Toyooka Shinichi, Matsuo Keitaro, Shigematsu Hisayuki, Kosaka Takayuki, Tokumo Masaki, Yatabe Yasushi, Ichihara Syuji, Inukai Michio, Suehisa Hiroshi, Soh Junichi, Kiura Katsuyuki, Fong Kwun M, Lee Huei, Wistuba Ignacio I, Gazdar Adi F, Mitsudomi Tetsuya, Date Hiroshi
Department of Cancer and Thoracic Surgery, Okayama University, Okayama, Japan.
Clin Cancer Res. 2007 Oct 1;13(19):5763-8. doi: 10.1158/1078-0432.CCR-07-0216.
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.
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.
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.
Both sex and smoking status could influence the EGFR mutational spectrum. Our findings suggest that individual EGFR exons may have differing susceptibilities for mutagenesis.
据报道,表皮生长因子受体(EGFR)基因突变存在于非小细胞肺癌(NSCLC)中,且与女性性别和从不吸烟状态显著相关。在本研究中,我们广泛调查了性别和吸烟对EGFR突变的影响。
我们通过直接测序检测了1467例NSCLC患者的EGFR第18至21外显子状态,以研究性别和吸烟状态对EGFR突变谱的影响。
在1467例患者中,第19外显子发现197个突变,第21外显子176个,第18外显子21个,第20外显子24个。为了研究性别和吸烟的独立作用,比较了每种性别中吸烟者和从不吸烟者之间以及按吸烟状态分层的男性和女性之间每个外显子的突变状态。在女性中,曾经吸烟者中第19外显子(P = 0.001)和第21外显子(P < 0.001)突变的频率明显低于从不吸烟者。在男性中,曾经吸烟者中第19外显子(P < 0.001)、第21外显子(P < 0.001)和第18外显子(P = 0.003)突变的频率明显低于从不吸烟者。在按吸烟分层的分析中,从不吸烟者中性别无差异。然而,在曾经吸烟者中,男性第19外显子突变的频率明显低于女性(P = 0.003)。此外,以女性从不吸烟者为参照时,男性性别与曾经吸烟状态的交互作用显著降低了第19外显子突变的频率(P = 0.047)。
性别和吸烟状态均可影响EGFR突变谱。我们的研究结果表明,EGFR各个外显子对诱变的敏感性可能不同。