Hereditary lung cancer syndrome targets never smokers with germline EGFR gene T790M mutations.
Hereditary lung cancer syndrome targets never smokers with germline EGFR gene T790M mutations.
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DOI：
10.1097/jto.0000000000000130
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发表时间：
2014-04
期刊：
影响因子：
--
通讯作者：
Schiller JH
中科院分区：
文献类型：
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作者：
Gazdar A;Robinson L;Oliver D;Xing C;Travis WD;Soh J;Toyooka S;Watumull L;Xie Y;Kernstine K;Schiller JH
简介遗传性肺癌综合征很少见，表皮生长因子受体 (EGFR) 基因的 T790M 种系突变易导致肺癌的发生。本研究的目的是确定携带这种种系突变的肺癌病例和未受影响的家庭成员的临床特征和吸烟状况，并估计其发病率和外显率。方法我们研究了一个五代以上存在种系 T790M 突变的家庭（14 人），并将我们的观察结果与文献检索获得的数据（15 人）相结合。结果T790M 种系突变发生在大约 1% 的非小细胞肺癌病例中，并且在 7500 名受试者中不到 1 人发生。没有肺癌。散发性和种系 T790M 突变主要是腺癌，倾向于女性，偶尔是多灶性的。在 T790M 种系突变携带者产生的肺癌肿瘤中，73% 含有第二个激活 EGFR 基因突变。继承占主导地位。吸烟的 T790M 种系携带者与从不吸烟的携带者相比，罹患肺癌的优势比为 0.31 (p= 6.0E-05)。与一般肺癌人群相比，患有这种突变的从不吸烟者中患肺癌的比例过高（p = 7.4E-06）。结论种系 T790M 突变导致一种针对从不吸烟者的独特遗传性肺癌综合征，初步估计从不吸烟者携带者患肺癌的风险为 31%，而重度吸烟者的这种风险可能较低。由此产生的癌症与含有散发性 EGFR 突变的肺癌有一些共同特征和差异。
IntroductionHereditary lung cancer syndromes are rare, and T790M germline mutations of the epidermal growth factor receptor (EGFR) gene predispose to the development of lung cancer. The goal of this study was to determine the clinical features and smoking status of lung cancer cases and unaffected family members with this germline mutation and to estimate its incidence and penetrance.MethodsWe studied a family with germline T790M mutations over five generations (14 individuals) and combined our observations with data obtained from a literature search (15 individuals).ResultsT790M germline mutations occurred in approximately 1% of non–small-cell lung cancer cases and in less than one in 7500 subjects without lung cancer. Both sporadic and germline T790M mutations were predominantly adenocarcinomas, favored female gender, and were occasionally multifocal. Of lung cancer tumors arising in T790M germline mutation carriers, 73% contained a second activatingEGFRgene mutation. Inheritance was dominant. The odds ratio that T790M germline carriers who are smokers will develop lung cancer compared with never smoker carriers was 0.31 (p= 6.0E-05). There was an overrepresentation of never smokers with lung cancer with this mutation compared with the general lung cancer population (p= 7.4E-06).ConclusionGermline T790M mutations result in a unique hereditary lung cancer syndrome that targets never smokers, with a preliminary estimate of 31% risk for lung cancer in never smoker carriers, and this risk may be lower for heavy smokers. The resultant cancers share several features and differences with lung cancers containing sporadic EGFR mutations.