The impact of sex and smoking status on the mutational spectrum of epidermal growth factor receptor gene in non-small cell lung cancer

Shinichi Toyooka, Keitaro Matsuo, Hisayuki Shigematsu, Takayuki Kosaka, Masaki Tokumo, Yasushi Yatabe, Syuji Ichihara, Michio Inukai, Hiroshi Suehisa, Junichi Soh, Katsuyuki Kiura, Kwunm Fong, Huei Lee, Ignacio I. Wistuba, Adi F. Gazdar, Tetsuya Mitsudomi, Hiroshi Date

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

Purpose: 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. Experimental Design: 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. Inmales, 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 inmales 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. Conclusion: Both sex and smoking status could influence the EGFR mutational spectrum. Our findings suggest that individual EGFR exons may have differing susceptibilities for mutagenesis.

Original languageEnglish
Pages (from-to)5763-5768
Number of pages6
JournalClinical Cancer Research
Volume13
Issue number19
DOIs
Publication statusPublished - Oct 1 2007
Externally publishedYes

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erbB-1 Genes
Non-Small Cell Lung Carcinoma
Exons
Smoking
Epidermal Growth Factor Receptor
Mutation
Mutagenesis
Sex Characteristics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

The impact of sex and smoking status on the mutational spectrum of epidermal growth factor receptor gene in non-small cell lung cancer. / Toyooka, Shinichi; Matsuo, Keitaro; Shigematsu, Hisayuki; Kosaka, Takayuki; Tokumo, Masaki; Yatabe, Yasushi; Ichihara, Syuji; Inukai, Michio; Suehisa, Hiroshi; Soh, Junichi; Kiura, Katsuyuki; Fong, Kwunm; Lee, Huei; Wistuba, Ignacio I.; Gazdar, Adi F.; Mitsudomi, Tetsuya; Date, Hiroshi.

In: Clinical Cancer Research, Vol. 13, No. 19, 01.10.2007, p. 5763-5768.

Research output: Contribution to journalArticle

Toyooka, S, Matsuo, K, Shigematsu, H, Kosaka, T, Tokumo, M, Yatabe, Y, Ichihara, S, Inukai, M, Suehisa, H, Soh, J, Kiura, K, Fong, K, Lee, H, Wistuba, II, Gazdar, AF, Mitsudomi, T & Date, H 2007, 'The impact of sex and smoking status on the mutational spectrum of epidermal growth factor receptor gene in non-small cell lung cancer', Clinical Cancer Research, vol. 13, no. 19, pp. 5763-5768. https://doi.org/10.1158/1078-0432.CCR-07-0216
Toyooka, Shinichi ; Matsuo, Keitaro ; Shigematsu, Hisayuki ; Kosaka, Takayuki ; Tokumo, Masaki ; Yatabe, Yasushi ; Ichihara, Syuji ; Inukai, Michio ; Suehisa, Hiroshi ; Soh, Junichi ; Kiura, Katsuyuki ; Fong, Kwunm ; Lee, Huei ; Wistuba, Ignacio I. ; Gazdar, Adi F. ; Mitsudomi, Tetsuya ; Date, Hiroshi. / The impact of sex and smoking status on the mutational spectrum of epidermal growth factor receptor gene in non-small cell lung cancer. In: Clinical Cancer Research. 2007 ; Vol. 13, No. 19. pp. 5763-5768.
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T1 - The impact of sex and smoking status on the mutational spectrum of epidermal growth factor receptor gene in non-small cell lung cancer

AU - Toyooka, Shinichi

AU - Matsuo, Keitaro

AU - Shigematsu, Hisayuki

AU - Kosaka, Takayuki

AU - Tokumo, Masaki

AU - Yatabe, Yasushi

AU - Ichihara, Syuji

AU - Inukai, Michio

AU - Suehisa, Hiroshi

AU - Soh, Junichi

AU - Kiura, Katsuyuki

AU - Fong, Kwunm

AU - Lee, Huei

AU - Wistuba, Ignacio I.

AU - Gazdar, Adi F.

AU - Mitsudomi, Tetsuya

AU - Date, Hiroshi

PY - 2007/10/1

Y1 - 2007/10/1

N2 - Purpose: 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. Experimental Design: 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. Inmales, 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 inmales 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. Conclusion: Both sex and smoking status could influence the EGFR mutational spectrum. Our findings suggest that individual EGFR exons may have differing susceptibilities for mutagenesis.

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