The impact of sex and smoking status on the mutational spectrum of epidermal growth factor receptor gene in non-small cell lung cancer
The impact of sex and smoking status on the mutational spectrum of epidermal growth factor receptor gene in non-small cell lung cancer
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DOI：
10.1158/1078-0432.ccr-07-0216
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发表时间：
2007-10-01
影响因子：
11.5
通讯作者：
Date, Hiroshi
中科院分区：
文献类型：
--
作者：
Toyooka, Shinichi;Matsuo, Keitaro;Date, Hiroshi
目的：表皮生长因子受体（EGFR）基因突变已被报道存在于非小细胞肺癌（NSCLC）中，且与女性和不吸烟状况显著相关。在这项研究中，我们广泛调查了性别和吸烟对EGFR突变的影响。实验设计：我们通过直接测序检查了1467例NSCLC患者的EGFR外显子18至21状态，以研究性别和吸烟状况对EGFR突变谱的影响。结果：在1467例患者中，外显子19有197个突变，外显子21有176个突变，外显子18有21个突变，外显子20有24个突变。为了检验性别和吸烟的独立影响，我们比较了不同性别的吸烟者和不吸烟者以及按吸烟状况分层的男性和女性之间每个外显子的突变状态。在女性中，吸烟者的外显子19 （P = 0.001）和外显子21 （P < 0.001）突变明显低于从不吸烟者。在男性中，吸烟者的外显子19 （P < 0.001）、外显子21 （P < 0.001）和外显子18 （P = 0.003）突变明显低于从不吸烟者。在吸烟分层的分析中，从不吸烟的人在性别上没有差异。然而，吸烟人群中男性外显子19突变的频率明显低于女性（P = 0.003）。此外，以女性不吸烟为参照，男性性别和曾经吸烟状况的交互作用显著降低了外显子19的突变频率（P = 0.047）。结论：性别和吸烟状况均可影响EGFR突变谱。我们的研究结果表明，单个EGFR外显子可能对突变有不同的易感性。
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. 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.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.