never-smoking status. In this study, we extensively investigated the impact of sex and smoking on the EGFR mutation.
  
  
  METHODS
  We examined EGFR exons 18 to 21 status in 1,467 NSCLC patients by direct sequencing to study the impact of sex and smoking status on the EGFR mutational spectrum.
  
  
  RESULTS
  Among 1,467 patients, 197 mutations were found at exon 19, 176 at exon 21, 21 at exon 18, and 24 at exon 20. To examine the independent effect of sex and smoking, the mutational status of each exon was compared between smokers and never smokers in each sex and between males and females stratified by smoking status. In females, exon 19 (P = 0.001) and exon 21 (P < 0.001) mutations were significantly less frequent in ever smokers compared with never smokers. In males, exon 19 (P < 0.001), exon 21 (P < 0.001), and exon 18 (P = 0.003) mutations were significantly less frequent in ever smokers compared with never smokers. In analysis stratified by smoking, there was no difference in sex among never smokers. However, exon 19 mutations were significantly less frequent in males compared with females among ever smokers (P = 0.003). In addition, the interactive effect of male sex and ever smoking status significantly decreased the frequency of exon 19 mutations (P = 0.047) when female never smoker was set as a reference.
  
  
  CONCLUSIONS
  Both sex and smoking status could influence the EGFR mutational spectrum. Our findings suggest that individual EGFR exons may have differing susceptibilities for mutagenesis.
authors.affiliation: Department of Cancer and Thoracic Surgery, Okayama University, Okayama, Japan. toyooka@md.okayama-u.ac.jp
authors.forename: Shinichi
authors.initials: S
authors.lastname: Toyooka
authors.forename: Keitaro
authors.initials: K
authors.lastname: Matsuo
authors.forename: Hisayuki
authors.initials: H
authors.lastname: Shigematsu
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kosaka
authors.forename: Masaki
authors.initials: M
authors.lastname: Tokumo
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Yatabe
authors.forename: Syuji
authors.initials: S
authors.lastname: Ichihara
authors.forename: Michio
authors.initials: M
authors.lastname: Inukai
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Suehisa
authors.forename: Junichi
authors.initials: J
authors.lastname: Soh
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Kiura
authors.forename: Kwun M
authors.initials: KM
authors.lastname: Fong
authors.forename: Huei
authors.initials: H
authors.lastname: Lee
authors.forename: Ignacio I
authors.initials: II
authors.lastname: Wistuba
authors.forename: Adi F
authors.initials: AF
authors.lastname: Gazdar
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Mitsudomi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Date
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism*; D004252:DNA Mutational Analysis; D066246:ErbB Receptors / Q000235:genetics* / Q000502:physiology*; D005091:Exons; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D012737:Sex Factors; D012907:Smoking
chemical_list: D066246:ErbB Receptors